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6/28/23, 12:08 AM AMBITION-CM Pathway Feedback Search Clinical Topics Home Studies AMBITION CM AMBITION CM Disease Disease Cryptococcal meningitis Human immunodeficiency virus i Trial question Is single dose liposomal amphotericin B noninferior to WHO recommended treatment for cryptococcal meningitis? Study design Multi-center Open label RCT Population Characteristics of study participants 40.0% female N = 814 60.0% male 814 patients (323 female, 491 male) Inclusion criteria: human immunodeficiency virus positive adults with cryptococcal meningitis Key exclusion criteria: receipt of > 2 doses of either amphotericin or fluconazole before screening; pregnancy or breast-feeding; receipt of contraindicated concomitant drugs; previous adverse reaction to a trial drug Interventions N=407 liposomal amphotericin B (a single high dose of liposomal amphotericin B at 10 mg/kg of body weight on day 1 plus 14 days of flucytosine at 100 mg/kg/day and fluconazole at 1200 mg/day) https://web.pathway.md/studies/rec3hh7085z7GqpRj 1/2 6/28/23, 12:08 AM AMBITION-CM Pathway N=407 WHO recommended treatment (amphotericin B deoxycholate at a dose of 1 mg/kg/day plus flucytosine at 100 mg/kg/day for 7 days, followed by fluconazole at 1200 mg/day for 7 days) Primary outcome Death from any cause at 10 weeks 28.7 % 28.7 24.8 21.5 % 14.3 % Difference not exceeding nonferiority margin 7.2 % 0.0 % Liposomal amphotericin B World Health Organization recommended treatment Difference not exceeding nonferiority margin in death from any cause at 10 weeks (24.8% vs. 28.7%; ARD -4.05, 95% CI -10.2 to 2.1) Secondary outcomes No significant difference in fungal clearance from CSF at day 14 (-0.4 log CFU/ml/day vs. -0.42 log CFU/ml/day; AD 0.017 log CFU/ml/day, 95% CI 0 to 0.04) No significant difference in death from any cause at 4 weeks (17.2% vs. 18.7%; HR 0.92, 95% CI 0.66 to 1.27) No significant difference in death from any cause at 16 weeks (28.3% vs. 29.2%; HR 0.95, 95% CI 0.73 to 1.22) Safety outcomes No significant differences in neutropenia, thrombocytopenia. Significant difference in grade 3 or 4 adverse events (50.0% vs. 62.3%). Conclusion In human immunodeficiency virus positive adults with cryptococcal meningitis, liposomal amphotericin B was noninferior to WHO recommended treatment with respect to death from any cause at 10 weeks. Reference Joseph N Jarvis, David S Lawrence, David B Meya et al. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. N Engl J Med. 2022 Mar 24;386(12):1109-1120. Open reference URL https://web.pathway.md/studies/rec3hh7085z7GqpRj 2/2
6/28/23, 12:08 AM AMBROISIE Pathway Feedback Search Clinical Topics Home Studies AMBROISIE AMBROISIE Trial question Is continued enteral nutrition until extubation noninferior to fasting before extubation in patients in the ICU? Study design Multi-center Open label RCT Population 1130 patients Inclusion criteria: adult patients in receipt of invasive mechanical ventilation for 48 hours in the ICU and prepyloric enteral nutrition for 24 hours at the time of extubation decision Key exclusion criteria: pregnancy; tracheostomy; post-pyloric enterally fed; no affiliation to a social security scheme Interventions N=617 maintenance of calorie intake (continued enteral nutrition until extubation) N=513 maximum gastric vacuity (stopping enteral feeding at least 6 hours before extubation with concomitant gastric suctioning) Primary outcome Rate of extubation failure within 7 days after extubation 17.5 % 17.5 17.2 13.1 % 8.8 % Difference not exceeding nonferiority margin 4.4 % 0.0 % Maintenance of calorie intake Maximum gastric vacuity Difference not exceeding nonferiority margin in the rate of extubation failure within 7 days after extubation (17.2% vs. 17.5%; ARD 0.4, 95% CI -5.2 to 4.5) Secondary outcomes https://web.pathway.md/studies/rec6QKU1FMJcg8zVm 1/2 6/28/23, 12:08 AM AMBROISIE Pathway No significant difference in the rate of pneumonia within 14 days of extubation (1.6% vs. 2.5%; RR 0.77, 95% CI 0.22 to 2.69) Borderline significant decrease in death in the ICU (3.9% vs. 6.8%; RR 0.56, 95% CI 0.32 to 0.99) Borderline significant increase in tachypnea (59% vs. 54%; RR 1.41, 95% CI 1.05 to 1.89) Conclusion In adult patients in receipt of invasive mechanical ventilation for 48 hours in the ICU and prepyloric enteral nutrition for 24 hours at the time of extubation decision, maintenance of calorie intake was noninferior to maximum gastric vacuity with respect to the rate of extubation failure within 7 days after extubation. Reference Micka l Landais, Mai-Anh Nay, Johann Auchabie et al. Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster- randomised, parallel-group, non-inferiority trial. Lancet Respir Med. 2023 Apr;11(4):319-328. Open reference URL https://web.pathway.md/studies/rec6QKU1FMJcg8zVm 2/2
6/28/23, 12:38 AM AMETIS Pathway Feedback Search Clinical Topics Home Studies AMETIS AMETIS Disease Acute ischemic stroke Trial question Is general anesthesia with tracheal intubation superior to procedural sedation in patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke? Study design Multi-center Open label RCT Population Characteristics of study participants 52.0% female N = 273 48.0% male 273 patients (142 female, 131 male) Inclusion criteria: adult patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke Key exclusion criteria: coma or altered vigilance; premorbid disability Interventions N=135 general anesthesia (general anesthesia with tracheal intubation) N=138 procedural sedation (sedation with spontaneous ventilation, targeting minimal to moderate sedation level) Primary outcome https://web.pathway.md/studies/rechwjwQlIfw64JsY 1/2 6/28/23, 12:38 AM AMETIS Pathway Functional independence at day 90 and absence of major periprocedural complications at day 7 36.2 % 36.2 28.2 27.2 % 18.1 % 9.1 % No significant difference 0.0 % General anesthesia Procedural sedation No significant difference in functional independence at day 90 and absence of major periprocedural complications at day 7 (28.2% vs. 36.2%; ARD -8.1, 95% CI -19.1 to 2.3) Secondary outcomes No significant difference in procedure-related serious adverse events (6.7% vs. 3.6%; AD 3%, 95% CI -2.1 to 8.2) No significant difference in excellent recovery at day 90 (14.8% vs. 18.8%; ARD -4, 95% CI -13 to 5) No significant difference in death at day 90 (18.5% vs. 16.7%; AD 2%, 95% CI -7 to 11) Conclusion In adult patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke, general anesthesia was not superior to procedural sedation with respect to functional independence at day 90 and absence of major periprocedural complications at day 7. Reference Russell Chabanne, Thomas Geeraerts, Marc Begard et al. Outcomes After Endovascular Therapy With Procedural Sedation vs General Anesthesia in Patients With Acute Ischemic Stroke: The AMETIS Randomized Clinical Trial. JAMA Neurol. 2023 Apr 3;e230413. Open reference URL https://web.pathway.md/studies/rechwjwQlIfw64JsY 2/2
6/28/23, 12:39 AM AMPLIFY-EXT Pathway Feedback Search Clinical Topics Home Studies AMPLIFY EXT AMPLIFY EXT Disease Disease Deep vein thrombosis Pulmonary embolism Reference Agnelli G, Buller HR, Cohen A et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. Open reference URL https://web.pathway.md/studies/recyW8fVSXRFrdeoZ 1/1
6/28/23, 12:38 AM AMPLIFY Pathway Feedback Search Clinical Topics Home Studies AMPLIFY AMPLIFY Disease Disease Deep vein thrombosis Pulmonary embolism Trial question What is the role of apixaban in patients with acute VTE? Study design Multi-center Double blinded RCT Population Characteristics of study participants 41.0% female N = 5395 59.0% male 5395 patients (2228 female, 3167 male) Inclusion criteria: patients with acute VTE Key exclusion criteria: active bleeding, a high risk of bleeding, or other contraindications to treatment with enoxaparin and warfarin, cancer and long-term treatment with low-molecular- weight heparin was planned, or dual antiplatelet therapy Interventions N=2609 apixaban (10 mg PO BID for 7 days, followed by 5 mg PO BID for 6 months) N=2635 warfarin (subcutaneous enoxaparin, followed by warfarin) Primary outcome Recurrent symptomatic venous thromboembolism or death related to venous thromboembolism https://web.pathway.md/studies/recchDH8YMZNaqn0Y 1/2 6/28/23, 12:38 AM AMPLIFY Pathway 2.7 % 2.7 2.3 2.0 % 1.4 % Difference not exceeding nonferiority margin 0.7 % 0.0 % Apixaban Warfarin Difference not exceeding nonferiority margin in recurrent symptomatic VTE or death related to VTE (2.3% vs. 2.7%; RR 0.84, 95% CI 0.6 to 1.18) Secondary outcomes No significant difference in VTE or death from cardiovascular cause (2.3% vs. 2.9%; RR 0.8, 95% CI 0.57 to 1.11) No significant difference in VTE or death from any cause (3.2% vs. 3.9%; RR 0.82, 95% CI 0.61 to 1.08) Significant decrease in VTE, death related to VTE, or major bleeding (2.8% vs. 4.5%; RR 0.62, 95% CI 0.47 to 0.83) Safety outcomes No significant difference in any adverse event. Significant difference in major bleeding (0.6% vs. 1.8%) and major bleeding plus clinically relevant nonmajor bleeding (4.3% vs. 9.7%). Conclusion In patients with acute VTE, apixaban was noninferior to warfarin with respect to recurrent symptomatic VTE or death related to VTE. Reference Agnelli G, Buller HR, Cohen A et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Open reference URL https://web.pathway.md/studies/recchDH8YMZNaqn0Y 2/2
6/28/23, 12:39 AM ANAHYDRET Pathway Feedback Search Clinical Topics Home Studies ANAHYDRET ANAHYDRET Disease Essential thrombocythemia Trial question Is anagrelide noninferior to hydroxyurea in patients with essential thrombocythemia? Study design Multi-center Single blinded RCT Population Characteristics of study participants 64.0% female N = 259 36.0% male 259 patients (165 female, 93 male) Inclusion criteria: patients with essential thrombocythemia who have high-risk profile Key exclusion criteria: pregnancy, contraindications to the study drugs, known lactose intolerance, severe renal disease, severe liver disease, coexisting malignancy, or systemic diseases Interventions N=122 anagrelide (started at a dose of 1.0 mg/day during the first week and adjusted until maintenance of the platelet count at normal or close to normal levels) N=137 hydroxyurea (started at a dose of 1,500 mg/day and adjusted until maintenance of the platelet count at normal or close to normal levels) Primary outcome https://web.pathway.md/studies/recO6WNolUacnItUm 1/2 6/28/23, 12:39 AM ANAHYDRET Pathway ET-related major and minor thrombohemorrhagic events at 6 months 29.0 events 29 22 21.8 events 14.5 events Difference not exceeding nonferiority margin 7.3 events 0.0 events Anagrelide Hydroxyurea Difference not exceeding nonferiority margin in ET-related major and minor thrombohemorrhagic events at 6 months (22 events vs. 29 events; HR 1.19, 95% CI 0.61 to 2.3) Secondary outcomes No significant difference in ET-related major and minor thrombohemorrhagic events at 12 months (33 events vs. 31 events; HR 1.03, 95% CI 0.57 to 1.81) No significant difference in ET-related events, after 36 months (51 events vs. 47 events; HR 0.92, 95% CI 0.57 to 1.46) No significant difference in the rate of no ET-related thrombotic or bleeding events after observation of up to 6 years (63.9% vs. 67.4%; HR 0.92, 95% CI 0.57 to 1.5) Safety outcomes No significant difference in adverse events and adverse events leading to discontinuation of drugs. Significant differences in anemia (9.0% vs. 18.3%), leukopenia (0.8% vs. 28.2%), palpitations (24.6% vs. 2.3%). Conclusion In patients with essential thrombocythemia who have high-risk profile, anagrelide was noninferior to hydroxyurea with respect to a ET-related major and minor thrombohemorrhagic events at 6 months. Reference Gisslinger H, Gotic M, Holowiecki J et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Open reference URL https://web.pathway.md/studies/recO6WNolUacnItUm 2/2
6/28/23, 12:39 AM ANCHOR Pathway Feedback Search Clinical Topics Home Studies ANCHOR ANCHOR Disease Disease Anal cancer Human immunodeficiency virus i Trial question Is the treatment of anal high-grade squamous intraepithelial lesions superior to active monitoring in patients with increased risk of anal cancer? Study design Multi-center Open label RCT Population Characteristics of study participants 16.7% female N = 4446 83.3% male 4446 patients (711 female, 3575 male) Inclusion criteria: adult patients 35 years of age living with human immunodeficiency virus who had biopsy-proven anal high-grade squamous intraepithelial lesions Key exclusion criteria: history of anal cancer; anal cancer detected at screening; receipt of immunomodulatory investigational agents within 4 weeks of randomization Interventions N=2227 treatment (office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod) N=2219 active-monitoring (examinations for clinical observation every 6 months and biopsy of visible lesions every 12 months) https://web.pathway.md/studies/recYwiFjcK0vSVPTA 1/2 6/28/23, 12:39 AM ANCHOR Pathway Primary outcome Progression to anal cancer 402.0 per 10 402 301.5 per 10 201.0 per 10 173 100.5 per 10 Significant decrease 0.0 per 10 Treatment Active-monitoring Significant decrease in progression to anal cancer (173 per 100,000 p-yrs vs. 402 per 100,000 p- yrs; RR 0.43, 95% CI 0.2 to 0.94) Safety outcomes No significant differences in adverse events, serious adverse events. Conclusion In adult patients 35 years of age living with human immunodeficiency virus who had biopsy- proven anal high-grade squamous intraepithelial lesions, treatment was superior to active- monitoring with respect to progression to anal cancer. Reference Joel M Palefsky, Jeannette Y Lee, Naomi Jay et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022 Jun 16;386(24):2273-2282. Open reference URL https://web.pathway.md/studies/recYwiFjcK0vSVPTA 2/2
6/28/23, 12:41 AM ANDROMEDA-SHOCK Pathway Feedback Search Clinical Topics Home Studies ANDROMEDA SHOCK ANDROMEDA SHOCK Disease Sepsis and septic shock Trial question Is peripheral perfusion-guided resuscitation superior to lactate-guided resuscitation in patients with septic shock? Study design Multi-center Open label RCT Population Characteristics of study participants 53.0% female N = 424 47.0% male 424 patients (226 female, 198 male) Inclusion criteria: patients with septic shock Key exclusion criteria: bleeding, severe ARDS, do-not-resuscitate status, pregnancy Interventions N=212 peripheral perfusion-guided resuscitation N=212 lactate-guided resuscitation Primary outcome Death at 28 days 43.4 % 43.4 https://web.pathway.md/studies/recJUOM5MkhCQDWvH 1/2 6/28/23, 12:41 AM ANDROMEDA-SHOCK Pathway 3 34.9 32.5 % 21.7 % 10.8 % No significant difference 0.0 % Peripheral perfusion-guided resuscitation Lactate-guided resuscitation No significant difference in death at 28 days (34.9% vs. 43.4%; HR 0.75, 95% CI 0.55 to 1.02) Secondary outcomes Significant decrease in SOFA score at 72 hours (5.6 vs. 6.6; MD -1, 95% CI -1.97 to -0.02) Safety outcomes No significant difference in serious adverse events. Conclusion In patients with septic shock, peripheral perfusion-guided resuscitation was not superior to lactate- guided resuscitation with respect to death at 28 days. Reference Hernandez G, Ospina-Tascon GA, Damiani LP et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):654-664. Open reference URL https://web.pathway.md/studies/recJUOM5MkhCQDWvH 2/2
6/28/23, 12:41 AM ANDROMEDA Pathway Feedback Search Clinical Topics Home Studies ANDROMEDA ANDROMEDA Disease Immunoglobulin light chain amyl Trial question What is the role of daratumumab-based treatment in patients with newly diagnosed immunoglobulin light-chain amyloidosis? Study design Multi-center Open label RCT Population Characteristics of study participants 42.0% female N = 388 58.0% male 388 patients (163 female, 225 male) Inclusion criteria: patients with newly diagnosed immunoglobulin light-chain amyloidosis Key exclusion criteria: prior therapy for AL amyloidosis or multiple myeloma, previous or current diagnosis of symptomatic multiple myeloma, significant cardiovascular conditions, eGFR < 20 mL/min/1.73 m of BSA Interventions N=195 daratumumab (six cycles of bortezomib, cyclophosphamide, and dexamethasone with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles) N=193 control (six cycles of bortezomib, cyclophosphamide, and dexamethasone alone) https://web.pathway.md/studies/recdVitryZDdclzkp 1/2 6/28/23, 12:41 AM ANDROMEDA Pathway Primary outcome Hematologic complete response 53.3 % 53.3 40.0 % 26.6 % Significant increase 18.1 13.3 % NNT = 3 0.0 % Daratumumab Control Significant increase in hematologic complete response (53.3% vs. 18.1%; RR 2.9, 95% CI 2.1 to 4.1) Secondary outcomes Significant decrease in major organ deterioration or hematologic progression (17.4% vs. 27.5%; HR 0.58, 95% CI 0.36 to 0.93) Safety outcomes No significant differences in lymphopenia, cardiac failure, diarrhea, death. Conclusion In patients with newly diagnosed immunoglobulin light-chain amyloidosis, daratumumab was superior to control with respect to hematologic complete response. Reference Efstathios Kastritis, Giovanni Palladini, Monique C Minnema et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1;385(1):46-58. Open reference URL https://web.pathway.md/studies/recdVitryZDdclzkp 2/2
6/28/23, 12:41 AM ANGEL-ASPECT Pathway Feedback Search Clinical Topics Home Studies ANGEL ASPECT ANGEL ASPECT Disease Acute ischemic stroke Trial question What is the role of endovascular therapy in patients with acute ischemic stroke with large infarction? Study design Multi-center Open label RCT Population Characteristics of study participants 39.0% female N = 455 61.0% male 455 patients (176 female, 279 male) Inclusion criteria: adult patients, aged 18-80 years, with ischemic stroke within the previous 24 hours Key exclusion criteria: midline shift or clinical signs of herniation; mass effect; high risk of hemorrhage; acute bilateral strokes; or multiple intracranial occlusions Interventions N=230 endovascular therapy (mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty or stenting plus medical management) N=225 medical management (standard guideline-directed medical therapy alone) Primary outcome https://web.pathway.md/studies/recvdo8uV6pEmzKxf 1/2 6/28/23, 12:41 AM ANGEL-ASPECT Pathway Modified Rankin scale score at day 90 4.0 4 4 3.0 2.0 1.0 Significant increase 0.0 Endovascular therapy Medical management Significant increase in mRS score at day 90 (4 vs. 4; OR 1.37, 95% CI 1.11 to 1.69) Secondary outcomes Borderline significant increase in mRS score of 0-2 at day 90 (30% vs. 11.6%; RR 2.62, 95% CI 1.69 to 4.06) Borderline significant increase in mRS score of 0-3 at day 90 (47% vs. 33.3%; RR 1.5, 95% CI 1.17 to 1.91) Borderline significant increase in target artery recanalization at 36 hours (85.8% vs. 36.4%; RR 2.46, 95% CI 1.96 to 3.08) Safety outcomes No significant differences in symptomatic intracranial hemorrhage within 48 hours, death within 90 days, decompressive hemicraniectomy during hospitalization. Significant difference in any intracranial hemorrhage within 48 hours (49.1% vs. 17.3%). Conclusion In adult patients, aged 18-80 years, with ischemic stroke within the previous 24 hours, endovascular therapy was superior to medical management with respect to mRS score at day 90. Reference Xiaochuan Huo, Gaoting Ma, Xu Tong et al. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. N Engl J Med. 2023 Apr 6;388(14):1272-1283. Open reference URL https://web.pathway.md/studies/recvdo8uV6pEmzKxf 2/2
6/28/23, 12:51 AM Annane Trial Pathway Feedback Search Clinical Topics Home Studies Annane Trial Annane Trial Disease Sepsis and septic shock Trial question What is the role of low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock? Study design Multi-center Double blinded RCT Population Characteristics of study participants 33.0% female N = 300 67.0% male 300 patients (100 female, 200 male) Inclusion criteria: patients with septic shock and relative adrenal insufficiency Key exclusion criteria: pregnancy, acute myocardial infarction, PE, advanced form of cancer or AIDS (AIDS) infection, and contraindication or formal indication for corticosteroids Interventions N=151 hydrocortisone and fludrocortisone (hydrocortisone 50 mg IV every 6 hours and fludrocortisone 50 g PO once daily for 7 days) N=149 placebo (matching placebos for 7 days) Primary outcome https://web.pathway.md/studies/recKhC5H3kscRNUjV 1/2 6/28/23, 12:51 AM Annane Trial Pathway Death 63.0 % 63 53 47.3 % 31.5 % Significant decrease 15.8 % NNT = 10 0.0 % Hydrocortisone and fludrocortisone Placebo Significant decrease in death (53% vs. 63%; HR 0.67, 95% CI 0.47 to 0.95) Secondary outcomes Significant increase in the rate of withdrawal of vasopressor therapy within 28 days (57% vs. 40%; HR 1.91, 95% CI 1.29 to 2.84) Safety outcomes No significant difference in adverse events. Conclusion In patients with septic shock and relative adrenal insufficiency, hydrocortisone and fludrocortisone were superior to placebo with respect to death. Reference Annane D, Sebille V, Charpentier C et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. Open reference URL https://web.pathway.md/studies/recKhC5H3kscRNUjV 2/2
6/28/23, 12:41 AM ANRS IPERGAY Pathway Feedback Search Clinical Topics Home Studies ANRS IPERGAY ANRS IPERGAY Disease Human immunodeficiency virus i Trial question What is the role of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men? Study design Multi-center Double blinded RCT Population 400 male patients Inclusion criteria: men who have unprotected anal sex with men and who are at high risk for HIV infection Key exclusion criteria: positive results on testing for HBsAg, chronic infection with HCV, a CrCl < 60 mL/min, an ALT level > 2.5 times the upper limit of the normal range, and glycosuria or proteinuria > 1+ on urine dipstick testing Interventions N=199 truvada (fixed-dose combination of 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine) N=201 placebo (matching placebo pills) Primary outcome Incidence of human immunodeficiency virus 1 infection 6.6/100 py 6.6 4.9/100 py https://web.pathway.md/studies/recjOXLBccB9g5d0g 1/2 6/28/23, 12:41 AM ANRS IPERGAY Pathway 3.3/100 py 1.6/100 py Significant decrease 0.91 0.0/100 py Truvada Placebo Significant decrease in the incidence of human immunodeficiency virus 1 infection (0.91 /100 py vs. 6.6 /100 py; RR 0.14, 95% CI 0.02 to 0.6) Secondary outcomes No significant difference in new STI (41% vs. 33%; RR 1.24, 95% CI -0.24 to 2.72) Significant increase in reduction in sexual partners within the past 2 months (8 vs. 7.5; RR 1.07, 95% CI 0.44 to 1.7) Safety outcomes No significant difference in adverse events and serious adverse events. Significant difference in drug-related gastrointestinal adverse events (14% vs. 5%) and renal adverse events (18% vs. 10%). Conclusion In men who have unprotected anal sex with men and who are at high risk for HIV infection, truvada was superior to placebo with respect to the incidence of human immunodeficiency virus 1 infection. Reference Molina JM, Capitant C, Spire B et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015 Dec 3;373(23):2237-46. Open reference URL https://web.pathway.md/studies/recjOXLBccB9g5d0g 2/2
6/28/23, 12:41 AM ANT-005 TKA (mid-dose) Pathway Feedback Search Clinical Topics Home Studies ANT 005 TKA (mid-dose) ANT 005 TKA (mid-dose) Disease Knee osteoarthritis Trial question Is abelacimab superior to enoxaparin in the prevention of VTE in patients undergoing total knee arthroplasty? Study design Multi-center Open label RCT Population Characteristics of study participants 80.2% female N = 200 19.8% male 200 patients (161 female, 39 male) Inclusion criteria: patients, aged 18-80 years, who were undergoing elective primary unilateral total knee arthroplasty Key exclusion criteria: active bleeding or high risk of bleeding; history of VTE; an eGFR < 60 mL/min/1.73 m2; clinically significant liver disease Interventions N=99 abelacimab (a single intravenous dose of 75 mg once daily) N=101 enoxaparin (a subcutaneous dose of 40 mg once daily) Primary outcome https://web.pathway.md/studies/recybrXeqnbfmW6W0 1/2 6/28/23, 12:41 AM ANT-005 TKA (mid-dose) Pathway Venous thromboembolism 22.0 % 22 16.5 % 11.0 % Significant decrease 5.5 % 5 NNT = 6 0.0 % Abelacimab Enoxaparin Significant decrease in VTE (5% vs. 22%; ARD -16.8, 95% CI -26 to -7.6) Safety outcomes No significant differences in 1 adverse event, major or clinically relevant nonmajor bleeding, frequency of blood transfusions. Conclusion In patients, aged 18-80 years, who were undergoing elective primary unilateral total knee arthroplasty, abelacimab was superior to enoxaparin with respect to VTE. Reference Peter Verhamme, B Alexander Yi, Annelise Segers et al. Abelacimab for Prevention of Venous Thromboembolism. N Engl J Med. 2021 Aug 12;385(7):609-617. Open reference URL https://web.pathway.md/studies/recybrXeqnbfmW6W0 2/2
6/28/23, 12:42 AM ANTHARTIC Pathway Feedback Search Clinical Topics Home Studies ANTHARTIC ANTHARTIC Disease Cardiac arrest Trial question What is the role of preventive short-term antibiotic therapy in patients treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm? Study design Multi-center Double blinded RCT Population Characteristics of study participants 19.4% female N = 198 80.6% male 198 patients (38 female, 156 male) Inclusion criteria: adult patients in ICUs who were being mechanically ventilated after out-of- hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34 C Key exclusion criteria: ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status Interventions N=99 antibiotic (intravenous amoxicillin-clavulanate at doses of 1 g and 200 mg TID for 2 days, starting < 6 hours after the cardiac arrest) N=95 control (intravenous saline TID for 2 days, starting < 6 hours after the cardiac arrest) https://web.pathway.md/studies/recsxizbDgSi8k3VE 1/2 6/28/23, 12:42 AM ANTHARTIC Pathway Primary outcome Early ventilator-associated pneumonia 34.0 % 34 25.5 % 19 17.0 % Significant decrease 8.5 % NNT = 7 0.0 % Antibiotic Control Significant decrease in early ventilator-associated pneumonia (19% vs. 34%; HR 0.53, 95% CI 0.31 to 0.92) Secondary outcomes Significant decrease in the rate of cumulative incidence of ventilator-associated pneumonia on day 5 (17% vs. 31%; HR 0.53, 95% CI 0.3 to 0.95) No significant difference in death at day 28 (41% vs. 37%; AD 4%, 95% CI -10 to 18) Safety outcomes No significant difference in serious adverse events. Significant differences in heart diseases (0.12% vs. 0.06%), respiratory, thoracic, and mediastinal diseases (0.02% vs. 0.08%). Conclusion In adult patients in ICUs who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34 C, antibiotic was superior to control with respect to early ventilator-associated pneumonia. Reference Bruno Fran ois, Alain Cariou, Rapha l Clere-Jehl et al. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. Open reference URL https://web.pathway.md/studies/recsxizbDgSi8k3VE 2/2
6/28/23, 12:52 AM AntibioCor Pathway Feedback Search Clinical Topics Home Studies AntibioCor AntibioCor Disease Disease Alcohol-related liver disease Alcoholic hepatitis Trial question What is the role of prophylactic antibiotics in patients hospitalized with severe alcohol-related hepatitis? Study design Multi-center Double blinded RCT Population Characteristics of study participants 27.0% female N = 284 73.0% male 284 patients (78 female, 206 male) Inclusion criteria: patients hospitalized with severe alcohol-related hepatitis treated with prednisolone Key exclusion criteria: allergy/hypersensitivity to amoxicillin or clavulanic acid; history of liver injury to amoxicillin and/or clavulanic acid; phenylketonuria; severe extrahepatic disease; uncontrolled gastrointestinal bleeding Interventions N=142 amoxicillin-clavulanate (amoxicillin 1 g and clavulanate 125 mg TID plus prednisolone 40 mg/day for 30 days) N=142 placebo (matching placebo TID plus prednisolone 40 mg/day for 30 days) https://web.pathway.md/studies/rec0NMFx3SoIWKVBo 1/2 6/28/23, 12:52 AM AntibioCor Pathway Primary outcome Death from all causes at day 60 21.9 % 21.9 17.3 16.4 % 10.9 % 5.5 % No significant difference 0.0 % Amoxicillin-clavulanate Placebo No significant difference in death from all causes at day 60 (17.3% vs. 21.9%; HR 0.77, 95% CI 0.45 to 1.31) Secondary outcomes No significant difference in death from all causes at day 90 (21% vs. 26.3%; HR 0.78, 95% CI 0.47 to 1.27) Significant decrease in infection at day 60 (29.7% vs. 41.5%; HR 0.62, 95% CI 0.41 to 0.91) No significant difference in hepatorenal syndrome at day 60 (7.7% vs. 8.5%; HR 0.91, 95% CI 0.4 to 2.05) Safety outcomes No significant differences in any serious adverse event, infections, gastrointestinal disorders. Conclusion In patients hospitalized with severe alcohol-related hepatitis treated with prednisolone, amoxicillin- clavulanate was not superior to placebo with respect to death from all causes at day 60. Reference Alexandre Louvet, Julien Labreuche, Thong Dao et al. Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial. JAMA. 2023 May 9;329(18):1558- 1566. Open reference URL https://web.pathway.md/studies/rec0NMFx3SoIWKVBo 2/2
6/28/23, 12:42 AM ANTICIPUSC Pathway Feedback Search Clinical Topics Home Studies ANTICIPUSC ANTICIPUSC Disease Esophageal cancer Trial question What is the role of prophylactic noninvasive ventilation in patients at high-risk of postoperative pulmonary complications? Study design Multi-center Open label RCT Population Characteristics of study participants 20.0% female N = 253 80.0% male 253 patients (50 female, 203 male) Inclusion criteria: patients at high risk of postoperative pulmonary complications after elective or semi-urgent surgery with an Assess Respiratory Risk in Surgical Patients in Catalonia score 45 Key exclusion criteria: obstetrical interventions; pregnancy; surgery under local anesthesia; organ transplantation; outpatient surgery Interventions N=125 prophylactic noninvasive ventilation (intermittent prophylactic face-mask noninvasive ventilation for 6-8 hours/day) N=128 usual postoperative care (standard care after surgery in postoperative unit) https://web.pathway.md/studies/recWg0TKxNKMpudPK 1/2 6/28/23, 12:42 AM ANTICIPUSC Pathway Primary outcome Rate of in-hospital acute respiratory failure within 7 days after surgery 27.3 % 27.3 24 20.5 % 13.7 % 6.8 % No significant difference 0.0 % Prophylactic noninvasive ventilation Usual postoperative care No significant difference in the rate of in-hospital acute respiratory failure within 7 days after surgery (24% vs. 27.3%; OR 0.97, 95% CI 0.9 to 1.04) Secondary outcomes No significant difference in Atelectasis (48.8% vs. 57%; ARD -8.2, 95% CI -21.81 to 5.41) No significant difference in Re-intubation (7.2% vs. 6.3%; AD 0.9%, 95% CI -4.57 to 6.37) Conclusion In patients at high risk of postoperative pulmonary complications after elective or semi-urgent surgery with an Assess Respiratory Risk in Surgical Patients in Catalonia score 45, prophylactic noninvasive ventilation was not superior to usual postoperative care with respect to the rate of in- hospital acute respiratory failure within 7 days after surgery. Reference Stanislas Abrard, Emmanuel Rineau, Valerie Seegers et al. Postoperative prophylactic intermittent noninvasive ventilation versus usual postoperative care for patients at high risk of pulmonary complications: a multicentre randomised trial. Br J Anaesth. 2023 Jan;130(1):e160-e168. Open reference URL https://web.pathway.md/studies/recWg0TKxNKMpudPK 2/2
6/28/23, 12:52 AM Antimicrobial prophylaxis in pancreatoduodenectomy Pathway Feedback Search Clinical Topics Home Studies Antimicrobial prophylaxis in pancreatoduodenectomy Antimicrobial prophylaxis in pancreatoduodenectomy Disease Disease Disease Ampullary cancer Duodenal trauma Neoplastic Trial question Is piperacillin-tazobactam antimicrobial prophylaxis superior to cefoxitin in patients undergoing open pancreatoduodenectomy? Study design Multi-center Open label RCT Population Characteristics of study participants 41.0% female N = 778 59.0% male 778 patients (322 female, 456 male) Inclusion criteria: adults undergoing open pancreatoduodenectomy for any indication Key exclusion criteria: allergies to study medications; active infections; chronic steroid use; significant kidney dysfunction; or pregnancy/breastfeeding Interventions N=378 piperacillin-tazobactam (intravenous infusion of 3.375 or 4.5 g within 60 minutes of incision and every 2-4 hours during operation until incision closing) N=400 cefoxitin (intravenous infusion of 2 g within 60 minutes of incision and every 2-4 hours during operation until incision closing) https://web.pathway.md/studies/recqjPr0tlcAivyCW 1/2 6/28/23, 12:52 AM Antimicrobial prophylaxis in pancreatoduodenectomy Pathway Primary outcome Rate of postoperative surgical site infection within 30 days 32.8 % 32.8 24.6 % 19.8 16.4 % Significant decrease 8.2 % NNT = 8 0.0 % Piperacillin-tazobactam Cefoxitin Significant decrease in the rate of postoperative surgical site infection within 30 days (19.8% vs. 32.8%; OR 0.51, 95% CI 0.38 to 0.68) Secondary outcomes No significant difference in death at day 30 (1.3% vs. 2.5%; OR 0.52, 95% CI 0.14 to 1.93) Significant decrease in postoperative sepsis (4.2% vs. 7.5%; OR 0.55, 95% CI 0.32 to 0.92) Significant decrease in postoperative pancreatic fistula (12.7% vs. 19%; OR 0.62, 95% CI 0.4 to 0.96) Conclusion In adults undergoing open pancreatoduodenectomy for any indication, piperacillin-tazobactam was superior to cefoxitin with respect to the rate of postoperative surgical site infection within 30 days. Reference Michael I D'Angelica, Ryan J Ellis, Jason B Liu et al. Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial. JAMA. 2023 May 9;329(18):1579-1588. Open reference URL https://web.pathway.md/studies/recqjPr0tlcAivyCW 2/2
6/28/23, 12:43 AM APEX Pathway Feedback Search Clinical Topics Home Studies APEX APEX Disease Disease Deep vein thrombosis Pulmonary embolism Trial question What is the role of extended thromboprophylaxis with betrixaban in patients with acute medical illness? Study design Multi-center Double blinded RCT Population Characteristics of study participants 54.0% female N = 7513 46.0% male 7513 patients (4088 female, 3425 male) Inclusion criteria: patients who were hospitalized for acute medical illnesses Key exclusion criteria: unable to receive nourishment by enteral administration, anticipated need for prolonged anticoagulation during the trial, life expectancy < 8 weeks, at risk of increased bleeding, or contraindication to anticoagulation therapy Interventions N=3759 betrixaban (80 mg once daily for 35 to 42 days, plus subcutaneous enoxaparin placebo for 10 +/- 4 days) N=3754 enoxaparin (40 mg once daily SC for 10 +/- 4 days, plus oral betrixaban placebo for 35 to 42 days) https://web.pathway.md/studies/recwBIJivmAM1P9Hx 1/2 6/28/23, 12:43 AM APEX Pathway Primary outcome Asymptomatic proximal deep vein thrombosis and symptomatic venous thromboembolism in patients with an elevated D-dimer level 8.5 % 8.5 6.9 6.4 % 4.3 % 2.1 % Borderline significant decrease 0.0 % Betrixaban Enoxaparin Borderline significant decrease in asymptomatic proximal deep vein thrombosis and symptomatic VTE in patients with an elevated D-dimer level (6.9% vs. 8.5%; RR 0.81, 95% CI 0.65 to 1) Secondary outcomes Significant decrease in the rate of asymptomatic proximal deep vein thrombosis or symptomatic VTE, in patients with an elevated D-dimer level or an age 75 years (5.6% vs. 7.1%; RR 0.8, 95% CI 0.66 to 0.98) Safety outcomes No significant differences in major bleeding (0.7% vs. 0.6%,p=0.55; RR 1.19, 95% CI, 0.67 to 2.12). Conclusion In patients who were hospitalized for acute medical illnesses, betrixaban was superior to enoxaparin with respect to asymptomatic proximal deep vein thrombosis and symptomatic VTE in patients with an elevated D-dimer level. Reference Cohen AT, Harrington RA, Goldhaber SZ et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Open reference URL https://web.pathway.md/studies/recwBIJivmAM1P9Hx 2/2
6/28/23, 12:43 AM APPAC Pathway Feedback Search Clinical Topics Home Studies APPAC APPAC Disease Acute appendicitis Trial question Is antibiotic therapy noninferior to appendectomy in patients with uncomplicated acute appendicitis? Study design Multi-center Open label RCT Population Characteristics of study participants 38.0% female N = 530 62.0% male 530 patients (201 female, 329 male) Inclusion criteria: patients with uncomplicated appendicitis confirmed by a CT scan Key exclusion criteria: complicated appendicitis, age < 18 years or > 60 years, contraindications for CT (eg, pregnancy or lactating, allergy to contrast media or iodine, renal insufficiency with serum creatinine level > 150 mol/L, actively taking metformin), peritonitis, unable to cooperate and provide informed consent, and the presence of serious systemic illness Interventions N=257 antibiotic treatment (ertapenem 1 g IV once daily for 3 days followed by 7 days of levofloxacin 500 mg PO once daily and metronidazole 500 mg TID) N=273 surgical appendectomy (standard open appendectomy) https://web.pathway.md/studies/recscxEzDvDAoYPFv 1/2 6/28/23, 12:43 AM APPAC Pathway Primary outcome Treatment success 99.6 % 99.6 74.7 % 72.7 49.8 % Difference exceeding nonferiority margin 24.9 % 0.0 % Antibiotic treatment Surgical appendectomy Difference exceeding nonferiority margin in treatment success (72.7% vs. 99.6%; ARD -27, 95% CI -31.6 to Infinity) Safety outcomes Significant differences in overall complication rate (2.8% vs. 20.5%, p < 0.001; difference, 17.7%, 95% CI 11.9% to 23.4%). Conclusion In patients with uncomplicated appendicitis confirmed by a CT scan, antibiotic treatment was not noninferior to surgical appendectomy with respect to treatment success. Reference Salminen P, Paajanen H, Rautio T et al. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. JAMA. 2015 Jun 16;313(23):2340-8. Open reference URL https://web.pathway.md/studies/recscxEzDvDAoYPFv 2/2
6/28/23, 12:43 AM APPIC Pathway Feedback Search Clinical Topics Home Studies APPIC APPIC Disease Acute appendicitis Trial question Is a short 2-day course of postoperative antibiotics noninferior to a standard 5-day course in patients with complex appendicitis? Study design Multi-center Open label RCT Population 1005 patients Inclusion criteria: patients, aged 8 years, with complex appendicitis Key exclusion criteria: no informed consent; interval appendectomy; clinical suspicion of severe sepsis; conservative treatment of acute appendicitis; immunocompromised state; pregnancy Interventions N=502 short 2-day course (intravenous cefuroxime/metronidazole 1,500/500 mg TID or ceftriaxone/metronidazole once daily 2,000 mg/TID 500 mg for 48 hours according to local antibiotic policy) N=503 standard 5-day course (intravenous cefuroxime/metronidazole 1,500/500 mg TID or ceftriaxone/metronidazole once daily 2,000 mg/TID 500 mg for 5 days according to local antibiotic policy) Primary outcome Rate of infectious complications and death within 90 days 10.0 % 10 8 7.5 % 5 0 % https://web.pathway.md/studies/reciHWrrVNwnN1c6N 1/2 6/28/23, 12:43 AM APPIC Pathway 5.0 % Difference not exceeding nonferiority margin 2.5 % 0.0 % Short 2-day course Standard 5-day course Difference not exceeding nonferiority margin in the rate of infectious complications and death within 90 days (10% vs. 8%; AD 2%, 95% CI -1.6 to 5.6) Secondary outcomes Borderline significant increase in hospital readmission (12% vs. 6%; OR 2.135, 95% CI 1.34 to 3.4) Borderline significant decrease in adverse effects of antibiotics (9% vs. 22%; OR 0.344, 95% CI 0.24 to 0.5) Conclusion In patients, aged 8 years, with complex appendicitis, short 2-day course was noninferior to standard 5-day course with respect to the rate of infectious complications and death within 90 days. Reference Elisabeth M L de Wijkerslooth, Evert-Jan G Boerma, Charles C van Rossem et al. 2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non- inferiority randomised trial. Lancet. 2023 Jan 17;S0140-6736(22)02588-0. Open reference URL https://web.pathway.md/studies/reciHWrrVNwnN1c6N 2/2
6/28/23, 12:43 AM APROCCHSS Pathway Feedback Search Clinical Topics Home Studies APROCCHSS APROCCHSS Disease Sepsis and septic shock Trial question What is the role of hydrocortisone and fludrocortisone in adult patients with septic shock? Study design Multi-center Double blinded RCT Population Characteristics of study participants 33.0% female N = 1241 67.0% male 1241 patients (415 female, 826 male) Inclusion criteria: patients with septic shock Key exclusion criteria: presence of septic shock for at least 24 hours, a high risk of bleeding, pregnancy or lactation, underlying conditions that could affect short-term survival, or previous treatment with corticosteroids Interventions N=614 hydrocortisone and fludrocortisone (hydrocortisone 50 mg IV q6h plus fludrocortisone 50 g PO/VL daily) N=627 placebo (matching placebo) Primary outcome https://web.pathway.md/studies/recy73JgX1tmzWPTE 1/2 6/28/23, 12:43 AM APROCCHSS Pathway Death at 90 days 49.0 % 49 43 36.8 % 24.5 % Significant decrease 12.3 % NNT = 17 0.0 % Hydrocortisone and fludrocortisone Placebo Significant decrease in death at 90 days (43% vs. 49%; RR 0.88, 95% CI 0.08 to 1.68) Secondary outcomes No significant difference in death at 28 days (34% vs. 39%; RR 0.87, 95% CI 0.75 to 1.01) Significant decrease in ICU mortality (35% vs. 41%; RR 0.86, 95% CI 0.75 to 0.99) Significant decrease in in-hospital mortality (39% vs. 45%; RR 0.86, 95% CI 0.76 to 0.98) Safety outcomes No significant differences in serious adverse events, bleeding, rate or site of superinfection, new- onset sepsis or septic shock, or neurologic sequelae. Significant difference in hyperglycemia (89% vs. 83%). Conclusion In patients with septic shock, hydrocortisone and fludrocortisone were superior to placebo with respect to death at 90 days. Reference Djillali Annane, Alain Renault, Christian Brun-Buisson et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):809-818. Open reference URL https://web.pathway.md/studies/recy73JgX1tmzWPTE 2/2
6/28/23, 12:43 AM APTS Pathway Feedback Search Clinical Topics Home Studies APTS APTS Disease Disease Disease Preterm infant Preterm labor Umbilical Trial question Is delayed cord clamping superior to immediate cord clamping in preterm infants? Study design Multi-center Open label RCT Population Characteristics of study participants 44.0% female N = 1566 56.0% male 1566 patients (683 female, 883 male) Inclusion criteria: fetuses from women who were expected to deliver before 30 weeks of gestation Key exclusion criteria: fetal hemolytic disease; hydrops fetalis; twin-twin transfusion; genetic syndromes; potentially lethal malformations Interventions N=784 delayed cord clamping ( 60 seconds after delivery) N=782 immediate cord clamping ( 10 seconds after delivery) Primary outcome Death or major morbidity at 36 weeks of postmenstrual age 37.2 % 37.2 37 https://web.pathway.md/studies/recgtbxLkoEVLHkEz 1/2 6/28/23, 12:43 AM APTS Pathway 3 % 3 37 27.9 % 18.6 % 9.3 % No significant difference 0.0 % Delayed cord clamping Immediate cord clamping No significant difference in death or major morbidity at 36 weeks of postmenstrual age (37% vs. 37.2%; RR 1, 95% CI 0.88 to 1.13) Secondary outcomes Significant decrease in death at 36 weeks (6.4% vs. 9%; RR 0.69, 95% CI 0.49 to 0.97) No significant difference in death or severe brain injury (13.6% vs. 15.3%; RR 0.85, 95% CI 0.67 to 1.08) No significant difference in chronic lung disease (54.4% vs. 51.6%; RR 1.04, 95% CI 0.95 to 1.14) Conclusion In fetuses from women who were expected to deliver before 30 weeks of gestation, delayed cord clamping was not superior to immediate cord clamping with respect to death or major morbidity at 36 weeks of postmenstrual age. Reference William Tarnow-Mordi, Jonathan Morris, Adrienne Kirby et al. Delayed versus Immediate Cord Clamping in Preterm Infants. N Engl J Med. 2017 Dec 21;377(25):2445-2455. Open reference URL https://web.pathway.md/studies/recgtbxLkoEVLHkEz 2/2
6/28/23, 12:43 AM APW-RSV-II Pathway Feedback Search Clinical Topics Home Studies APW RSV II APW RSV II Disease Bronchiolitis Trial question What is the role of azithromycin in children hospitalized with recurrent syncytial virus bronchiolitis? Study design Single center Double blinded RCT Population Characteristics of study participants 45.5% female N = 200 54.5% male 200 patients (91 female, 109 male) Inclusion criteria: healthy 1 to 18 months old children hospitalized with RSV bronchiolitis Key exclusion criteria: prematurity; history or presence of other significant diseases; history of previous wheeze or previous treatment with albuterol; significant developmental delay; failure to thrive Interventions N=101 azithromycin (oral suspension of 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days) N=99 placebo (placebo suspension) Primary outcome https://web.pathway.md/studies/recYCoNyA01KN09Cm 1/2 6/28/23, 12:43 AM APW-RSV-II Pathway Percentage of patients who developed recurrent wheeze 47.0 % 47 36 35.3 % 23.5 % 11.8 % No significant difference 0.0 % Azithromycin Placebo No significant difference in the percentage of patients who developed recurrent wheeze (47% vs. 36%; HR 1.45, 95% CI 0.92 to 2.29) Secondary outcomes No significant difference in the incidence of respiratory symptoms (26.2 days/year vs. 22.2 days/year; RR 1.18, 95% CI 0.86 to 1.62) No significant difference in the incidence of albuterol use (4 days/year vs. 3.3 days/year; RR 1.22, 95% CI 0.6 to 2.48) No significant difference in asthma diagnosis by the end of data collection (15.6% vs. 8.7%; HR 1.95, 95% CI 0.83 to 4.61) Safety outcomes No significant difference in serious adverse events. Conclusion In healthy 1 to 18 months old children hospitalized with RSV bronchiolitis, azithromycin was not superior to placebo with respect to the percentage of patients who developed recurrent wheeze. Reference Avraham Beigelman, M.D., Mythili Srinivasan et al. Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis. NEJM Evid. 2022;1(4). Open reference URL https://web.pathway.md/studies/recYCoNyA01KN09Cm 2/2
6/28/23, 12:43 AM ARAIS Pathway Feedback Search Clinical Topics Home Studies ARAIS ARAIS Disease Acute ischemic stroke Trial question What is the role of argatroban plus intravenous alteplase in patients with acute ischemic stroke? Study design Multi-center Open label RCT Population Characteristics of study participants 29.1% female N = 696 70.9% male 696 patients (238 female, 579 male) Inclusion criteria: adult patients with acute ischemic stroke who were assigned within 4.5 hours of symptom onset Key exclusion criteria: presence of disability in the community before the stroke; history of intracerebral hemorrhage; gastrointestinal or urinary tract bleeding in the last 30 days; need for concomitant use of anticoagulants other than argatroban Interventions N=329 argatroban plus alteplase (intravenous argatroban within 1 hour after intravenous alteplase) N=367 alteplase alone (intravenous alteplase) https://web.pathway.md/studies/receXbbrp6p1NU5PF 1/2 6/28/23, 12:43 AM ARAIS Pathway Primary outcome Excellent functional outcome at day 90 64.9 % 64.9 63.8 48.7 % 32.5 % 16.2 % No significant difference 0.0 % Argatroban plus alteplase Alteplase alone No significant difference in excellent functional outcome at day 90 (63.8% vs. 64.9%; RR 0.98, 95% CI 0.88 to 1.1) Secondary outcomes No significant difference in mRS score of 0-2 within 90 (76% vs. 76.3%; RR 1, 95% CI 0.92 to 1.08) No significant difference in early neurologic improvement within 48 hours (69% vs. 67.9%; RR 1.03, 95% CI 0.84 to 1.27) No significant difference in early neurologic deterioration within 48 hours (3.6% vs. 5.1%; RR 0.71, 95% CI 0.36 to 1.4) Safety outcomes No significant difference in symptomatic intracranial hemorrhage; parenchymal hematoma type 2; major systemic bleeding. Conclusion In adult patients with acute ischemic stroke who were assigned within 4.5 hours of symptom onset, argatroban plus alteplase was not superior to alteplase alone with respect to excellent functional outcome at day 90. Reference Hui-Sheng Chen, Yu Cui, Zhong-He Zhou et al. Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial. JAMA. 2023 Feb 9;e230550. Open reference URL https://web.pathway.md/studies/receXbbrp6p1NU5PF 2/2
6/28/23, 12:43 AM ARDSNet Pathway Feedback Search Clinical Topics Home Studies ARDSNet ARDSNet Disease Acute respiratory distress syndr Trial question Is ventilation with lower tidal volumes superior to traditional tidal volume in patients with ARDS? Study design Multi-center Open label RCT Population Characteristics of study participants 41.0% female N = 861 59.0% male 861 patients (349 female, 512 male) Inclusion criteria: patients with ARDS and acute lung injury Key exclusion criteria: younger than 18 years of age; pregnancy; increased ICP, neuromuscular disease that could impair spontaneous breathing, sickle cell disease, or severe chronic respiratory disease; bone marrow or lung transplantation; chronic liver disease Interventions N=432 ventilation with lower tidal volumes (initial tidal volume of 6 mL/kg of predicted body weight and a plateau pressure 30 cmH O) N=429 traditional tidal volume (initial tidal volume of 12 mL/kg of predicted body weight and plateau pressure 50 cmH O) https://web.pathway.md/studies/reciLDwFqOMCg3XGM 1/2 6/28/23, 12:43 AM ARDSNet Pathway Primary outcome Hospital death 39.8 % 39.8 31 29.8 % 19.9 % Significant decrease 9.9 % NNT = 11 0.0 % Ventilation with lower tidal volumes Traditional tidal volume Significant decrease in hospital death (31% vs. 39.8%; RR 0.78, 95% CI 2.4 to 15.3) Secondary outcomes Significant increase in ventilator-free days at 28 days (12 days vs. 10 days; ARD 2, 95% CI 0.55 to 3.45) Conclusion In patients with ARDS and acute lung injury, ventilation with lower tidal volumes were superior to traditional tidal volume with respect to hospital death. Reference Brower RG, Matthay MA, Morris A et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. Open reference URL https://web.pathway.md/studies/reciLDwFqOMCg3XGM 2/2
6/28/23, 12:45 AM AReSVi-006 Pathway Feedback Search Clinical Topics Home Studies AReSVi-006 AReSVi-006 Disease Bronchiolitis Trial question What is the role of RSV prefusion F protein vaccine in older adults? Study design Multi-center Double blinded RCT Population Characteristics of study participants 52.0% female N = 24966 48.0% male 24966 patients (12915 female, 12051 male) Inclusion criteria: adults 60 years of age Key exclusion criteria: serious or unstable chronic disease; immunosuppression; history of reaction/hypersensitivity by any component of vaccine; recurrent/uncontrolled neurological disorders or seizures Interventions N=12467 RSVPreF3 OA vaccine (a single dose of an AS01E-adjuvanted RSV prefusion F protein- based candidate vaccine before RSV season) N=12499 placebo vaccine (matching placebo vaccine before RSV season) Primary outcome https://web.pathway.md/studies/recNxftENGhsVP9Y2 1/2 6/28/23, 12:45 AM AReSVi-006 Pathway Respiratory syncytial virus-related lower respiratory tract disease 5.8/1000 pt-y 5.8 4.3/1000 pt-y 2.9/1000 pt-y 1.4/1000 pt-y Significant decrease 1 0.0/1000 pt-y RSVPreF3 OA vaccine Placebo vaccine Significant decrease in RSV-related lower respiratory tract disease (1 per 1,000 participant-years vs. 5.8 per 1,000 participant-years; AD -4.8 per 1,000 participant-years, 95% CI 62.4 to 99.9) Secondary outcomes No significant difference in RSV-related acute respiratory infection (3.9 per 1,000 participant-years vs. 13.9 per 1,000 participant-years; AD -10 per 1,000 participant-years, 95% CI -20.02 to 0.02) No significant difference in RSV type A-related lower respiratory tract disease (0.3 per 1,000 participant-years vs. 1.9 per 1,000 participant-years; AD -1.6 per 1,000 participant-years, 95% CI -3.2 to 0) Safety outcomes No significant difference in serious adverse events and potential immune-mediated diseases. Significant difference in any solicited reaction (72% vs. 28%). Conclusion In adults 60 years of age, RSVPreF3 OA vaccine was superior to placebo vaccine with respect to RSV-related lower respiratory tract disease. Reference Alberto Papi, Michael G Ison, Joanne M Langley et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med. 2023 Feb 16;388(7):595-608. Open reference URL https://web.pathway.md/studies/recNxftENGhsVP9Y2 2/2
6/28/23, 12:44 AM ARISE Pathway Feedback Search Clinical Topics Home Studies ARISE ARISE Disease Sepsis and septic shock Trial question What is the role of early goal-directed therapy in critically ill patients with early septic shock? Study design Multi-center Open label RCT Population Characteristics of study participants 40.4% female N = 1600 59.6% male 1600 patients (641 female, 950 male) Inclusion criteria: patients presenting to the emergency department with early septic shock Key exclusion criteria: age < 18 years, contraindication to central venous catheter insertion in the superior vena cava, contraindication to receiving blood products, hemodynamic instability due to active bleeding, underlying disease process with a life expectancy < 90 days, death deemed imminent and inevitable, confirmed or suspected pregnancy Interventions N=796 early goal-directed therapy (in the first 6 hour period) N=804 standard of care (in the first 6 hour period) Primary outcome https://web.pathway.md/studies/recsYafocutxooYu1 1/2 6/28/23, 12:44 AM ARISE Pathway Death at 90 days 18.8 % 18.8 18.6 14.1 % 9.4 % 4.7 % No significant difference 0.0 % Early goal-directed therapy Standard of care No significant difference in death at 90 days (18.6% vs. 18.8%; RR 0.98, 95% CI 0.8 to 1.21) Secondary outcomes No significant difference in death at 28 days (14.8% vs. 15.9%; RR 0.93, 95% CI 0.73 to 1.17) Safety outcomes No significant differences in 1 adverse events (7.1% vs. 5.3%, p=0.15). Conclusion In patients presenting to the emergency department with early septic shock, early goal-directed therapy was not superior to standard of care with respect to death at 90 days. Reference ARISE Investigators, ANZICS Clinical Trials Group, Peake SL et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. Open reference URL https://web.pathway.md/studies/recsYafocutxooYu1 2/2
6/28/23, 12:44 AM ARISTOTLE Pathway Feedback Search Clinical Topics Home Studies ARISTOTLE ARISTOTLE Disease Disease Disease Acute ischemic stroke Atrial fibrillation Transient Trial question What is the role of apixaban in patients with AF? Study design Multi-center Double blinded RCT Population Characteristics of study participants 35.0% female N = 18201 65.0% male 18201 patients (6416 female, 11785 male) Inclusion criteria: patients with AF and at least one additional risk factor for stroke Key exclusion criteria: AF due to a reversible cause, moderate or severe mitral stenosis, conditions other than AF that required anticoagulation (e.g., a prosthetic heart valve), stroke within the previous 7 days, need for aspirin at a dose of > 165 mg a day or for both aspirin and clopidogrel, and severe renal insufficiency Interventions N=9120 apixaban (5 mg PO BID) N=9081 warfarin (dose-adjusted, with target INR 2.0 to 3.0) Primary outcome https://web.pathway.md/studies/recIQaJuFFnfVC1ki 1/2 6/28/23, 12:44 AM ARISTOTLE Pathway Incidence of ischemic or hemorrhagic stroke or systemic embolism 1.6 % / y 1.6 1.2 % / y 1.2 0.8 % / y 0.4 % / y Significant decrease 0.0 % / y Apixaban Warfarin Significant decrease in the incidence of ischemic or hemorrhagic stroke or systemic embolism (1.2% / y vs. 1.6% / y; HR 0.79, 95% CI 0.66 to 0.95) Secondary outcomes Significant decrease in the incidence of major bleeding (2.13% / y vs. 3.09% / y; HR 0.69, 95% CI 0.6 to 0.8) Significant decrease in death from any cause (3.52% vs. 3.94%; HR 0.89, 95% CI 0.8 to 0.99) Significant decrease in the incidence of hemorrhagic stroke (0.24% / y vs. 0.47% / y; HR 0.51, 95% CI 0.35 to 0.75) Safety outcomes No significant difference in adverse events (81.5% vs. 83.1%) and serious adverse events (35.0% vs. 36.5%). Conclusion In patients with AF and at least one additional risk factor for stroke, apixaban was superior to warfarin with respect to the incidence of ischemic or hemorrhagic stroke or systemic embolism. Reference Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. Open reference URL https://web.pathway.md/studies/recIQaJuFFnfVC1ki 2/2
6/28/23, 12:44 AM ARRIVE (aspirin) Pathway Feedback Search Clinical Topics Home Studies ARRIVE (aspirin) ARRIVE (aspirin) Disease Disease Disease Acute ischemic stroke Non-ST-elevation myocardial inf ST-elevat Trial question What is the role of aspirin in the primary prevention of cardiovascular events in patients at moderate risk of CVD? Study design Multi-center Double blinded RCT Population Characteristics of study participants 30.0% female N = 12546 70.0% male 12546 patients (3703 female, 8838 male) Inclusion criteria: patients with a moderate estimated risk of a first cardiovascular event Key exclusion criteria: high risk of gastrointestinal bleeding or other bleeding, diabetes, history of a vascular event, such as stroke, myocardial infarction, coronary artery angioplasty or stenting, coronary artery bypass graft, congestive HF, or vascular intervention Interventions N=6270 aspirin (100 mg PO once daily daily) N=6276 placebo (matching tablet once daily) Primary outcome https://web.pathway.md/studies/recCbUafZfWtiBOCn 1/2 6/28/23, 12:44 AM ARRIVE (aspirin) Pathway Myocardial infarction, stroke, cardiovascular death, unstable angina, or transient ischemic attack 4.5 % 4.48 4.29 3.4 % 2.2 % 1.1 % No significant difference 0.0 % Aspirin Placebo No significant difference in myocardial infarction, stroke, cardiovascular death, unstable angina, or TIA (4.29% vs. 4.48%; HR 0.96, 96% CI 0.81 to 1.13) Secondary outcomes No significant difference in fatal or nonfatal myocardial infarction in the intention-to-treat population (1.52% vs. 1.78%; HR 0.85, 95% CI 0.64 to 1.11) No significant difference in in the intention-to-treat population, nonfatal myocardial infarction (1.4% vs. 1.56%; HR 0.9, 95% CI 0.67 to 1.2) No significant difference in death, in the intention-to-treat population (2.55% vs. 2.57%; HR 0.99, 99% CI 0.8 to 1.24) Safety outcomes No significant difference in overall adverse events (82.01% vs. 81.72%). Significant differences in overall incidence of treatment-related adverse events (16.75% vs. 13.54%, p<0.0001), and gastrointestinal bleeding events (0.97% vs. 0.46%, p = 0.0007). Conclusion In patients with a moderate estimated risk of a first cardiovascular event, aspirin was not superior to placebo with respect to myocardial infarction, stroke, cardiovascular death, unstable angina, or TIA. Reference Gaziano JM, Brotons C, Coppolecchia R et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018 Sep 22;392(10152):1036-1046. Open reference URL https://web.pathway.md/studies/recCbUafZfWtiBOCn 2/2
6/28/23, 12:45 AM ARRIVE (labor) Pathway Feedback Search Clinical Topics Home Studies ARRIVE (labor) ARRIVE (labor) Disease Induction of labor Trial question Is labor induction superior to expectant management in low-risk nulliparous women? Study design Multi-center Open label RCT Population 6106 female patients Inclusion criteria: low-risk nulliparous women between 38 weeks 0 days to 38 weeks 6 days of gestation Key exclusion criteria: plan for cesarean delivery or contraindication to labor; signs of labor; fetal demise; premature rupture of membranes; vaginal bleeding Interventions N=3062 labor induction (induction of labor at 39 weeks 0 days to 39 weeks 4 days) N=3044 expectant management (elective delivery before 40 weeks 5 days and delivery initiated no later than 42 weeks 2 days) Primary outcome Perinatal death or severe neonatal complications 5.4 % 5.4 4.3 4.1 % 2.7 % Significant decrease 1.4 % NNT = 91 0 0 % https://web.pathway.md/studies/rec1b2DSXOiZbOrTa 1/2 6/28/23, 12:45 AM ARRIVE (labor) Pathway 0.0 % Labor induction Expectant management Significant decrease in perinatal death or severe neonatal complications (4.3% vs. 5.4%; RR 0.8, 95% CI 0.64 to 1) Secondary outcomes Significant decrease in cesarean delivery (18.6% vs. 22.2%; RR 0.84, 95% CI 0.76 to 0.93) Significant decrease in hypertensive disorders of pregnancy (9.1% vs. 14.1%; RR 0.64, 95% CI 0.56 to 0.74) No significant difference in neonatal intermediate or ICU admission (11.7% vs. 13%; RR 0.9, 95% CI 0.79 to 1.03) Conclusion In low-risk nulliparous women between 38 weeks 0 days to 38 weeks 6 days of gestation, labor induction was superior to expectant management with respect to perinatal death or severe neonatal complications. Reference William A Grobman, Madeline M Rice, Uma M Reddy et al. Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. N Engl J Med. 2018 Aug 9;379(6):513-523. Open reference URL https://web.pathway.md/studies/rec1b2DSXOiZbOrTa 2/2
6/28/23, 12:45 AM ASCEMBL Pathway Feedback Search Clinical Topics Home Studies ASCEMBL ASCEMBL Disease Chronic myeloid leukemia Trial question What is the role of asciminib in patients with chronic-phase chronic myeloid leukemia previously treated with 2 TKIs? Study design Multi-center Open label RCT Population Characteristics of study participants 52.0% female N = 233 48.0% male 233 patients (120 female, 113 male) Inclusion criteria: adult patients with chronic-phase chronic myeloid leukemia previously treated with 2 TKIs Key exclusion criteria: cardiac or cardiac repolarization abnormality; uncontrolled diabetes; pulmonary hypertension; acute or chronic liver disease; history of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis Interventions N=157 asciminib (at a dose of 40 mg BID) N=76 bosutinib (at a dose of 500 mg once daily) https://web.pathway.md/studies/recFyTiRHWC24ftsO 1/2 6/28/23, 12:45 AM ASCEMBL Pathway Primary outcome Major molecular response rate at week 24 25.5 % 25.5 19.1 % 13.2 12.8 % Significant increase 6.4 % NNT = 8 0.0 % Asciminib Bosutinib Significant increase in major molecular response rate at week 24 (25.5% vs. 13.2%; AD 12.2%, 95% CI 2.19 to 22.3) Secondary outcomes Significant increase in major molecular response rate at week 96 (37.6% vs. 15.8%; AD 21.74%, 95% CI 10.53 to 32.95) Significant increase in complete cytogenic response rate at week 96 (39.8% vs. 16.1%; AD 23.9%, 95% CI 10.3 to 37.4) Safety outcomes No significant difference in adverse events. Conclusion In adult patients with chronic-phase chronic myeloid leukemia previously treated with 2 TKIs, asciminib was superior to bosutinib with respect to major molecular response rate at week 24. Reference Andreas Hochhaus, Delphine R a, Carla Boquimpani et al. Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia. 2023 Mar;37(3):617-626. Open reference URL https://web.pathway.md/studies/recFyTiRHWC24ftsO 2/2
6/28/23, 12:45 AM ASCEND (aspirin) Pathway Feedback Search Clinical Topics Home Studies ASCEND (aspirin) ASCEND (aspirin) Disease Disease Diabetes mellitus type 1 Diabetes mellitus type 2 Trial question What is the effect of aspirin for the prevention of first cardiovascular events in adult diabetic patients? Study design Multi-center Single blinded RCT Population Characteristics of study participants 37.0% female N = 15480 63.0% male 15480 patients (5796 female, 9684 male) Inclusion criteria: adult diabetic patients with no evident CVD Key exclusion criteria: clear indication for aspirin; contraindication to aspirin; known CVD; presence of other clinically significant conditions that might limit adherence to the trial regimen for at least 5 years Interventions N=7740 aspirin (100 mg PO once daily) N=7740 placebo (matching oral tablet once daily) Primary outcome https://web.pathway.md/studies/recRsJAL9vMtCcBix 1/2 6/28/23, 12:45 AM ASCEND (aspirin) Pathway Rate of serious vascular events at a mean follow-up of 7.4 years 9.6 % 9.6 8.5 7.2 % 4.8 % Significant decrease 2.4 % NNT = 91 0.0 % Aspirin Placebo Significant decrease in the rate of serious vascular events at a mean follow-up of 7.4 years (8.5% vs. 9.6%; RR 0.88, 95% CI 0.79 to 0.97) Secondary outcomes Significant increase in major bleeding events (4.1% vs. 3.2%; RR 1.29, 95% CI 1.09 to 1.52) Safety outcomes No significant differences in gastrointestinal tract cancer, any cancers excluding nonfatal nonmelanoma skin cancer. Conclusion In adult diabetic patients with no evident CVD, aspirin was superior to placebo with respect to the rate of serious vascular events at a mean follow-up of 7.4 years. Reference ASCEND Study Collaborative Group, Bowman L, Mafham M et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018 Oct 18;379(16):1529-1539. Open reference URL https://web.pathway.md/studies/recRsJAL9vMtCcBix 2/2
6/28/23, 12:45 AM ASCEND (pirfenidone) Pathway Feedback Search Clinical Topics Home Studies ASCEND (pirfenidone) ASCEND (pirfenidone) Disease Idiopathic pulmonary fibrosis Trial question What is the role of pirfenidone in patients with idiopathic pulmonary fibrosis? Study design Multi-center Open label RCT Population Characteristics of study participants 22.0% female N = 555 78.0% male 555 patients (120 female, 435 male) Inclusion criteria: patients with idiopathic pulmonary fibrosis Key exclusion criteria: history of malignancy, severe hepatic impairment, end-stage renal disease, unstable deteriorating cardiac or pulmonary disease, pregnancy or lactation, or history of alcohol or substance abuse in the past 2 years Interventions N=278 pirfenidone (2403 mg PO per day for 52 weeks) N=277 placebo (matching placebo PO for 52 weeks) Primary outcome Death or a 10% decline in forced vital capacity at 52 weeks https://web.pathway.md/studies/recuVcgroYmfYZNQj 1/2 6/28/23, 12:45 AM ASCEND (pirfenidone) Pathway 31.8 % 31.8 23.9 % 16.5 15.9 % Significant decrease 8.0 % NNT = 7 0.0 % Pirfenidone Placebo Significant decrease in death or a 10% decline in FVC at 52 weeks (16.5% vs. 31.8%; RR 0.52, 95% CI 0.21 to 0.83) Secondary outcomes Significant decrease in change in 6-minute walk distance or death at 52 weeks (25.9% vs. 35.7%; RR 0.73, 95% CI 0.03 to 1.43) No significant difference in death from any cause (4% vs. 7.2%; HR 0.55, 95% CI 0.26 to 1.15) Safety outcomes Significant difference in grade 3 GI adverse events (5.4% vs. 1.4%) and grade 3 skin-related adverse events (1.8% vs. 0.4%). Conclusion In patients with idiopathic pulmonary fibrosis, pirfenidone was superior to placebo with respect to death or a 10% decline in FVC at 52 weeks. Reference King TE Jr, Bradford WZ, Castro-Bernardini S et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. Open reference URL https://web.pathway.md/studies/recuVcgroYmfYZNQj 2/2
6/28/23, 12:45 AM ASPIRE Pathway Feedback Search Clinical Topics Home Studies ASPIRE ASPIRE Disease Disease Deep vein thrombosis Pulmonary embolism Trial question What is the role of low-dose aspirin in patients who have had a first episode of unprovoked VTE and have a high risk of recurrence after anticoagulants are discontinued? Study design Multi-center Double blinded RCT Population Characteristics of study participants 46.0% female N = 822 54.0% male 822 patients (375 female, 447 male) Inclusion criteria: patients who had completed initial anticoagulant therapy after a first episode of unprovoked VTE Key exclusion criteria: first unprovoked episode of VTE > 2 years before enrollment; indication or contraindication for the use of aspirin, other antiplatelet therapy, or a nonsteroidal antiinflammatory drug; indication for continuing oral anticoagulation therapy; or other medical problems that would interfere with participation in the trial or limit life expectancy Interventions N=411 aspirin (100 mg PO once daily, for up to 4 years) N=411 placebo (matching placebo PO once daily, for up to 4 years) https://web.pathway.md/studies/rec7YXr21jVxwlsFZ 1/2 6/28/23, 12:45 AM ASPIRE Pathway Primary outcome Incidence of recurrent venous thromboembolism 6.5 % / y 6.5 4.9 % / y 4.8 3.3 % / y 1.6 % / y No significant difference 0.0 % / y Aspirin Placebo No significant difference in the incidence of recurrent VTE (4.8% / y vs. 6.5% / y; HR 0.74, 95% CI 0.52 to 1.05) Secondary outcomes Significant decrease in the incidence of major vascular events (5.2% / y vs. 8% / y; HR 0.66, 95% CI 0.48 to 0.92) Significant decrease in the incidence of VTE, myocardial infarction, stroke, major bleeding, or death (6% / y vs. 9% / y; HR 0.67, 95% CI 0.49 to 0.91) Safety outcomes No significant difference in major or clinically relevant nonmajor bleeding or serious adverse events. Conclusion In patients who had completed initial anticoagulant therapy after a first episode of unprovoked VTE, aspirin was not superior to placebo with respect to the incidence of recurrent VTE. Reference Brighton TA, Eikelboom JW, Mann K et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979-87. Open reference URL https://web.pathway.md/studies/rec7YXr21jVxwlsFZ 2/2
6/28/23, 12:45 AM ASPRE Pathway Feedback Search Clinical Topics Home Studies ASPRE ASPRE Disease Preeclampsia Trial question What is the effect of aspirin in women with singleton pregnancies who are at high risk for preterm preeclampsia? Study design Multi-center Double blinded RCT Population 1776 female patients Inclusion criteria: women with singleton pregnancies who are at high risk for preterm preeclampsia Key exclusion criteria: unconscious or severely ill status, learning difficulties or serious mental illness, major fetal abnormality identified at the time that scanning was performed at 11-13 weeks of gestation, von Willebrand's disease, peptic ulceration, hypersensitivity to aspirin, long-term use of nonsteroidal antiinflammatory medication Interventions N=798 aspirin (150 mg per day from 11-14 weeks gestation until 36 weeks of gestation) N=822 placebo (matching placebo from 11-14 weeks of gestation until 36 weeks of gestation) Primary outcome Preterm preeclampsia 4.3 4.3 % 3.2 % 2.1 % 1 6 https://web.pathway.md/studies/recWaqSbOc30GLikP 1/2 6/28/23, 12:45 AM ASPRE Pathway 1.6 Significant decrease 1.1 % NNT = 37 0.0 % Aspirin Placebo Significant decrease in preterm preeclampsia (1.6% vs. 4.3%; OR 0.38, 95% CI 0.2 to 0.74) Secondary outcomes No significant difference in stillbirth or death (1% vs. 1.7%; OR 0.59, 99% CI 0.19 to 1.85) Safety outcomes No significant difference in neonatal or other adverse events. Conclusion In women with singleton pregnancies who are at high risk for preterm preeclampsia, aspirin was superior to placebo with respect to preterm preeclampsia. Reference Rolnik DL, Wright D, Poon LC et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. Open reference URL https://web.pathway.md/studies/recWaqSbOc30GLikP 2/2
6/28/23, 12:46 AM ASPREE Pathway Feedback Search Clinical Topics Home Studies ASPREE ASPREE Disease Coronary artery disease Trial question What is the effect of daily aspirin in otherwise healthy older adults? Study design Multi-center Double blinded RCT Population Characteristics of study participants 56.0% female N = 19114 44.0% male 19114 patients (10782 female, 8332 male) Inclusion criteria: adult healthy patients ( 65 years of age) without CVD, dementia, or disability Key exclusion criteria: history of a diagnosed CVD event, AF, serious illness likely to cause death within the next 5 years, current or recurrent condition with a high risk of major bleeding, uncontrolled BP, anemia, current use of aspirin for secondary prevention, or current continuous use of other antiplatelet drug or anticoagulant Interventions N=9525 aspirin (100 mg daily) N=9589 placebo (matching tablet) Primary outcome https://web.pathway.md/studies/recFFF5KBU9DI9fAS 1/2 6/28/23, 12:46 AM ASPREE Pathway Incidence of death from all causes 12.7/1000 py 12.7 11.1 9.5/1000 py 6.3/1000 py 3.2/1000 py Borderline significant increase 0.0/1000 py Aspirin Placebo Borderline significant increase in the incidence of death from all causes (12.7 /1000 py vs. 11.1 /1000 py; HR 1.14, 95% CI 1.01 to 1.29) Secondary outcomes Borderline significant increase in cancer-related death (3.1% vs. 2.3%; HR 1.31, 95% CI 1.1 to 1.56) No significant difference in death from CVD, including ischemic stroke (1% vs. 1.2%; HR 0.82, 95% CI 0.62 to 1.08) No significant difference in death from major hemorrhage, including hemorrhagic stroke (0.3% vs. 0.3%; HR 1.13, 95% CI 0.66 to 1.94) Conclusion In adult healthy patients ( 65 years of age) without CVD, dementia, or disability, aspirin was inferior to placebo with respect to the incidence of death from all causes. Reference McNeil JJ, Nelson MR, Woods RL et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med. 2018 Oct 18;379(16):1519-1528. Open reference URL https://web.pathway.md/studies/recFFF5KBU9DI9fAS 2/2
6/28/23, 12:46 AM ASSIT Pathway Feedback Search Clinical Topics Home Studies ASSIT ASSIT Trial question Is extended-course antibiotic prophylaxis superior to short-course antibiotic prophylaxis in patients with lower limb amputation? Study design Single center Single blinded RCT Population Characteristics of study participants 28.0% female N = 152 72.0% male 152 patients (42 female, 110 male) Inclusion criteria: adults undergoing minor and major lower limb amputation Key exclusion criteria: known allergy to chlorhexidine/alcohol/iodophors; severe sepsis secondary to gas gangrene requiring multiple operations and admission to ICU; toe amputations Interventions N=76 extended-course antibiotic prophylaxis (5-day antibiotic course) N=76 short-course antibiotic prophylaxis (24-hour antibiotic course) Primary outcome Surgical-site infections at 30 days 39.5 39.5 % 29.6 % 19.8 % i ifi d https://web.pathway.md/studies/recqe4sLX2HH2Tqfj 1/2 6/28/23, 12:46 AM ASSIT Pathway Significant decrease 11.8 9.9 % NNT = 4 0.0 % Extended-course antibiotic prophylaxis Short-course antibiotic prophylaxis Significant decrease in surgical-site infections at 30 days (11.8% vs. 39.5%; ARD -27.7, 95% CI -44.14 to -11.26) Secondary outcomes Significant decrease in impaired wound healing (22.4% vs. 58%; RR 0.39, 95% CI 0.16 to 0.62) No significant difference in median duration of hospital stay (14 days vs. 15 days; AD -1 days, 95% CI -4.89 to 2.89) Significant decrease in the percentage of patients who had to return to the theater (6.6% vs. 21%; ARD -14.4, 95% CI -25.36 to -3.44) Safety outcomes No significant differences in death from any cause at 1 year, ICU admission, transfusion of blood products. Conclusion In adults undergoing minor and major lower limb amputation, extended-course antibiotic prophylaxis were superior to short-course antibiotic prophylaxis with respect to a surgical-site infections at 30 days. Reference Panayiotis Souroullas, Rachel Barnes, Daniel Carradice et al. Extended-course antibiotic prophylaxis in lower limb amputation: randomized clinical trial. Br J Surg. 2022 Apr 19;109(5):426- 432. Open reference URL https://web.pathway.md/studies/recqe4sLX2HH2Tqfj 2/2
6/28/23, 12:46 AM ASTRAL Pathway Feedback Search Clinical Topics Home Studies ASTRAL ASTRAL Disease Disease Hypertension Renal artery stenosis Trial question What is the role of percutaneous revascularization in patients with atherosclerotic renovascular disease? Study design Multi-center Open label RCT Population Characteristics of study participants 37.0% female N = 806 63.0% male 806 patients (299 female, 507 male) Inclusion criteria: patients with atherosclerotic renovascular disease Key exclusion criteria: requirement of surgical revascularization or high likelihood of requiring revascularization within 6 months, nonatheromatous CVD, or undergone previous revascularization for renal artery stenosis Interventions N=403 revascularization (with angioplasty either alone or with stenting plus medical therapy with statins, antiplatelet agents, and optimal blood-pressure control) N=403 medical therapy (statins, antiplatelet agents, and optimal blood-pressure control) https://web.pathway.md/studies/rec4BhsOgM7sgQC2B 1/2 6/28/23, 12:46 AM ASTRAL Pathway Primary outcome No significant difference in the incidence of decline in serum creatinine (-0.07 10 L/ mol/year vs. -0.13 10 L/ mol/year; MD 0.06, 95% CI 0 to 0.13) Secondary outcomes No significant difference in renal events (22% vs. 22%; HR 0.97, 95% CI 0.67 to 1.4) No significant difference in major cardiovascular events (49% vs. 51%; HR 0.94, 95% CI 0.75 to 1.19) No significant difference in death (60% vs. 57%; HR 0.9, 95% CI 0.69 to 1.18) Conclusion In patients with atherosclerotic renovascular disease, revascularization was superior to medical therapy with respect to the incidence of decline in serum creatinine. Reference ASTRAL Investigators, Wheatley K, Ives N et al. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009 Nov 12;361(20):1953-62. Open reference URL https://web.pathway.md/studies/rec4BhsOgM7sgQC2B 2/2
6/28/23, 12:46 AM ATACH II Pathway Feedback Search Clinical Topics Home Studies ATACH II ATACH II Disease Intracerebral hemorrhage Reference Qureshi AI, Palesch YY, Barsan WG et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43. Open reference URL https://web.pathway.md/studies/recU8b1wRiwfOeosM 1/1
6/28/23, 12:52 AM Atan Pathway Feedback Search Clinical Topics Home Studies Atan Atan Disease Acute kidney injury Trial question What is the role of continuous venovenous hemofiltration-high cutoff in critically ill patients with AKI? Study design Single center Double blinded RCT Population Characteristics of study participants 41.8% female N = 76 58.2% male 76 patients (31 female, 43 male) Inclusion criteria: patients in the ICU with AKI who were vasopressor-dependent Key exclusion criteria: age < 18 years, suspected death within 24 hours by the treating clinician, previous treatment with hemofiltration or another dialysis during the same hospital admission, maintenance dialysis prior to admission or pregnant or breastfeeding Interventions N=36 continuous venovenous hemofiltration-high cutoff (polyethersulfone high cutoff filter with nominal cutoff point of 100 kDa) N=38 continuous venovenous hemofiltration-standard (custom manufactured polyethersulfone standard hemofilter with nominal cutoff point of 30 kDa) https://web.pathway.md/studies/rec2hpgBgJPGdCyoP 1/2 6/28/23, 12:52 AM Atan Pathway Primary outcome Norepinephrine-free time over 7 days 56.0 hours 56 42.0 hours 32 28.0 hours 14.0 hours No significant difference 0.0 hours Continuous venovenous hemofiltration-high cutoff Continuous venovenous hemofiltration-standard No significant difference in norepinephrine-free time over 7 days (32 hours vs. 56 hours; AD -24 hours, 95% CI -95.32 to 47.32) Secondary outcomes No significant difference in death in the ICU (50% vs. 31.6%; OR 2.17, 95% CI 0.84 to 5.58) No significant difference in death in the hospital (55.6% vs. 34.2%; OR 2.4, 95% CI 0.94 to 6.15) No significant difference in dose of intravenous albumin given over the first 7 days (90 grams vs. 80 grams; AD 10 grams, 95% CI -6.94 to 26.94) Safety outcomes No significant differences in time to cessation of norepinephrine, time to cessation of hemofiltration, filter life, serum albumin levels, time to death. Conclusion In patients in the ICU with AKI who were vasopressor-dependent, continuous venovenous hemofiltration-high cutoff was not superior to continuous venovenous hemofiltration-standard with respect to a norepinephrine-free time over 7 days. Reference Rafidah Atan, Leah Peck, John Prowle et al. A Double-Blind Randomized Controlled Trial of High Cutoff Versus Standard Hemofiltration in Critically Ill Patients With Acute Kidney Injury. Crit Care Med. 2018 Oct;46(10):e988-e994. Open reference URL https://web.pathway.md/studies/rec2hpgBgJPGdCyoP 2/2
6/28/23, 12:46 AM ATESS Pathway Feedback Search Clinical Topics Home Studies ATESS ATESS Disease Sepsis and septic shock Trial question What is the effect of combination therapy of vitamin C and thiamine in patients with septic shock? Study design Multi-center Double blinded RCT Population Characteristics of study participants 60.0% female N = 111 40.0% male 111 patients (67 female, 44 male) Inclusion criteria: adult patients with septic shock Key exclusion criteria: transfer from another hospital with vasopressor administration or mechanical ventilator support, an underlying terminal-stage disease, taking at least 1 g/day of vitamin C or receiving intravenous thiamine prior to enrolment, cardiac arrest prior to enrolment, renal or ureteral stones Interventions N=53 vitamin C and thiamine (intravenous vitamin C 50 mg/kg, maximum single dose 3 g and thiamine 200 mg administration every 12 h for a total of 48 h) N=58 placebo (identical volume of 0.9% saline with the same protocol) https://web.pathway.md/studies/recQ6cdaagAQc4sgB 1/2 6/28/23, 12:46 AM ATESS Pathway Primary outcome Death at 28 days 20.8 % 20.8 15.6 % 15.5 10.4 % 5.2 % No significant difference 0.0 % Vitamin C and thiamine Placebo No significant difference in death at 28 days (20.8% vs. 15.5%; AD 5.2%, 95% CI -9.1 to 19.6) Secondary outcomes No significant difference in shock reversal (83% vs. 84.5%; ARD -1.5, 95% CI -15.2 to 12.3) Safety outcomes No significant differences in ventilator-free days, new-onset AKI, ICU-free days, reduction of procalcitonin. Significant difference in adverse events (0% vs. 3.5%). Conclusion In adult patients with septic shock, vitamin C and thiamine were not superior to placebo with respect to death at 28 days. Reference Sung Yeon Hwang, Seung Mok Ryoo, Jong Eun Park et al. Combination therapy of vitamin C and thiamine for septic shock: a multi-centre, double-blinded randomized, controlled study. Intensive Care Med. 2020 Nov;46(11):2015-2025. Open reference URL https://web.pathway.md/studies/recQ6cdaagAQc4sgB 2/2
6/28/23, 12:46 AM ATHOS-3 Pathway Feedback Search Clinical Topics Home Studies ATHOS 3 ATHOS 3 Trial question What is the effect of angiotensin II in patients with vasodilatory shock who do not respond to high- dose vasopressors? Study design Multi-center Double blinded RCT Population Characteristics of study participants 39.4% female N = 344 60.6% male 344 patients (126 female, 195 male) Inclusion criteria: patients with vasodilatory shock who were receiving > 0.2 g of norepinephrine per kg of body weight per minute or the equivalent dose of another vasopressor Key exclusion criteria: burns > 20% of total body-surface area, acute coronary syndrome, bronchospasm, liver failure, mesenteric ischemia, active bleeding, AAA, or an absolute neutrophil count of < 1,000/mm , or venoarterial ECMO or treatment with high-dose corticosteroids Interventions N=163 angiotensin II (synthetic human angiotensin II, LJPC-501 infusion) N=158 placebo (saline infusion) Primary outcome Percentage of patients achieving an elevation in blood pressure > 10 mmHg from baseline or an improvement to > 75 mmHg at 3 hours 69.9 % 69.9 52.4 % https://web.pathway.md/studies/recwPvUIbhuluZbVW 1/2 6/28/23, 12:46 AM ATHOS-3 Pathway 35.0 % Significant increase 23.4 17.5 % NNT = 2 0.0 % Angiotensin II Placebo Significant increase in the percentage of patients achieving an elevation in BP > 10 mmHg from baseline or an improvement to > 75 mmHg at 3 hours (69.9% vs. 23.4%; OR 7.95, 95% CI 4.76 to 13.3) Secondary outcomes Significant increase in mean cardiovascular SOFA score reduction at 48 hours (1.75 vs. 1.28; AD 1.37, 95% CI 0.33 to 2.41) Safety outcomes No significant differences in serious adverse events (60.7% vs. 67.1%) and death by day 28 (46% vs. 54%, p=0.12; HR 0.78, 95% CI 0.57-1.07). Conclusion In patients with vasodilatory shock who were receiving > 0.2 g of norepinephrine per kg of body weight per minute or the equivalent dose of another vasopressor, angiotensin II was superior to placebo with respect to the percentage of patients achieving an elevation in BP > 10 mmHg from baseline or an improvement to > 75 mmHg at 3 hours. Reference Khanna A, English SW, Wang XS et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. Open reference URL https://web.pathway.md/studies/recwPvUIbhuluZbVW 2/2
6/28/23, 12:47 AM ATLAS (cabotegravir and rilpivirine) Pathway Feedback Search Clinical Topics Home Studies ATLAS (cabotegravir and rilpivirine) ATLAS (cabotegravir and rilpivirine) Disease Human immunodeficiency virus i Trial question Is the combination of long-acting cabotegravir and rilpivirine non-inferior to standard oral antiretroviral therapy for the maintenance of human immunodeficiency virus type 1 infection suppression? Study design Multi-center Open label RCT Population Characteristics of study participants 33.0% female N = 618 67.0% male 618 patients (203 female, 413 male) Inclusion criteria: patients who had had plasma human immunodeficiency virus type 1 RNA levels < 50 copies/mL for at least 6 months while taking standard oral antiretroviral therapy Key exclusion criteria: evidence of active HBV infection, previous virologic failure, interruption of the current antiretroviral regimen within 6 months before screening, or any interruption exceeding 1 month in duration Interventions N=308 long-acting therapy (a 3 ml intramuscular injection of 600 mg cabotegravir and 900 mg rilpivirine, followed by a 2 ml injection of a dose of 400 mg and 600 mg every 4 weeks through https://web.pathway.md/studies/recNQqnNvVfn9ds2G 1/2 6/28/23, 12:47 AM ATLAS (cabotegravir and rilpivirine) Pathway week 52) N=308 oral therapy (continuation of the current antiretroviral regimen for 52 weeks) Primary outcome Human immunodeficiency virus type 1 RNA level 50 copies/ml at week 48 1.6 % 1.6 1.2 % 1 0.8 % Difference not exceeding nonferiority margin 0.4 % 0.0 % Long-acting therapy Oral therapy Difference not exceeding nonferiority margin in human immunodeficiency virus type 1 RNA level 50 copies/ml at week 48 (1.6% vs. 1%; AD 0.6%, 95% CI -1.2 to 2.5) Secondary outcomes No significant difference in human immunodeficiency virus type 1 RNA level < 50 copies/ml at week 48 (92.5% vs. 95.5%; ARD -3, 95% CI -6.7 to 0.7) Safety outcomes No significant difference in serious adverse events. Significant differences in at least one adverse event (95% vs. 71%), mild to moderate drug-related adverse events (29% vs. 3%). Conclusion In patients who had had plasma human immunodeficiency virus type 1 RNA levels < 50 copies/mL for at least 6 months while taking standard oral antiretroviral therapy, long-acting therapy was noninferior to oral therapy with respect to human immunodeficiency virus type 1 RNA level 50 copies/ml at week 48. Reference Susan Swindells, Jaime-Federico Andrade-Villanueva, Gary J Richmond et al. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression. N Engl J Med. 2020 Mar 19;382(12):1112-1123. Open reference URL https://web.pathway.md/studies/recNQqnNvVfn9ds2G 2/2
6/28/23, 12:47 AM ATLAS (tamoxifen) Pathway Feedback Search Clinical Topics Home Studies ATLAS (tamoxifen) ATLAS (tamoxifen) Trial question What are the long-term effects of continuing adjuvant tamoxifen to 10 years in women with estrogen receptor-positive breast cancer? Study design Multi-center Open label RCT Population 12894 female patients Inclusion criteria: women with estrogen receptor (ER)-positive early breast cancer who had completed 5 years of treatment with tamoxifen Key exclusion criteria: contraindications to continuation of tamoxifen, pregnancy, breastfeeding, retinopathy, need for coagulation therapy, endometrial hyperplasia, other serious toxicity attributed to tamoxifen, negligibly low risk of death from breast cancer, or presence of another life- threatening disease Interventions N=3428 extended tamoxifen use (continuation up to 10 years) N=3418 standard duration tamoxifen (stop at 5 years, with no placebo) Primary outcome Recurrent breast cancer 20.8 % 20.8 18 15.6 % 10.4 % Significant decrease 5.2 % NNT = 36 0.0 % Extended tamoxifen use Standard duration tamoxifen Significant decrease in recurrent breast cancer (18% vs. 20.8%; RR 0.84, 95% CI 0.76 to 0.94) Secondary outcomes https://web.pathway.md/studies/reclazgWls1ldPjSd 1/2 6/28/23, 12:47 AM ATLAS (tamoxifen) Pathway Significant decrease in breast cancer death (12.2% vs. 15%; RR 0.71, 95% CI 0.58 to 0.88) Significant decrease in death from any cause (18.6% vs. 21.1%; RR 0.87, 95% CI 0.78 to 0.97) Significant decrease in cumulative risk of breast cancer recurrence (21.4% vs. 25.1%; RR 0.75, 95% CI 0.62 to 0.9) Safety outcomes No significant differences in primary liver cancer, colorectal cancer, stroke. Significant differences in hospitalization due to pulmonary embolus (0.6% vs. 0.3%), ischemic heart disease (2.0% vs. 1.0%), and endometrial cancer (1.8% vs. 1.0%), cumulative risk of endometrial cancer during year 5-14 (3.1% vs. 1.6%). Conclusion In women with estrogen receptor (ER)-positive early breast cancer who had completed 5 years of treatment with tamoxifen, extended tamoxifen use was superior to standard duration tamoxifen with respect to recurrent breast cancer. Reference Davies C, Pan H, Godwin J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. Open reference URL https://web.pathway.md/studies/reclazgWls1ldPjSd 2/2
6/28/23, 12:47 AM ATLAS ACS-2, TIMI 51 Pathway Feedback Search Clinical Topics Home Studies ATLAS ACS 2, TIMI 51 ATLAS ACS 2, TIMI 51 Disease Disease Non-ST-elevation myocardial inf ST-elevation myocardial infarction Reference Mega JL, Braunwald E, Wiviott SD et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Jan 5;366(1):9-19. Open reference URL https://web.pathway.md/studies/recnKsywVFJqF2KDi 1/1
6/28/23, 12:47 AM ATLAS-2M (152-week results) Pathway Feedback Search Clinical Topics Home Studies ATLAS 2M 152-week results) ATLAS 2M 152-week results) Disease Human immunodeficiency virus i Trial question Is administration of cabotegravir plus rilpivirine every 8 weeks noninferior to administration every 4 weeks in adults with human immunodeficiency virus-1 infection? Study design Multi-center Open label RCT Population Characteristics of study participants 27.0% female N = 1045 73.0% male 1045 patients (280 female, 765 male) Inclusion criteria: adults living with human immunodeficiency virus-1 infection Key exclusion criteria: pregnancy; moderate to severe hepatic impairment; preexisting physical or mental condition; high risk for seizures Interventions N=522 every 8 weeks dosing (cabotegravir 600 mg plus rilpivirine 900 mg administered IM every 8 weeks) N=523 every 4 weeks dosing (cabotegravir 400 mg plus rilpivirine 600 mg administered IM every 4 weeks) https://web.pathway.md/studies/recSY1Zb52a8MNkU2 1/2 6/28/23, 12:47 AM ATLAS-2M (152-week results) Pathway Primary outcome HIV-1 RNA 50 copies/mL at week 152 2.7 % 2.7 2.0 % 1.4 % 1 Difference not exceeding nonferiority margin 0.7 % 0.0 % Every 8 weeks dosing Every 4 weeks dosing Difference not exceeding nonferiority margin in HIV-1 RNA 50 copies/mL at week 152 (2.7% vs. 1%; AD 1.7%, 95% CI 0.1 to 3.3) Secondary outcomes No significant difference in HIV-1 RNA < 50 copies/mL at week 152 (87.4% vs. 85.9%; AD 1.5%, 95% CI -2.6 to 5.6) No significant difference in the rate of test for homogeneity by strata for HIV-1 RNA < 50 copies/mL at > 24 weeks (91.3% vs. 89.1%; AD -2.2%, 95% CI -5.6 to 10) Safety outcomes No significant difference in adverse events. Conclusion In adults living with human immunodeficiency virus-1 infection, every 8 weeks dosing was noninferior to every 4 weeks dosing with respect to a HIV-1 RNA 50 copies/mL at week 152. Reference Edgar T Overton, Gary Richmond, Giuliano Rizzardini et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection: 152-week results from ATLAS-2M, a randomized, open-label, Phase 3b, noninferiority study. Clin Infect Dis. 2023 Jan 20;ciad020. Open reference URL https://web.pathway.md/studies/recSY1Zb52a8MNkU2 2/2
6/28/23, 12:47 AM ATLAS-2M (48-week results) Pathway Feedback Search Clinical Topics Home Studies ATLAS 2M 48-week results) ATLAS 2M 48-week results) Disease Human immunodeficiency virus i Trial question Is administration of cabotegravir plus rilpivirin every 8 weeks noninferior to administration every 4 weeks in adults with human immunodeficiency virus-1 infection? Study design Multi-center Open label RCT Population Characteristics of study participants 27.0% female N = 1045 73.0% male 1045 patients (280 female, 765 male) Inclusion criteria: adults living with human immunodeficiency virus-1 infection Key exclusion criteria: pregnancy, moderate to severe hepatic impairment, preexisting physical or mental condition, high risk for seizures Interventions N=522 every 8 weeks dosing (cabotegravir 600 mg plus rilpivirine 900 mg administered IM every 8 weeks) N=523 every 4 weeks dosing (cabotegravir 400 mg plus rilpivirine 600 mg administered IM every 4 weeks) https://web.pathway.md/studies/recv1VWngvkS2mxQ5 1/2 6/28/23, 12:47 AM ATLAS-2M (48-week results) Pathway Primary outcome HIV-1 RNA 50 copies/mL at week 48 2.0 % 2 1.5 % 1.0 % 1 Difference not exceeding nonferiority margin 0.5 % 0.0 % Every 8 weeks dosing Every 4 weeks dosing Difference not exceeding nonferiority margin in HIV-1 RNA 50 copies/mL at week 48 (2% vs. 1%; AD 0.8%, 95% CI -0.6 to 2.2) Secondary outcomes No significant difference in HIV-1 RNA < 50 copies/mL at week 48 (94% vs. 93%; AD 0.8%, 95% CI -2.1 to 3.7) No significant difference in the rate of test for homogeneity by stratum for plasma HIV-1 RNA 50 copies/mL at > 24 weeks (AD 0.8%, 95% CI -2.2 to 4.4) No significant difference in the rate of test for homogeneity by stratum for plasma HIV-1 RNA < 50 copies/mL at > 24 weeks (95% vs. 97%; ARD -1.6, 95% CI -7.4 to 3.7) Safety outcomes No significant difference in adverse events. Conclusion In adults living with human immunodeficiency virus-1 infection, every 8 weeks dosing was noninferior to every 4 weeks dosing with respect to a HIV-1 RNA 50 copies/mL at week 48. Reference Edgar T Overton, Gary Richmond, Giuliano Rizzardini et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2021 Dec 19;396(10267):1994- 2005. Open reference URL https://web.pathway.md/studies/recv1VWngvkS2mxQ5 2/2
6/28/23, 12:48 AM ATN Pathway Feedback Search Clinical Topics Home Studies ATN ATN Disease Acute kidney injury Trial question What is the effect of intensive renal support in critically ill patients with AKI? Study design Multi-center Open label RCT Population Characteristics of study participants 29.0% female N = 1124 71.0% male 1124 patients (330 female, 793 male) Inclusion criteria: critically ill patients with AKI and failure of at least one nonrenal organ or sepsis Key exclusion criteria: > 1 hemodialysis treatment or > 24 hours of continuous RRT, prior kidney transplant, pregnancy, moribund state, acute renal failure due to an etiology other than acute tubular necrosis, or weight > 128.5 kg Interventions N=563 intensive RRT (intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 mL/kg of body weight per hour) N=561 less-intensive RRT (the corresponding treatments provided thrice weekly and at 20 mL/kg/hour) https://web.pathway.md/studies/recQ5EoBLfn67RwyZ 1/2 6/28/23, 12:48 AM ATN Pathway Primary outcome Death at 60 days 53.6 % 53.6 51.5 40.2 % 26.8 % 13.4 % No significant difference 0.0 % Intensive renal replacement therapy Less-intensive renal replacement therapy No significant difference in death at 60 days (53.6% vs. 51.5%; OR 1.09, 95% CI 0.86 to 1.4) Secondary outcomes Borderline significant decrease in the rate of recovery of kidney function by day 28 (24.3% vs. 27.4%; OR 0.03, 95% CI 0.02 to 0.07) No significant difference in in-hospital death (51.2% vs. 48%; OR 1.15, 95% CI 0.9 to 1.47) Safety outcomes No significant differences in serious adverse event (51.0% vs. 49.9%, p=0.72) and hypotension requiring treatment discontinuation (9.8% vs. 8.7%, p=0.55). Significant differences in hypokalemia (7.5% vs. 4.5%, p = 0.03) and hypophosphatemia (17.6% vs. 10.9%, p = 0.001). Conclusion In critically ill patients with AKI and failure of at least one nonrenal organ or sepsis, intensive RRT was not superior to less-intensive RRT with respect to death at 60 days. Reference VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3;359(1):7-20. Open reference URL https://web.pathway.md/studies/recQ5EoBLfn67RwyZ 2/2
6/28/23, 12:48 AM ATTKPATRASCOVID19 Pathway Feedback Search Clinical Topics Home Studies ATTKPATRASCOVID19 ATTKPATRASCOVID19 Disease COVID 19 infection Trial question Is baricitinib noninferior to tocilizumab in patients with severe COVID-19 infection? Study design Single center Open label RCT Population Characteristics of study participants 41.0% female N = 251 59.0% male 251 patients (103 female, 148 male) Inclusion criteria: patients with COVID-19 and the ratio of partial pressure of oxygen to FiO2 < 200 Key exclusion criteria: age < 18 years; pregnancy; eGFR < 30 mL/min/1.73 m ; mechanical ventilation prior to randomization Interventions N=125 baricitinib (at a dose of 4 mg/day for up to 14 days or until discharge) N=125 tocilizumab (a single infusion of 8 mg/kg plus standard care) Primary outcome Rate of mechanical ventilation or death by day 28 44.4 44.4 % https://web.pathway.md/studies/reclc4HuFbuI1KWKa 1/2 6/28/23, 12:48 AM 44.4 % ATTKPATRASCOVID19 Pathway 39.2 33.3 % 22.2 % Difference not exceeding nonferiority margin 11.1 % 0.0 % Baricitinib Tocilizumab Difference not exceeding nonferiority margin in the rate of mechanical ventilation or death by day 28 (39.2% vs. 44.4%; HR 0.83, 95% CI 0.56 to 1.21) Secondary outcomes Significant increase in the rate of the percentage of patients who were discharged alive after 28 days (58.4% vs. 52.4%; HR 1.17, 95% CI 0.84 to 1.63) Significant decrease in the rate of death within 28 days (32% vs. 39.7%; HR 0.73, 95% CI 0.49 to 1.09) Safety outcomes No significant difference in 1 adverse event. Significant difference in increased liver transaminases (2.4% vs. 7.9%). Conclusion In patients with COVID-19 and the ratio of partial pressure of oxygen to FiO2 < 200, baricitinib was noninferior to tocilizumab with respect to the rate of mechanical ventilation or death by day 28. Reference Theodoros Karampitsakos, Ourania Papaioannou, Panagiota Tsiri et al. Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial. Clin Microbiol Infect. 2022 Oct 20;S1198-743X(22)00529-8. Open reference URL https://web.pathway.md/studies/reclc4HuFbuI1KWKa 2/2
6/28/23, 12:48 AM ATTR-ACT Pathway Feedback Search Clinical Topics Home Studies ATTR ACT ATTR ACT Disease Disease Disease Cardiac amyloidosis Dilated cardiomyopathy Heart failu Reference Maurer MS, Schwartz JH, Gundapaneni B et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. Open reference URL https://web.pathway.md/studies/recDUO1GEx2Di2R2n 1/1
6/28/23, 12:48 AM ATTRACT Pathway Feedback Search Clinical Topics Home Studies ATTRACT ATTRACT Disease Disease Deep vein thrombosis Pulmonary embolism Trial question What is the role of pharmacomechanical catheter-directed thrombolysis in reducing the risk of post- thrombotic syndrome in patients with proximal deep vein thrombosis despite treatment with anticoagulant therapy? Study design Multi-center Open label RCT Population Characteristics of study participants 38.0% female N = 692 62.0% male 692 patients (265 female, 426 male) Inclusion criteria: patients with proximal deep vein thrombosis despite treatment with anticoagulant therapy Key exclusion criteria: < 16 or > 75 years of age, pregnant, symptoms for > 14 days, high risk bleeding, active cancer, established post-thrombotic syndrome, or ipsilateral deep vein thrombosis in the previous 2 years Interventions N=337 pharmacomechanical-thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tPA and thrombus aspiration or maceration, with or without stenting plus https://web.pathway.md/studies/recShUKhWY9BChDqS 1/2 6/28/23, 12:48 AM ATTRACT Pathway anticoagulation) N=355 medical therapy (anticoagulation alone) Primary outcome Rate of post-thrombotic syndrome between 6 and 24 months 48.0 % 48 47 36.0 % 24.0 % 12.0 % No significant difference 0.0 % Pharmacomechanical-thrombolysis Medical therapy No significant difference in the rate of post-thrombotic syndrome between 6 and 24 months (47% vs. 48%; RR 0.96, 96% CI 0.82 to 1.11) Secondary outcomes Significant decrease in moderate-to-severe post-thrombotic syndrome (18% vs. 24%; RR 0.73, 95% CI 0.54 to 0.98) Safety outcomes No significant difference in death and major bleeding over 24 months. Significant differences in major bleeding during the first 10 days (1.7% vs. 0.3%; p = 0.049; RR 6.18, 95% CI 0.78-49.2) and recurrent VTE within 24 months (12% vs. 8%, p = 0.09). Conclusion In patients with proximal deep vein thrombosis despite treatment with anticoagulant therapy, pharmacomechanical-thrombolysis were not superior to medical therapy with respect to the rate of post-thrombotic syndrome between 6 and 24 months. Reference Vedantham S, Goldhaber SZ, Julian JA et al. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-2252. Open reference URL https://web.pathway.md/studies/recShUKhWY9BChDqS 2/2
6/28/23, 12:48 AM AUGUSTUS (anticoagulation regimen) Pathway Feedback Search Clinical Topics Home Studies AUGUSTUS (anticoagulation regimen) AUGUSTUS (anticoagulation regimen) Disease Disease Disease Atrial fibrillation Non-ST-elevation myocardial inf ST-elevat Trial question Is apixaban superior to vitamin K antagonist in patients with AF and acute coronary syndrome or PCI? Study design Multi-center Open label RCT Population Characteristics of study participants 29.0% female N = 4614 71.0% male 4614 patients (1337 female, 3277 male) Inclusion criteria: patients with AF who had acute coronary syndrome or had undergone PCI Key exclusion criteria: anticoagulation therapy for other conditions; severe renal insufficiency; intracranial hemorrhage; CABG surgery; coagulopathy or ongoing bleeding Interventions N=2306 apixaban (at a dose of 2.5-5 mg PO BID) N=2308 vitamin K antagonist (tablets once daily adjusted to reach a target INR of 2.0-3.0) Primary outcome Major or clinically relevant nonmajor bleeding https://web.pathway.md/studies/rec2rEL8qcehO4W88 1/2 6/28/23, 12:48 AM AUGUSTUS (anticoagulation regimen) Pathway 14.7 % 14.7 11.0 % 10.5 7.3 % Significant decrease 3.7 % NNT = 24 0.0 % Apixaban Vitamin K antagonist Significant decrease in major or clinically relevant nonmajor bleeding (10.5% vs. 14.7%; HR 0.69, 95% CI 0.58 to 0.81) Secondary outcomes Significant decrease in death or hospitalization (23.5% vs. 27.4%; HR 0.83, 95% CI 0.74 to 0.93) No significant difference in death or ischemic event (6.7% vs. 7.1%; HR 0.93, 95% CI 0.75 to 1.16) No significant difference in death (3.3% vs. 3.2%; HR 1.03, 95% CI 0.75 to 1.42) Safety outcomes No significant difference in intracranial hemorrhage. Significant differences in major bleeding (3.0% vs. 4.6%), clinically relevant nonmajor bleeding (7.9% vs. 10.9%). Conclusion In patients with AF who had acute coronary syndrome or had undergone PCI, apixaban was superior to vitamin K antagonist with respect to major or clinically relevant nonmajor bleeding. Reference Renato D Lopes, Gretchen Heizer, Ronald Aronson et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med. 2019 Apr 18;380(16):1509-1524. Open reference URL https://web.pathway.md/studies/rec2rEL8qcehO4W88 2/2
6/28/23, 12:48 AM AUGUSTUS (antiplatelet regimen) Pathway Feedback Search Clinical Topics Home Studies AUGUSTUS (antiplatelet regimen) AUGUSTUS (antiplatelet regimen) Disease Disease Disease Atrial fibrillation Non-ST-elevation myocardial inf ST-elevat Trial question What is the role of aspirin in patients with AF and acute coronary syndrome or PCI? Study design Multi-center Double blinded RCT Population Characteristics of study participants 29.0% female N = 4614 71.0% male 4614 patients (1337 female, 3277 male) Inclusion criteria: patients with AF who had acute coronary syndrome or had undergone PCI Key exclusion criteria: anticoagulation therapy for other conditions; severe renal insufficiency; intracranial hemorrhage; CABG surgery; coagulopathy or ongoing bleeding Interventions N=2307 aspirin (81 mg acetylsalicylic acid tablet PO once daily) N=2307 placebo (matching placebo once daily) Primary outcome Major or clinically relevant nonmajor bleeding 16.1 % 16.1 https://web.pathway.md/studies/recUsGNqQDoria1Hc 1/2 6/28/23, 12:48 AM AUGUSTUS (antiplatelet regimen) Pathway 6 12.1 % 9 8.1 % Significant increase 4.0 % NNH = 14 0.0 % Aspirin Placebo Significant increase in major or clinically relevant nonmajor bleeding (16.1% vs. 9%; HR 1.89, 95% CI 1.59 to 2.24) Secondary outcomes No significant difference in death or hospitalization (26.2% vs. 24.7%; HR 1.08, 95% CI 0.96 to 1.21) No significant difference in death or ischemic event (6.5% vs. 7.3%; HR 0.89, 95% CI 0.71 to 1.11) No significant difference in death (3.1% vs. 3.4%; HR 0.91, 95% CI 0.66 to 1.26) Safety outcomes No significant differences in intracranial hemorrhage, severe bleeding. Significant differences in major bleeding (4.7% vs. 2.9%), clinically relevant nonmajor bleeding (12.1% vs. 6.5%). Conclusion In patients with AF who had acute coronary syndrome or had undergone PCI, aspirin was inferior to placebo with respect to major or clinically relevant nonmajor bleeding. Reference Renato D Lopes, Gretchen Heizer, Ronald Aronson et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med. 2019 Apr 18;380(16):1509-1524. Open reference URL https://web.pathway.md/studies/recUsGNqQDoria1Hc 2/2
6/28/23, 12:49 AM AURORA Pathway Feedback Search Clinical Topics Home Studies AURORA AURORA Disease Disease Disease Acute ischemic stroke Chronic kidney disease Dyslipidem Trial question What is the effect of rosuvastatin on the incidence of cardiovascular events in patients undergoing hemodialysis? Study design Multi-center Double blinded RCT Population Characteristics of study participants 38.0% female N = 2776 62.0% male 2776 patients (1050 female, 1723 male) Inclusion criteria: patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis Key exclusion criteria: statin therapy within the previous 6 months, expected kidney transplantation within 1 year, and serious hematologic, neoplastic, gastrointestinal, infectious, or metabolic disease (excluding diabetes) predicted to limit life expectancy < 1 year, history of a malignant condition, active liver disease, or uncontrolled hypothyroidism Interventions N=1391 rosuvastatin (10 mg daily) N=1385 placebo (matching placebo daily) https://web.pathway.md/studies/recq9Dg4sgQeTUu0y 1/2 6/28/23, 12:49 AM AURORA Pathway Primary outcome Death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (events per 100 patient-years) 9.5 9.5 9.2 7.1 4.8 2.4 No significant difference 0.0 Rosuvastatin Placebo No significant difference in death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (events per 100 patient-years) (9.2 vs. 9.5; HR 0.96, 96% CI 0.84 to 1.11) Secondary outcomes No significant difference in the incidence of death from any cause (13.5 /100 py vs. 14 /100 py; HR 0.96, 96% CI 0.86 to 1.07) No significant difference in the incidence of cardiovascular death (7.2 person-years vs. 7.3 person-years; HR 1, 95% CI 0.85 to 1.16) No significant difference in death due to noncardiovascular causes (events per 100 patient-years) (5.5 vs. 6; HR 0.92, 95% CI 0.77 to 1.09) Safety outcomes Significant differences in mean change in LDL cholesterol levels at 3 months (42.9% vs. 1.9%, p < 0.001). Conclusion In patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis, rosuvastatin was not superior to placebo with respect to death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (events per 100 patient-years). Reference Fellstrom BC, Jardine AG, Schmieder RE et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009 Apr 2;360(14):1395-407. Open reference URL https://web.pathway.md/studies/recq9Dg4sgQeTUu0y 2/2
6/28/23, 12:49 AM AUSTRI Pathway Feedback Search Clinical Topics Home Studies AUSTRI AUSTRI Disease Disease Asthma Severe asthma phenotypes Trial question Is salmeterol plus fluticasone noninferior to fluticasone alone in patients with persistent asthma and a history of severe asthma exacerbations? Study design Multi-center Double blinded RCT Population Characteristics of study participants 66.0% female N = 11679 34.0% male 11679 patients (7749 female, 3930 male) Inclusion criteria: patients with persistent asthma who had a history of a severe asthma exacerbation in the year before randomization, but not during the previous month Key exclusion criteria: history of life-threatening, cigarette smoking for > 10 pack-years or unstable asthma Interventions N=5834 fluticasone-salmeterol inhaler therapy (at a dose of 100 g and 50 g, 250 g and 50 g, or 500 g and 50 g of fluticasone and salmeterol, respectively, administered BID) N=5845 fluticasone-only inhaler therapy (at a dose of 100 g, 250 g, or 500 g, administered BID) https://web.pathway.md/studies/recf6VZ4PKqxQFopX 1/2 6/28/23, 12:49 AM AUSTRI Pathway Primary outcome Serious asthma-related events 38.0 38 36 28.5 19.0 Difference not exceeding nonferiority margin 9.5 0.0 Fluticasone-salmeterol inhaler therapy Fluticasone-only inhaler therapy Difference not exceeding nonferiority margin in serious asthma-related events (36 vs. 38; HR 1.03, 95% CI 0.64 to 1.66) Secondary outcomes Significant decrease in severe asthma exacerbation, at least one (8% vs. 10%; HR 0.79, 95% CI 0.7 to 0.89) Safety outcomes No significant difference in asthma-related hospitalizations (34 vs. 33) and there were no reported asthma-related death in either group. Conclusion In patients with persistent asthma who had a history of a severe asthma exacerbation in the year before randomization, but not during the previous month, fluticasone-salmeterol inhaler therapy was noninferior to fluticasone-only inhaler therapy with respect to serious asthma-related events. Reference Stempel DA, Raphiou IH, Kral KM et al. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. N Engl J Med. 2016 May 12;374(19):1822-30. Open reference URL https://web.pathway.md/studies/recf6VZ4PKqxQFopX 2/2
6/28/23, 12:49 AM AVB-TIPS Pathway Feedback Search Clinical Topics Home Studies AVB TIPS AVB TIPS Disease Disease Disease Hepatic encephalopathy Liver cirrhosis Portal hyp Trial question What is the role of early placement of TIPSs in patients with advanced cirrhosis and acute variceal bleeding? Study design Single center Open label RCT Population Characteristics of study participants 33.0% female N = 129 67.0% male 129 patients (42 female, 87 male) Inclusion criteria: patients with advanced cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy Key exclusion criteria: uncontrolled bleeding before randomization; spontaneous recurrent hepatic encephalopathy; HCC or other extrahepatic malignancy; previous treatments with a surgical shunt Interventions N=84 early TIPS (done within 72 hours after initial endoscopy) N=45 standard care (vasoactive drugs continued to day 5, followed by propranolol plus endoscopic band ligation, with TIPS as rescue therapy as needed) https://web.pathway.md/studies/recJt1NhXKkkbuSSC 1/2 6/28/23, 12:49 AM AVB-TIPS Pathway Primary outcome Death or liver transplantation 36.0 % 36 27.0 % 20 18.0 % Significant decrease 9.0 % NNT = 6 0.0 % Early transjugular intrahepatic portosystemic shunt Standard care Significant decrease in death or liver transplantation (20% vs. 36%; HR 0.5, 95% CI 0.25 to 0.98) Secondary outcomes Significant decrease in failure to control bleeding or rebleeding (13% vs. 38%; HR 0.26, 95% CI 0.12 to 0.55) Significant decrease in new or worsening ascites (17% vs. 44%; HR 0.28, 95% CI 0.14 to 0.55) No significant difference in overt hepatic encephalopathy (35% vs. 36%; HR 0.89, 95% CI 0.48 to 1.64) Safety outcomes No significant differences in hepatic hydrothorax, SBP, hepatorenal syndrome, HCC, other serious adverse events or non-serious adverse events. Conclusion In patients with advanced cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy, early TIPS was superior to standard care with respect to death or liver transplantation. Reference Yong Lv, Zhiping Yang, Lei Liu et al. Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Aug;4(8):587-598. Open reference URL https://web.pathway.md/studies/recJt1NhXKkkbuSSC 2/2
6/28/23, 12:49 AM AVERROES Pathway Feedback Search Clinical Topics Home Studies AVERROES AVERROES Disease Disease Disease Acute ischemic stroke Atrial fibrillation Transient Trial question What is the role of apixaban in patients with AF who are at an increased risk for stroke for whom vitamin K antagonist therapy is unsuitable? Study design Multi-center Double blinded RCT Population Characteristics of study participants 41.0% female N = 5599 59.0% male 5599 patients (2322 female, 3277 male) Inclusion criteria: patients with AF who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable Key exclusion criteria: valvular disease requiring surgery, a serious bleeding event in the previous 6 months or a high risk of bleeding, current alcohol or drug abuse or psychosocial issues, life expectancy < 1 year, or severe renal insufficiency Interventions N=2808 apixaban (5 mg PO BID) N=2791 aspirin (81-324 mg PO once daily) https://web.pathway.md/studies/recwpHaKUTiCV5d8k 1/2 6/28/23, 12:49 AM AVERROES Pathway Primary outcome Incidence of stroke or systemic embolism 3.7 % / y 3.7 2.8 % / y 1.9 % / y 1.6 0.9 % / y Significant decrease 0.0 % / y Apixaban Aspirin Significant decrease in the incidence of stroke or systemic embolism (1.6% / y vs. 3.7% / y; HR 0.45, 95% CI 0.32 to 0.62) Secondary outcomes No significant difference in death (3.5% vs. 4.4%; HR 0.79, 95% CI 0.62 to 1.02) Significant decrease in hospitalization for cardiovascular causes (12.6% vs. 15.9%; HR 0.79, 95% CI 0.69 to 0.91) Safety outcomes No significant differences in major bleeding (1.4% vs. 1.2%, p=0.57; HR 1.13, 95% CI 0.74-1.75). Significant differences in serious adverse event (22% vs. 27%, p < 0.001). Conclusion In patients with AF who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable, apixaban was superior to aspirin with respect to the incidence of stroke or systemic embolism. Reference Connolly SJ, Eikelboom J, Joyner C et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3;364(9):806-17. Open reference URL https://web.pathway.md/studies/recwpHaKUTiCV5d8k 2/2
6/28/23, 12:50 AM AVERT (subgroup analysis) Pathway Feedback Search Clinical Topics Home Studies AVERT (subgroup analysis) AVERT (subgroup analysis) Disease Disease Cancer-associated thrombosis Catheter-related thrombosis Trial question What is the effect of apixaban in patients with cancer and a central venous catheter? Study design Multi-center Double blinded RCT Population 217 patients Inclusion criteria: patients with cancer-initiating chemotherapy who were at intermediate-to-high risk of VTE Key exclusion criteria: lesions or conditions leading to increased risk of clinically significant bleeding; liver insufficiency; planned stem cell transplant; life expectancy < 6 months Interventions N=126 apixaban (a dose of 2.5 mg BID for 6 months) N=91 placebo (matching placebo for 6 months) Primary outcome Venous thromboembolism at 180 days 18.7 18.7 % 14.0 % 9.3 % Significant decrease 4.8 4 7 % https://web.pathway.md/studies/recpunmuJEDb44n2Q 1/2 6/28/23, 12:50 AM AVERT (subgroup analysis) Pathway 4.7 % NNT = 7 0.0 % Apixaban Placebo Significant decrease in VTE at 180 days (4.8% vs. 18.7%; HR 0.26, 95% CI 0.14 to 0.47) Secondary outcomes Significant decrease in proximal deep vein thrombosis at 180 days (3.2% vs. 12.4%; HR 0.26, 95% CI 0.12 to 0.55) Significant decrease in death at 180 days (0.8% vs. 2.2%; HR 0.35, 95% CI 0.24 to 0.49) Safety outcomes No significant differences in major bleeding, clinically relevant non-major bleeding. Conclusion In patients with cancer-initiating chemotherapy who were at intermediate-to-high risk of VTE, apixaban was superior to placebo with respect to VTE at 180 days. Reference Willem Brandt, Cameron Brown, Tzu-Fei Wang et al. Efficacy and safety of apixaban for primary prevention of thromboembolism in patients with cancer and a central venous catheter: A subgroup analysis of the AVERT Trial. Thromb Res. 2022 May 29;216:8-10. Open reference URL https://web.pathway.md/studies/recpunmuJEDb44n2Q 2/2
6/28/23, 12:50 AM AVERT Shock Pathway Feedback Search Clinical Topics Home Studies AVERT Shock AVERT Shock Disease Traumatic hemorrhage Trial question What is the effect of low-dose supplementation of arginine vasopressin in patients with trauma and hemorrhagic shock? Study design Single center Double blinded RCT Population Characteristics of study participants 7.0% female N = 100 93.0% male 100 patients (7 female, 93 male) Inclusion criteria: adult trauma patients, aged 18-65 years, who received at least 6 U of any blood product within 12 hours of injury Key exclusion criteria: prehospital CPR, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, or arginine vasopressin administration before enrollment Interventions N=49 arginine vasopressin supplementation (4 U of bolus followed by 0.04 U/min infusion for 48 hours to maintain a mean arterial BP of at least 65 mmHg) https://web.pathway.md/studies/rect0bm3vBYDnT3eV 1/2 6/28/23, 12:50 AM AVERT Shock Pathway N=51 placebo (an equivalent volume of saline infusion for 48 hours to maintain a mean arterial BP of at least 65 mmHg) Primary outcome Total volume of blood product transfused at 48 hours 2.9 L 2.9 2.2 L 1.4 L 1.4 0.7 L Significant decrease 0.0 L Arginine vasopressin supplementation Placebo Significant decrease in total volume of blood product transfused at 48 hours (1.4 L vs. 2.9 L; AD -1.1 L, 95% CI -2.04 to 0) Secondary outcomes No significant difference in total vasopressor equivalents at 48 hours (0.4 g vs. 1.4 g; AD -0.23 g, 95% CI -1.37 to 0.53) No significant difference in crystalloid equivalents at 48 hours (9.9 L vs. 11 L; AD -1.07 L, 95% CI -3.04 to 0.62) No significant difference in death (12% vs. 12%; RR 1.04, 95% CI 0.36 to 3.01) Safety outcomes No significant difference in adverse events. Significant difference in deep vein thrombosis (11% vs. 34%). Conclusion In adult trauma patients, aged 18-65 years, who received at least 6 U of any blood product within 12 hours of injury, arginine vasopressin supplementation was superior to placebo with respect to total volume of blood product transfused at 48 hours. Reference Carrie A Sims, Daniel Holena, Patrick Kim et al. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial. JAMA Surg. 2019 Nov 1;154(11):994-1003. Open reference URL https://web.pathway.md/studies/rect0bm3vBYDnT3eV 2/2
6/28/23, 12:49 AM AVERT Pathway Feedback Search Clinical Topics Home Studies AVERT AVERT Disease Disease Deep vein thrombosis Pulmonary embolism Trial question What is the effect of thromboprophylaxis with apixaban in intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy? Study design Multi-center Double blinded RCT Population Characteristics of study participants 57.0% female N = 563 43.0% male 563 patients (323 female, 240 male) Inclusion criteria: ambulatory patients with cancer who were at intermediate-to-high risk for VTE and were initiating chemotherapy Key exclusion criteria: increased risk for clinically significant bleeding, hepatic disease associated with coagulopathy, basal cell carcinoma, SCC, acute leukemia, myeloproliferative neoplasm, stem cell transplantation Interventions N=288 apixaban (2.5 mg BID for 180 days) N=275 placebo (identical tablets BID for 180 days) https://web.pathway.md/studies/recmFevGXOdL9VuoM 1/2 6/28/23, 12:49 AM AVERT Pathway Primary outcome Rate of venous thromboembolism within 180 days 10.2 % 10.2 7.6 % 5.1 % 4.2 Significant decrease 2.5 % NNT = 17 0.0 % Apixaban Placebo Significant decrease in the rate of VTE within 180 days (4.2% vs. 10.2%; HR 0.41, 95% CI 0.26 to 0.65) Secondary outcomes Significant increase in major bleeding in modified intention-to-treat analysis (3.5% vs. 1.8%; HR 2, 95% CI 1.01 to 3.95) Safety outcomes No significant differences in major bleeding during treatment period (2.1% vs. 1.1%; HR 1.89, 95% CI 0.39-9.24). Conclusion In ambulatory patients with cancer who were at intermediate-to-high risk for VTE and were initiating chemotherapy, apixaban was superior to placebo with respect to the rate of VTE within 180 days. Reference Carrier M, Abou-Nassar K, Mallick R et al. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. Open reference URL https://web.pathway.md/studies/recmFevGXOdL9VuoM 2/2
6/28/23, 12:50 AM AVOID Pathway Feedback Search Clinical Topics Home Studies AVOID AVOID Disease ST-elevation myocardial infarction Trial question What is the role of supplemental oxygen therapy in patients with STEMI? Study design Multi-center Open label RCT Population Characteristics of study participants 21.4% female N = 638 78.6% male 638 patients (93 female, 348 male) Inclusion criteria: patients with STEMI diagnosed on paramedic 12-lead ECG Key exclusion criteria: oxygen saturation < 94% measured on pulse oximeter, bronchospasm requiring nebulized salbutamol therapy with oxygen, oxygen administration before randomization, or altered conscious state Interventions N=318 routine supplemental oxygen (via face mask at 8 L/min) N=320 restricted supplemental oxygen (no oxygen unless oxygen saturation < 94%, in which case oxygen was administered via nasal cannula (4 L/min) or face mask (8 L/min) to achieve an oxygen saturation of 94%) https://web.pathway.md/studies/recHZYMVN3EP0vyhD 1/2 6/28/23, 12:50 AM AVOID Pathway Primary outcome Mean peak creatine kinase 1948.0 U/L 1948 1543 1461.0 U/L 974.0 U/L 487.0 U/L Significant increase 0.0 U/L Routine supplemental oxygen Restricted supplemental oxygen Significant increase in mean peak CK (1948 U/L vs. 1543 U/L; MR 1.27, 95% CI 1.04 to 1.52) Secondary outcomes Significant increase in recurrent myocardial infarction (5.5% vs. 0.9%; RR 6.1, 95% CI 1.75 to 10.45) No significant difference in geometric mean peak cTnI in patients with confirmed STEMI (57.4 g/L vs. 48 g/L; RR 1.2, 95% CI 0.92 to 1.56) Safety outcomes No significant differences in mortality at hospital discharge (1.8% vs. 4.5%, p=0.11). Conclusion In patients with STEMI diagnosed on paramedic 12-lead ECG, routine supplemental oxygen was inferior to restricted supplemental oxygen with respect to mean peak CK. Reference Stub D, Smith K, Bernard S et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation. 2015 Jun 16;131(24):2143-50. Open reference URL https://web.pathway.md/studies/recHZYMVN3EP0vyhD 2/2
6/28/23, 12:51 AM AXIOMATIC-TKR (high-dose) Pathway Feedback Search Clinical Topics Home Studies AXIOMATIC TKR (high-dose) AXIOMATIC TKR (high-dose) Disease Knee osteoarthritis Trial question What is the role of high-dose milvexian in the prevention of VTE in patients undergoing knee arthroplasty? Study design Multi-center Open label RCT Population Characteristics of study participants 68.0% female N = 383 32.0% male 383 patients (260 female, 123 male) Inclusion criteria: patients, aged 50 years, undergoing elective unilateral total knee arthroplasty Key exclusion criteria: contraindications to enoxaparin; history of severe hepatic impairment or previous VTE; long-term use of antithrombotic therapy other than aspirin; inability to undergo venography Interventions N=131 milvexian (at a dose of 200 mg BID) N=252 enoxaparin (at a dose of 40 mg once daily) Primary outcome https://web.pathway.md/studies/recUBhUYIFebmjQnN 1/2 6/28/23, 12:51 AM AXIOMATIC-TKR (high-dose) Pathway Venous thromboembolism 21.0 % 21 15.8 % 10.5 % 8 Significant decrease 5.3 % NNT = 8 0.0 % Milvexian Enoxaparin Significant decrease in VTE (8% vs. 21%; RR 0.37, 95% CI 0.19 to 0.69) Safety outcomes No significant differences in any bleeding, major bleeding or clinically relevant nonmajor bleeding. Conclusion In patients, aged 50 years, undergoing elective unilateral total knee arthroplasty, milvexian was superior to enoxaparin with respect to VTE. Reference Jeffrey I Weitz, John Strony, Walter Ageno et al. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021 Dec 2;385(23):2161-2172. Open reference URL https://web.pathway.md/studies/recUBhUYIFebmjQnN 2/2
6/28/23, 12:51 AM AZA-001 Pathway Feedback Search Clinical Topics Home Studies AZA 001 AZA 001 Disease Myelodysplastic syndrome Trial question What is the effect of azacitidine in patients with higher-risk myelodysplastic syndromes? Study design Multi-center Open label RCT Population Characteristics of study participants 30.0% female N = 358 70.0% male 358 patients (107 female, 251 male) Inclusion criteria: patients with higher-risk myelodysplastic syndromes Key exclusion criteria: therapy-related myelodysplastic syndrome, previous azacitidine treatment, or planned allogeneic stem-cell transplantation Interventions N=179 azacitidine (75 mg/m per day for 7 days every 28 days) N=179 conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy) Primary outcome Overall survival 24.5 24.5 https://web.pathway.md/studies/recurY9tid9NVwf5y 1/2 6/28/23, 12:51 AM AZA-001 Pathway 5 18.4 15 12.3 6.1 Significant increase 0.0 Azacitidine Conventional care Significant increase in overall survival (24.5 vs. 15; HR 1.72, 95% CI 1.3 to 2.33) Secondary outcomes Significant increase in median time to acute myeloid leukemia transformation (17.8 vs. 11.5; HR 2, 95% CI 1.43 to 2.86) Safety outcomes Significant differences in grade 3 or 4 toxicity, including neutropenia (91% vs. 76%), thrombocytopenia (85% vs. 80%) and anemia (57% vs. 68%). Conclusion In patients with higher-risk myelodysplastic syndromes, azacitidine was superior to conventional care with respect to overall survival. Reference Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. Open reference URL https://web.pathway.md/studies/recurY9tid9NVwf5y 2/2
6/28/23, 12:51 AM AZT Trial Pathway Feedback Search Clinical Topics Home Studies AZT Trial AZT Trial Disease Human immunodeficiency virus i Trial question What is the role of azidothymidine in patients with AIDS and AIDS-related complex? Study design Multi-center Double blinded RCT Population Characteristics of study participants 5.0% female N = 282 95.0% male 282 patients (13 female, 269 male) Inclusion criteria: patients with AIDS and AIDS-related complex Key exclusion criteria: multiple episodes of P. carinii pneumonia or any other opportunistic infection or neoplasm Interventions N=145 azidothymidine (250 mg PO every 4 hours for a total of 24 weeks) N=137 placebo (matching placebo PO every 4 hours for a total of 24 weeks) Primary outcome Death during study period 19.0 patient 19 https://web.pathway.md/studies/recVF3OoXo6P4eMnZ 1/2 6/28/23, 12:51 AM AZT Trial Pathway p 9 14.3 patient 9.5 patient 4.8 patient Significant decrease 1 0.0 patient Azidothymidine Placebo Significant decrease in death during the study period (1 patient vs. 19 patient; RR 0.05, 95% CI 0.02 to 0.08) Secondary outcomes Significant decrease in frequency of opportunistic infections (24 vs. 45; RR 0.53, 95% CI 0.22 to 0.84) Significant increase in CD4 cell count (0.96 vs. 0.7; RR 1.37, 95% CI 0.56 to 2.18) Significant increase in skin-test anergy reversal (29% vs. 9%; RR 3.22, 95% CI 1.31 to 5.13) Safety outcomes Significant differences in reversal of skin test anergy (29% vs. 9%, p < 0.001) and increase in the number of CD4 cells in AZT recipients than in placebo (p < 0.001). Conclusion In patients with AIDS and AIDS-related complex, azidothymidine was superior to placebo with respect to death during the study period. Reference Fischl MA, Richman DD, Grieco MH et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185-91. Open reference URL https://web.pathway.md/studies/recVF3OoXo6P4eMnZ 2/2
6/27/23, 11:40 PM BACC Pathway Feedback Search Clinical Topics Home Studies BACC BACC Disease COVID 19 infection Trial question What is the effect of tocilizumab in moderately ill patients hospitalized with COVID-19? Study design Multi-center Double blinded RCT Population Characteristics of study participants 42.0% female N = 243 58.0% male 243 patients (102 female, 141 male) Inclusion criteria: patients with confirmed SARS-CoV-2 infection, hyperinflammatory states, and at least two of the following signs: fever, pulmonary infiltrates, or the need for supplemental oxygen in order to maintain oxygen saturation > 92% Key exclusion criteria: receipt of supplemental oxygen at a rate > 10 L/min, a recent history of treatment with biologic agents or small-molecule immunosuppressive therapy, receipt of other immunosuppressive therapy that would increase risk of infection, diverticulitis Interventions N=161 tocilizumab (single dose of intravenous 8 mg per kg of body weight, not exceeding 800 mg plus standard care) N=82 placebo (a matching single dose of intravenous placebo plus standard care) Primary outcome Intubation or death at day 28 https://web.pathway.md/studies/recyPBsALjcNb2NTY 1/2 6/27/23, 11:40 PM BACC Pathway 12.5 % 12.5 10.6 9.4 % 6.3 % 3.1 % No significant difference 0.0 % Tocilizumab Placebo No significant difference in intubation or death at day 28 (10.6% vs. 12.5%; HR 0.83, 95% CI 0.38 to 1.81) Secondary outcomes No significant difference in clinical worsening of disease at 28 days (19.3% vs. 17.4%; HR 1.11, 95% CI 0.59 to 2.1) No significant difference in median time to discontinuation of supplemental oxygen by 28 days (5 days vs. 4.9 days; HR 0.94, 95% CI 0.67 to 1.3) No significant difference in mechanical ventilation (6.8% vs. 9.8%; HR 0.65, 95% CI 0.26 to 1.62) Safety outcomes No significant differences in death, myocardial infarction, thrombocytopenia, bleeding, stroke, seizure, PE or deep vein thrombosis. Significant differences in serious infections (8.1% vs. 17.1%), severe neutropenia (13.7% vs. 1.2%). Conclusion In patients with confirmed SARS-CoV-2 infection, hyperinflammatory states, and at least two of the following signs: fever, pulmonary infiltrates, or the need for supplemental oxygen in order to maintain oxygen saturation > 92%, tocilizumab was not superior to placebo with respect to intubation or death at day 28. Reference John H Stone, Matthew J Frigault, Naomi J Serling-Boyd et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Dec 10;383(24):2333-2344. Open reference URL https://web.pathway.md/studies/recyPBsALjcNb2NTY 2/2
6/27/23, 11:41 PM BALANCED Pathway Feedback Search Clinical Topics Home Studies BALANCED BALANCED Trial question What is the role of light general anesthesia among patients at increased risk of complications after major surgery? Study design Multi-center Single blinded RCT Population Characteristics of study participants 36.0% female N = 6644 64.0% male 6644 patients (2423 female, 4221 male) Inclusion criteria: patients with increased risk of complications after major surgery Key exclusion criteria: inability to place electrodes and monitor the bispectral index because of the site of surgery; planned wake-up test; use of nitrous oxide, propofol infusion for maintenance of anesthesia, or ketamine at an infusion rate > 25 mg/hour Interventions N=3316 light general anesthesia (bispectral index target 50) N=3328 deep general anesthesia (bispectral index target 35) Primary outcome Death from all causes at 1 year 7.2 % 7.2 6.5 5.4 % 3.6 % 1.8 % No significant difference 0.0 % Light general anesthesia Deep general anesthesia https://web.pathway.md/studies/recgCdregxGp5hfW6 1/2 6/27/23, 11:41 PM BALANCED Pathway No significant difference in death from all causes at 1 year (6.5% vs. 7.2%; HR 0.88, 95% CI 0.73 to 1.07) Secondary outcomes No significant difference in myocardial infarction (2% vs. 2%; HR 1, 95% CI 0.73 to 1.38) No significant difference in PE (1% vs. 1%; HR 0.77, 95% CI 0.49 to 1.22) Safety outcomes No significant difference in grade 3 and grade 4 adverse events. Conclusion In patients with increased risk of complications after major surgery, light general anesthesia was not superior to deep general anesthesia with respect to death from all causes at 1 year. Reference Timothy G Short, Douglas Campbell, Christopher Frampton et al. Anaesthetic depth and complications after major surgery: an international, randomised controlled trial. Lancet. 2019 Nov 23;394(10212):1907-1914. Open reference URL https://web.pathway.md/studies/recgCdregxGp5hfW6 2/2
6/27/23, 11:48 PM BaSICS Pathway Feedback Search Clinical Topics Home Studies BaSICS BaSICS Disease Acute kidney injury Trial question Is a balanced solution superior to 0.9% saline solution in critically ill patients requiring fluid challenges? Study design Multi-center Double blinded RCT Population Characteristics of study participants 44.0% female N = 10520 56.0% male 10520 patients (4650 female, 5870 male) Inclusion criteria: critically ill patients requiring fluid administration with 1 risk factors for worse outcomes Key exclusion criteria: AKI treated or expected to require RRT within the next 6 hours, severe electrolyte disturbance, imminent death within 24 hours, brain death, receipt of palliative care Interventions N=5522 balanced solution (Plasma-Lyte) N=5530 saline solution (0.9% sodium chloride) Primary outcome Deaths at day 90 27.2 % 27.2 26.4 20 4 % https://web.pathway.md/studies/rec39fjNmuU1GSrw9 1/2 6/27/23, 11:48 PM 20.4 % BaSICS Pathway 13.6 % 6.8 % No significant difference 0.0 % Balanced solution Saline solution No significant difference in deaths at day 90 (26.4% vs. 27.2%; aHR 0.97, 95% CI 0.9 to 1.05) Secondary outcomes No significant difference in need for RRT in the hospital (7.5% vs. 8.1%; OR 0.93, 95% CI 0.81 to 1.06) No significant difference in AKI with KDIGO stage 2 at day 7 (23.4% vs. 23.3%; OR 1.07, 95% CI 0.88 to 1.3) No significant difference in hospital length of stay (8 days vs. 9 days; AD -0.3 days, 95% CI -1.1 to 0.5) Conclusion In critically ill patients requiring fluid administration with 1 risk factors for worse outcomes, balanced solution was not superior to saline solution with respect to deaths at day 90. Reference Fernando G Zampieri, Fl via R Machado, Rodrigo S Biondi et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA. 2021 Aug 10;326(9):1-12. Open reference URL https://web.pathway.md/studies/rec39fjNmuU1GSrw9 2/2
6/27/23, 11:42 PM BAT Pathway Feedback Search Clinical Topics Home Studies BAT BAT Disease Bronchiectasis Trial question What is the role of azithromycin maintenance treatment on infectious exacerbations in adult patients with non-cystic fibrosis bronchiectasis? Study design Multi-center Double blinded RCT Population Characteristics of study participants 64.0% female N = 83 36.0% male 83 patients (53 female, 30 male) Inclusion criteria: adult patients with non-cystic fibrosis bronchiectasis and 3 lower respiratory tract infections in the preceding year Key exclusion criteria: prolonged (> 4 weeks) macrolide therapy during the previous 3 months, oral or intravenous courses of corticosteroids within 30 days of screening, any antimicrobial treatment for an LRTI in the last 2 weeks, known allergy or intolerance to macrolides, or patients with liver disease Interventions N=43 azithromycin (250 mg daily for 12 months) N=40 placebo (matching placebo daily for 12 months) Primary outcome Exacerbation, at least 1 https://web.pathway.md/studies/rectmdCVACPCmmUcP 1/2 6/27/23, 11:42 PM BAT Pathway 80.0 % 80 60.0 % 46 40.0 % 20.0 % Borderline significant decrease 0.0 % Azithromycin Placebo Borderline significant decrease in exacerbation, at least 1 (46% vs. 80%; HR 0.29, 95% CI 0.16 to 0.51) Safety outcomes Significant differences in gastrointestinal adverse effects (40% vs 5%), including abdominal pain (19% vs. 3%) and diarrhea (21% vs. 3%) and macrolide resistance (88% vs. 26%). Conclusion In adult patients with non-cystic fibrosis bronchiectasis and 3 lower respiratory tract infections in the preceding year, azithromycin was superior to placebo with respect to exacerbation, at least 1. Reference Altenburg J, de Graaff CS, Stienstra Y et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013 Mar 27;309(12):1251-9. Open reference URL https://web.pathway.md/studies/rectmdCVACPCmmUcP 2/2
6/27/23, 11:42 PM BCG-PRIME Pathway Feedback Search Clinical Topics Home Studies BCG PRIME BCG PRIME Disease COVID 19 infection Trial question What is the role of BCG vaccine in older adults with underlying comorbidities? Study design Multi-center Double blinded RCT Population Characteristics of study participants 37.0% female N = 6112 63.0% male 6112 patients (2275 female, 3837 male) Inclusion criteria: adults > 60 years of age with 1 underlying comorbidities and no contraindications for BCG vaccination Key exclusion criteria: history of documented COVID-19; known history of a positive Mantoux or active tuberculosis; severely immunocompromised state; vaccination with a live vaccine in the past 4 weeks, or planned vaccination with a live vaccine during the next 4 weeks Interventions N=3058 BCG (0.1 mL of BCG vaccine via intradermal injection in the left upper arm) N=3054 placebo (0.1 mL saline via intradermal injection in the left upper arm) Primary outcome COVID-19 infection 4.2 % 4.2 3.8 3 2 % https://web.pathway.md/studies/recUroOupT9fxVA2W 1/2 6/27/23, 11:42 PM BCG-PRIME Pathway 3.2 % 2.1 % 1.1 % No significant difference 0.0 % BCG Placebo No significant difference in COVID-19 infection (4.2% vs. 3.8%; HR 1.12, 95% CI 0.87 to 1.44) Secondary outcomes No significant difference in COVID-19-related hospitalization (0.6% vs. 0.7%; HR 0.86, 95% CI 0.46 to 1.61) No significant difference in clinically relevant respiratory tract infection (2.2% vs. 2.4%; HR 0.92, 95% CI 0.66 to 1.28) No significant difference in respiratory tract infection-related hospital admission (0.85% vs. 0.94%; HR 0.9, 95% CI 0.53 to 1.53) Safety outcomes No significant difference in death from all causes at 6 months. Conclusion In adults > 60 years of age with 1 underlying comorbidities and no contraindications for BCG vaccination, BCG was not superior to placebo with respect to a COVID-19 infection. Reference writing committee for the BCG-PRIME study group, Writing committee, Eva L Koekenbier et al. Bacillus Calmette-Gu rin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial. Clin Microbiol Infect. 2023 Jan 31;S1198-743X(23)00044-7. Open reference URL https://web.pathway.md/studies/recUroOupT9fxVA2W 2/2
6/27/23, 11:42 PM BEAMS (morphine 16 mg) Pathway Feedback Search Clinical Topics Home Studies BEAMS (morphine 16 mg) BEAMS (morphine 16 mg) Disease Disease Chronic obstructive pulmonary Dyspnea in palliative care Trial question What is the effect of ER morphine in patients with COPD? Study design Multi-center Double blinded RCT Population Characteristics of study participants 48.0% female N = 101 52.0% male 101 patients (48 female, 53 male) Inclusion criteria: adult patients with COPD and chronic breathlessness Key exclusion criteria: receipt of opioids; morphine allergy; central hypoventilation syndrome; pregnancy; liver or kidney failure Interventions N=51 morphine (at an ER oral dose of 16 mg/day) N=50 placebo (matching placebo given daily) Primary outcome Reduction in intensity of worst breathlessness at week 1 1.0 1 0.8 0.7 0 5 https://web.pathway.md/studies/recUnIkfyNP85Y49a 1/2 6/27/23, 11:42 PM BEAMS (morphine 16 mg) Pathway 0.5 0.3 No significant difference 0.0 Morphine Placebo No significant difference in reduction in intensity of worst breathlessness at week 1 (1 vs. 0.7; AD 0.3, 95% CI -0.4 to 1) Secondary outcomes Significant increase in reduction in daily step count at week 1 (399 vs. -99; AD 388, 95% CI -277 to -1053) No significant difference in reduction in overall breathlessness distress level at week 1 (1.3 vs. 0.7; AD 0.4, 95% CI -0.4 to 1.2) Safety outcomes No significant differences in nausea, anxiety, dyspnea. Conclusion In adult patients with COPD and chronic breathlessness, morphine was not superior to placebo with respect to reduction in intensity of worst breathlessness at week 1. Reference Magnus Ekstr m, Diana Ferreira, Sungwon Chang et al. Effect of Regular, Low-Dose, Extended- release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial. JAMA. 2022 Nov 22;328(20):2022-2032. Open reference URL https://web.pathway.md/studies/recUnIkfyNP85Y49a 2/2
6/27/23, 11:43 PM BEAMS (morphine 8 mg) Pathway Feedback Search Clinical Topics Home Studies BEAMS (morphine 8 mg) BEAMS (morphine 8 mg) Disease Disease Chronic obstructive pulmonary Dyspnea in palliative care Trial question What is the effect of ER morphine in patients with COPD? Study design Multi-center Double blinded RCT Population Characteristics of study participants 47.0% female N = 105 53.0% male 105 patients (49 female, 56 male) Inclusion criteria: adult patients with COPD and chronic breathlessness Key exclusion criteria: receipt of opioids; morphine allergy; central hypoventilation syndrome; pregnancy; liver or kidney failure Interventions N=55 morphine (at an ER oral dose of 8 mg/day) N=50 placebo (matching placebo daily) Primary outcome Reduction in intensity of worst breathlessness at week 1 0.8 0.8 0.7 0.6 0.4 https://web.pathway.md/studies/recRBBRGg9dXDUSX7 1/2 6/27/23, 11:43 PM BEAMS (morphine 8 mg) Pathway 0 0.2 No significant difference 0.0 Morphine Placebo No significant difference in reduction in intensity of worst breathlessness at week 1 (0.8 vs. 0.7; AD 0.3, 95% CI -0.4 to 0.9) Secondary outcomes No significant difference in reduction in daily step count at week 1 (84 vs. 99; AD 39, 95% CI -501 to 579) No significant difference in reduction in intensity of breathlessness at week 1 (0.6 vs. 0.6; AD 0.1, 95% CI -0.5 to 0.7) No significant difference in reduction in overall breathlessness distress level at week 1 (1 vs. 0.7; AD 0.4, 95% CI -0.4 to 1.1) Safety outcomes No significant differences in anxiety, dyspnea, nausea. Conclusion In adult patients with COPD and chronic breathlessness, morphine was not superior to placebo with respect to reduction in intensity of worst breathlessness at week 1. Reference Magnus Ekstr m, Diana Ferreira, Sungwon Chang et al. Effect of Regular, Low-Dose, Extended- release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial. JAMA. 2022 Nov 22;328(20):2022-2032. Open reference URL https://web.pathway.md/studies/recRBBRGg9dXDUSX7 2/2
6/27/23, 11:48 PM Benazepril in Severe CKD Pathway Feedback Search Clinical Topics Home Studies Benazepril in Severe CKD Benazepril in Severe CKD Disease Chronic kidney disease Trial question What is the role of benazepril in patients without diabetes who had advanced renal insufficiency? Study design Single center Double blinded RCT Population Characteristics of study participants 50.0% female N = 224 50.0% male 224 patients (113 female, 111 male) Inclusion criteria: patients without diabetes who had advanced renal insufficiency Key exclusion criteria: immediate need for dialysis; treatment with corticosteroids, non- steroidal anti-inflammatory drugs or immunosuppressive drugs; renovascular disease; myocardial infarction; connective-tissue disease; obstructive uropathy Interventions N=112 benazepril (20 mg per day) N=112 placebo (matching placebo per day) Primary outcome Death, end-stage renal disease, or doubling of serum creatinine 60 60.0 % 45.0 % 41 https://web.pathway.md/studies/recZ5wcYkSOULP3z7 1/2 6/27/23, 11:48 PM Benazepril in Severe CKD Pathway 41 30.0 % Significant decrease 15.0 % NNT = 5 0.0 % Benazepril Placebo Significant decrease in death, end-stage renal disease, or doubling of the serum creatinine (41% vs. 60%; RR 0.68, 95% CI 0.22 to 1.14) Secondary outcomes Significant increase in the percentage of patients achieving a reduction in proteinuria (52% vs. 20%; RR 2.6, 95% CI 1.06 to 4.14) Safety outcomes No significant difference in major adverse events. Conclusion In patients without diabetes who had advanced renal insufficiency, benazepril was superior to placebo with respect to death, end-stage renal disease, or doubling of the serum creatinine. Reference Hou FF, Zhang X, Zhang GH et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006 Jan 12;354(2):131-40. Open reference URL https://web.pathway.md/studies/recZ5wcYkSOULP3z7 2/2
6/27/23, 11:43 PM BERLIN-VT Pathway Feedback Search Clinical Topics Home Studies BERLIN VT BERLIN VT Disease Disease Disease Coronary artery disease Dilated cardiomyopathy Ventric Trial question Is preventive ablation strategy superior to deferred ablation strategy in patients with ischemic cardiomyopathy and implantable defibrillator? Study design Multi-center Open label RCT Population Characteristics of study participants 13.0% female N = 159 87.0% male 159 patients (20 female, 139 male) Inclusion criteria: patients with stable ischemic cardiomyopathy, a LVEF between 30-50%, and VT Key exclusion criteria: age < 18 years or > 80 years; arterial or venous thrombosis; acute myocardial reinfarction; acute coronary syndrome; requirement of chronic renal dialysis Interventions N=76 preventive ablation (prophylactic VT ablation prior to ICD implantation) N=83 deferred ablation (catheter ablation after the third appropriate ICD shock) Primary outcome Composite of death and unplanned hospitalization for symptomatic ventricular arrhythmia or worsening heart failure 32.9 % 32.9 https://web.pathway.md/studies/rec2fFHW3Ko8gj3Zo 1/2 6/27/23, 11:43 PM BERLIN-VT Pathway 27.7 24.7 % 16.4 % 8.2 % No significant difference 0.0 % Preventive ablation Deferred ablation No significant difference in composite of death and unplanned hospitalization for symptomatic ventricular arrhythmia or worsening HF (32.9% vs. 27.7%; HR 1.09, 95% CI 0.62 to 1.92) Secondary outcomes Borderline significant decrease in sustained ventricular tachyarrhythmia (39.7% vs. 48.2%; HR 0.62, 95% CI 0.38 to 1) Significant decrease in appropriate ICD therapy (34.2% vs. 47%; HR 0.55, 95% CI 0.33 to 0.91) Significant decrease in appropriate antitachycardia pacing (34.2% vs. 45.8%; HR 0.57, 95% CI 0.34 to 0.95) Safety outcomes No significant differences in death, unplanned hospitalization. Conclusion In patients with stable ischemic cardiomyopathy, a LVEF between 30-50%, and VT, preventive ablation was not superior to deferred ablation with respect to the composite of death and unplanned hospitalization for symptomatic ventricular arrhythmia or worsening HF. Reference Stephan Willems, Roland Richard Tilz, Daniel Steven et al. Preventive or Deferred Ablation of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy and Implantable Defibrillator (BERLIN VT): A Multicenter Randomized Trial. Circulation. 2020 Mar 31;141(13):1057-1067. Open reference URL https://web.pathway.md/studies/rec2fFHW3Ko8gj3Zo 2/2
6/27/23, 11:43 PM BEST Pathway Feedback Search Clinical Topics Home Studies BEST BEST Disease Coronary artery disease Trial question What is the role of everolimus-eluting stents in patients with multivessel coronary artery disease? Study design Multi-center Open label RCT Population Characteristics of study participants 29.0% female N = 880 71.0% male 880 patients (251 female, 629 male) Inclusion criteria: patients with multivessel coronary artery disease Key exclusion criteria: known hypersensitivity to heparin, aspirin, clopidogrel, everolimus, stainless steel and/or contrast media; severe congestive HF; previous bypass surgery; acute STEMI; abnormal CK; prior history of significant bleeding; contraindication to either CABG or PCI/DES; suspected pregnancy; or left main coronary artery stenosis 50% diameter Interventions N=438 PCI (with everolimus-eluting stents) N=442 CABG (standard surgical procedure) Primary outcome Death, myocardial infarction, or target-vessel revascularization 15.3 % 15.3 https://web.pathway.md/studies/recTjVFCb0Fn2Qiy6 1/2 6/27/23, 11:43 PM BEST Pathway 11.5 % 10.6 7.7 % Difference exceeding nonferiority margin 3.8 % 0.0 % Percutaneous coronary intervention Coronary artery bypass graft Difference exceeding nonferiority margin in death, myocardial infarction, or target-vessel revascularization (15.3% vs. 10.6%; HR 1.47, 95% CI 1.01 to 2.13) Secondary outcomes No significant difference in myocardial infarction (4.8% vs. 2.7%; HR 1.76, 95% CI 0.87 to 3.58) Significant increase in death, myocardial infarction, stroke, or repeat revascularization (19.9% vs. 13.3%; HR 1.54, 95% CI 1.11 to 2.14) No significant difference in death from any cause (6.6% vs. 5%; HR 1.34, 95% CI 0.77 to 2.34) Safety outcomes No significant difference in fatal bleeding. Significant difference in major bleeding (6.8% vs. 29.9%). Conclusion In patients with multivessel coronary artery disease, PCI was not noninferior to CABG with respect to death, myocardial infarction, or target-vessel revascularization. Reference Park SJ, Ahn JM, Kim YH et al. Trial of everolimus-eluting stents or bypass surgery for coronary disease. N Engl J Med. 2015 Mar 26;372(13):1204-12. Open reference URL https://web.pathway.md/studies/recTjVFCb0Fn2Qiy6 2/2
6/27/23, 11:43 PM BICAR-ICU Pathway Feedback Search Clinical Topics Home Studies BICAR ICU BICAR ICU Disease Metabolic acidosis Trial question What is the role of sodium bicarbonate therapy among ICU patients with severe metabolic acidemia? Study design Multi-center Open label RCT Population Characteristics of study participants 38.8% female N = 400 61.2% male 400 patients (151 female, 238 male) Inclusion criteria: adult patients admitted to the ICU within 48 hours experiencing severe acidemia and a total Sequential Organ Failure Assessment score 4 or an arterial lactate concentration 2 mmol/L Key exclusion criteria: respiratory acidosis, proven digestive or urinary tract loss of sodium bicarbonate, stage IV CKD, ketoacidosis, and sodium bicarbonate infusion within 24 h before the screening Interventions N=195 bicarbonate (4.2% of intravenous sodium bicarbonate infusion) N=194 control (no sodium bicarbonate) Primary outcome Death from any cause by day 28 and presence of at least one organ failure at day 7 https://web.pathway.md/studies/recjbv8hbMdJ0MOla 1/2 6/27/23, 11:43 PM BICAR-ICU Pathway 71.0 % 71 66 53.3 % 35.5 % 17.8 % No significant difference 0.0 % Bicarbonate Control No significant difference in death from any cause by day 28 and the presence of at least one organ failure at day 7 (66% vs. 71%; ARD -5.5, 95% CI -15.2 to 4.2) Secondary outcomes Significant decrease in death by day 28 and the presence of at least one organ failure at day 7 in patients with AKI scores of 2-3 (70% vs. 82%; ARD -12.3, 95% CI -26 to -0.1) No significant difference in dependence on dialysis at ICU discharge (22% vs. 34%; ARD -12.5, 95% CI -34.3 to 9.3) Safety outcomes No significant difference in ICU-acquired infections. Significant difference in RRT during ICU stay (35% vs. 52%). Conclusion In adult patients admitted to the ICU within 48 hours experiencing severe acidemia and a total Sequential Organ Failure Assessment score 4 or an arterial lactate concentration 2 mmol/L, bicarbonate was not superior to control with respect to death from any cause by day 28 and the presence of at least one organ failure at day 7. Reference Samir Jaber, Catherine Paugam, Emmanuel Futier et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018 Jul 7;392(10141):31-40. Open reference URL https://web.pathway.md/studies/recjbv8hbMdJ0MOla 2/2
6/27/23, 11:44 PM BILEVEL-APRV Pathway Feedback Search Clinical Topics Home Studies BILEVEL APRV BILEVEL APRV Disease Acute respiratory distress syndr Trial question What is the effect of early application of airway pressure release ventilation in patients with ARDS? Study design Single center Open label RCT Population Characteristics of study participants 34.0% female N = 138 66.0% male 138 patients (47 female, 91 male) Inclusion criteria: patients with ARDS who received mechanical ventilation for < 48 hours Key exclusion criteria: anticipated duration of invasive mechanical ventilation < 48 hours; intracranial hypertension; severe COPD; barotrauma; refractory shock; pregnancy Interventions N=71 airway pressure release ventilation (bi-level airway pressure ventilation-airway pressure release ventilation mode, combination with spontaneous breathing) N=67 low tidal volume lung protective ventilation (volume-controlled ventilation or pressure- controlled ventilation mode combination with adequate PEEP level) Primary outcome Number of days without mechanical ventilation at 28 days 19.0 days 19 https://web.pathway.md/studies/recC3ZpeuG3hEoaFD 1/2 6/27/23, 11:44 PM BILEVEL-APRV Pathway 14.3 days 9.5 days 4.8 days Significant increase 2 0.0 days Airway pressure release ventilation Low tidal volume lung protective ventilation Significant increase in the number of days without mechanical ventilation at 28 days (19 days vs. 2 days; AD 17 days, 95% CI 6.91 to 27.09) Secondary outcomes No significant difference in death during ICU stay (19.7% vs. 34.3%; RR 0.57, 95% CI -0.01 to 1.15) Significant decrease in length of ICU stay (15 days vs. 20 days; AD -5 days, 95% CI -9.03 to -0.97) No significant difference in length of hospital stay (21 days vs. 27 days; AD -6 days, 95% CI -12.14 to 0.14) Safety outcomes No significant differences in pneumothorax between day 1 and day 28, receipt of inhaled nitric oxide, and high-frequency oscillatory ventilation. Significant differences in successful extubation (66.2% vs. 38.8%), tracheostomy (12.7% vs. 29.9%), and receipt of neuromuscular blockers (2.8% vs. 13.4%). Conclusion In patients with ARDS who received mechanical ventilation for < 48 hours, airway pressure release ventilation was superior to low tidal volume lung protective ventilation with respect to number of days without mechanical ventilation at 28 days. Reference Yongfang Zhou, Xiaodong Jin, Yinxia Lv et al. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017 Nov;43(11):1648-1659. Open reference URL https://web.pathway.md/studies/recC3ZpeuG3hEoaFD 2/2
6/27/23, 11:44 PM BLESS Pathway Feedback Search Clinical Topics Home Studies BLESS BLESS Disease Bronchiectasis Trial question What is the role of low-dose erythromycin in patients with non-cystic fibrosis bronchiectasis? Study design Multi-center Double blinded RCT Population Characteristics of study participants 58.8% female N = 679 41.2% male 679 patients (71 female, 46 male) Inclusion criteria: patients with non-cystic fibrosis bronchiectasis with a history of 2 infective exacerbations in the preceding year Key exclusion criteria: CF, current mycobacterial disease or bronchopulmonary aspergillosis, reversible cause for exacerbations, maintenance oral antibiotic prophylaxis, prior macrolide use except short-term, or cigarette smoking within 6 months Interventions N=59 erythromycin (BID erythromycin ethylsuccinate 400 mg for 48 weeks, followed by a 4- weeks washout period) N=58 placebo (matching placebo BID) Primary outcome Pulmonary exacerbations 2.0/ p-y 1.97 https://web.pathway.md/studies/rec7OmJ0SRuvEoTOt 1/2 6/27/23, 11:44 PM BLESS Pathway 1.5/ p-y 1.29 1.0/ p-y 0.5/ p-y Significant decrease 0.0/ p-y Erythromycin Placebo Significant decrease in pulmonary exacerbations (1.29 / p-y vs. 1.97 / p-y; IRR 0.57, 95% CI 0.42 to 0.77) Secondary outcomes Significant increase in macrolide-resistant oropharyngeal streptococci (27.7% vs. 0.04%; AD 25.5%, 95% CI 10.37 to 40.63) Safety outcomes Significant difference in adverse events (28.8% vs. 25.9%). Conclusion In patients with non-cystic fibrosis bronchiectasis with a history of 2 infective exacerbations in the preceding year, erythromycin was superior to placebo with respect to pulmonary exacerbations. Reference Serisier DJ, Martin ML, McGuckin MA et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA. 2013 Mar 27;309(12):1260-7. Open reference URL https://web.pathway.md/studies/rec7OmJ0SRuvEoTOt 2/2
6/27/23, 11:44 PM BLOCK-HF Pathway Feedback Search Clinical Topics Home Studies BLOCK HF BLOCK HF Disease Heart failure Trial question What is the role of biventricular pacing in patients with AV block and LV systolic dysfunction? Study design Multi-center Double blinded RCT Population Characteristics of study participants 25.3% female N = 918 74.7% male 918 patients (174 female, 517 male) Inclusion criteria: patients with AV block with NYHA class I-III HF and LVEF 50% Key exclusion criteria: previous receipt of a cardiac implantable electrical device, unstable angina, acute myocardial infarction, percutaneous or surgical coronary intervention within 30 days before enrollment, valvular disease with an indication for valve repair or replacement Interventions N=349 biventricular pacing (cardiac-resynchronization pacemaker or ICD with pacing of both the ventricles) N=342 conventional RV pacing (cardiac-resynchronization pacemaker or ICD with pacing of only the right ventricle) Primary outcome Death, urgent care visit for heart failure, or 15% elevation in left ventricular end-systolic volume index https://web.pathway.md/studies/recTUhh6qgdfkv8Wb 1/2 6/27/23, 11:44 PM BLOCK-HF Pathway 55.6 % 55.6 45.8 41.7 % 27.8 % 13.9 % Borderline significant decrease 0.0 % Biventricular pacing Conventional right ventricular pacing Borderline significant decrease in death, urgent care visit for HF, or 15% elevation in the LV end-systolic volume index (45.8% vs. 55.6%; HR 0.74, 95% CI 0.6 to 0.9) Safety outcomes Significant difference in LV lead-related complications (6.4%). Conclusion In patients with AV block with NYHA class I-III HF and LVEF 50%, biventricular pacing was superior to conventional RV pacing with respect to death, urgent care visit for HF, or 15% elevation in the LV end-systolic volume index. Reference Curtis AB, Worley SJ, Adamson PB et al. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med. 2013 Apr 25;368(17):1585-93. Open reference URL https://web.pathway.md/studies/recTUhh6qgdfkv8Wb 2/2
6/27/23, 11:48 PM Blood Pressure Reduction in Black Barbershops Pathway Feedback Search Clinical Topics Home Studies Blood Pressure Reduction in Black Barbershops Blood Pressure Reduction in Black Barbershops Disease Hypertension Trial question What is the effect of BP intervention in black male patrons with uncontrolled hypertension, systolic BP 140 mmHg from black-owned barbershops (a nontraditional healthcare setting)? Study design Multi-center Open label RCT Population 319 male patients Inclusion criteria: black male patrons with uncontrolled hypertension, systolic BP of 140 mmHg from black-owned barbershops, a nontraditional healthcare setting Key exclusion criteria: women, persons receiving dialysis or chemotherapy, an age < 35 years or > 79 years, plans to relocate or infrequent barbershop patronage Interventions N=132 medication management in barbershops (by specialty-trained pharmacists) N=171 active control (encouragement of lifestyle modification and doctor appointments by barbers) Primary outcome Mean systolic blood pressure reduction at 6 months 27.0 mmHg 27 20.3 mmHg 13.5 mmHg 9.3 6.8 mmHg Significant increase https://web.pathway.md/studies/recioaGKUYkAQscXH 1/2 6/27/23, 11:48 PM Blood Pressure Reduction in Black Barbershops Pathway 0.0 mmHg Medication management in barbershops Active control Significant increase in mean systolic BP reduction at 6 months (27 mmHg vs. 9.3 mmHg; MD 17.7, 95% CI 14.7 to 28.4) Safety outcomes No significant difference in changes in medication side effects and no treatment-related serious adverse events were noted; transient AKI was reported in the intervention group. Conclusion In black male patrons with uncontrolled hypertension, systolic BP of 140 mmHg from black- owned barbershops, a nontraditional healthcare setting, medication management in barbershops were superior to active control with respect to mean systolic BP reduction at 6 months. Reference Victor RG, Lynch K, Li N et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. N Engl J Med. 2018 Apr 5;378(14):1291-1301. Open reference URL https://web.pathway.md/studies/recioaGKUYkAQscXH 2/2
6/27/23, 11:44 PM BOREAS Pathway Feedback Search Clinical Topics Home Studies BOREAS BOREAS Disease Chronic obstructive pulmonary Trial question What is the role of dupilumab in patients with COPD who had type 2 inflammation indicated by eosinophil counts? Study design Multi-center Double blinded RCT Population Characteristics of study participants 34.0% female N = 939 66.0% male 939 patients (319 female, 620 male) Inclusion criteria: patients with COPD who had a blood eosinophil count 300 cells/mL and an elevated exacerbation risk despite the use of standard triple therapy Key exclusion criteria: current diagnosis of asthma or a history of asthma Interventions N=468 dupilumab (subcutaneous injection of 300 mg every 2 weeks) N=471 placebo (matching placebo every 2 weeks) Primary outcome Annualized rate of moderate or severe exacerbations 1.1 1.1 0.8 0.78 https://web.pathway.md/studies/recoGNOSn5RCHsQf0 1/2 6/27/23, 11:44 PM BOREAS Pathway 0.6 0.3 Significant decrease 0.0 Dupilumab Placebo Significant decrease in annualized rate of moderate or severe exacerbations (0.78 vs. 1.1; RR 0.7, 95% CI 0.58 to 0.86) Secondary outcomes Significant increase in improvement in prebronchodilator FEV in 1 second at week 12 (160 mL vs. 77 mL; LSMD 83, 95% CI 42 to 125) Significant decrease in reduction in St. George's Respiratory Questionnaire Score at week 52 (-9.7 vs. -6.4; LSMD -3.4, 95% CI -5.5 to -1.3) Significant decrease in reduction in evaluating respiratory symptoms in COPD score (-2.7 vs. -1.6; LSMD -1.1, 95% CI -1.8 to -0.4) Safety outcomes No significant differences in adverse events leading to discontinuation of trial drug, serious adverse events, and adverse events leading to death. Conclusion In patients with COPD who had a blood eosinophil count 300 cells/mL and an elevated exacerbation risk despite the use of standard triple therapy, dupilumab was superior to placebo with respect to annualized rate of moderate or severe exacerbations. Reference Surya P Bhatt, Klaus F Rabe, Nicola A Hanania et al. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023 May 21. Online ahead of print. Open reference URL https://web.pathway.md/studies/recoGNOSn5RCHsQf0 2/2
6/27/23, 11:45 PM BOUGIE Pathway Feedback Search Clinical Topics Home Studies BOUGIE BOUGIE Trial question Is the use of bougie superior to an endotracheal tube with stylet in critically ill adults undergoing tracheal intubation? Study design Multi-center Open label RCT Population Characteristics of study participants 41.0% female N = 1102 59.0% male 1102 patients (452 female, 650 male) Inclusion criteria: critically ill adult patients undergoing tracheal intubation Key exclusion criteria: pregnancy, incarceration, immediate need for tracheal intubation without time for randomization, operator determines that use of a bougie or a stylet is required or contraindicated Interventions N=556 bougie (use of bougie for the first attempt at tracheal intubation) N=546 stylet (use of endotracheal tube with a malleable stylet for the first attempt at tracheal intubation) Primary outcome Successful intubation on first attempt 83.0 % 83 80.4 62.3 % 41.5 % 20.8 % No significant difference 0.0 % https://web.pathway.md/studies/recXEjaZ4oSlSqeK3 1/2 6/27/23, 11:45 PM BOUGIE Pathway Bougie Stylet No significant difference in successful intubation on the first attempt (80.4% vs. 83%; ARD -2.6, 95% CI -7.3 to 2.2) Secondary outcomes No significant difference in severe hypoxemia (11% vs. 8.8%; ARD 2.2, 95% CI -1.6 to 6) Significant decrease in the rate of death before 28 days (27.3% vs. 33.7%; ARD -6.4, 95% CI -12 to -0.8) No significant difference in ventilator-free days (24 days vs. 22 days; DIM 2, 95% CI 0.5 to 6) Safety outcomes No significant differences in airway complications, pneumothorax after intubation. Conclusion In critically ill adult patients undergoing tracheal intubation, bougie was not superior to stylet with respect to successful intubation on the first attempt. Reference Brian E Driver, Matthew W Semler, Wesley H Self et al. Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial. JAMA. 2021 Dec 28;326(24):2488-2497. Open reference URL https://web.pathway.md/studies/recXEjaZ4oSlSqeK3 2/2
6/27/23, 11:45 PM BOX Pathway Feedback Search Clinical Topics Home Studies BOX BOX Disease Cardiac arrest Trial question Is high BP target superior to low BP target in comatose survivors of cardiac arrest? Study design Multi-center Double blinded RCT Population Characteristics of study participants 19.0% female N = 789 81.0% male 789 patients (153 female, 636 male) Inclusion criteria: comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause Key exclusion criteria: known bleeding diathesis; unwitnessed asystole; suspected acute intracranial bleeding; stroke Interventions N=393 high BP target (targeting a mean arterial BP of 77 mmHg) N=396 low BP target (targeting a mean arterial BP of 63 mmHg) Primary outcome Death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 at day 90 34.0 % 34 32 25 5 % https://web.pathway.md/studies/recmzOQN2EwZzQcra 1/2 6/27/23, 11:45 PM 25.5 % BOX Pathway 17.0 % 8.5 % No significant difference 0.0 % High blood pressure target Low blood pressure target No significant difference in death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 at day 90 (34% vs. 32%; HR 1.08, 95% CI 0.84 to 1.37) Secondary outcomes No significant difference in death from any cause at day 90 (31% vs. 29%; HR 1.13, 95% CI 0.88 to 1.46) No significant difference in AKI with RRT (10% vs. 10%; HR 1.03, 95% CI 0.66 to 1.59) Safety outcomes No significant difference in serious adverse events. Conclusion In comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause, high BP target was not superior to low BP target with respect to death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 at day 90. Reference Jesper Kjaergaard, Jacob E M ller, Henrik Schmidt et al. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med. 2022 Oct 20;387(16):1456-1466. Open reference URL https://web.pathway.md/studies/recmzOQN2EwZzQcra 2/2
6/27/23, 11:46 PM BP-TARGET Pathway Feedback Search Clinical Topics Home Studies BP TARGET BP TARGET Disease Acute ischemic stroke Trial question What is the role of intensive systolic BP target after successful endovascular therapy in acute ischemic stroke? Study design Multi-center Open label RCT Population Characteristics of study participants 52.0% female N = 318 48.0% male 318 patients (165 female, 153 male) Inclusion criteria: adults with an acute ischemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy Key exclusion criteria: per-procedure hemorrhagic complications; systolic BP at baseline < 130 mm Hg within 1 hour of recanalization; pre-existing stroke disability defined by a mRS score > 2 Interventions N=158 intensive systolic BP target (systolic BP target of 100-129 mm Hg) N=160 standard systolic BP target (systolic BP target of 130-185 mm Hg) Primary outcome Radiographic intraparenchymal hemorrhage at 24-36 hours 43 43.0 % 42 https://web.pathway.md/studies/recshUsqEfTr8oaWf 1/2 6/27/23, 11:46 PM BP-TARGET Pathway 32.3 % 21.5 % 10.8 % No significant difference 0.0 % Intensive systolic blood pressure target Standard systolic blood pressure target No significant difference in radiographic intraparenchymal hemorrhage at 24-36 hours (42% vs. 43%; OR 0.96, 96% CI 0.6 to 1.51) Secondary outcomes No significant difference in favorable outcome at 3 months (44% vs. 45%; OR 0.93, 95% CI 0.58 to 1.48) No significant difference in excellent outcome at 3 months (32% vs. 28%; OR 1.2, 95% CI 0.72 to 1.97) No significant difference in reduction in NIHSS score at 24-36 hours (4.1 vs. 4.4; AD -0.3, 95% CI -1.7 to 2.3) Safety outcomes No significant differences in death from all causes, parenchymal hematoma type 2 at 24-36 hours. Significant difference in hypotension (8% vs. 3%). Conclusion In adults with an acute ischemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy, intensive systolic BP target was not superior to standard systolic BP target with respect to radiographic intraparenchymal hemorrhage at 24-36 hours. Reference Mikael Mazighi, Sebastien Richard, Bertrand Lapergue et al. Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP- TARGET): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2021 Apr;20(4):265-274. Open reference URL https://web.pathway.md/studies/recshUsqEfTr8oaWf 2/2
6/27/23, 11:46 PM BRACE Pathway Feedback Search Clinical Topics Home Studies BRACE BRACE Disease COVID 19 infection Trial question What is the role of the BCG vaccine in healthcare workers? Study design Multi-center Double blinded RCT Population Characteristics of study participants 75.0% female N = 3386 25.0% male 3386 patients (2526 female, 860 male) Inclusion criteria: healthcare workers Key exclusion criteria: previous positive SARS-CoV-2 test; contraindication to BCG vaccine; receipt of BCG vaccine within the past year; any other live-attenuated vaccine within the past month Interventions N=1703 BCG vaccine (receipt of BCG-Denmark vaccine with a follow-up for 12 months) N=1683 placebo (receipt of matching placebo with a follow-up for 12 months) Primary outcome Rate of symptomatic coronavirus disease 2019 by 6 months 14.7 % 14.7 12.3 11.0 % https://web.pathway.md/studies/rechMV4WEHzjC7knQ 1/2 6/27/23, 11:46 PM BRACE Pathway 7.3 % 3.7 % No significant difference 0.0 % BCG vaccine Placebo No significant difference in the rate of symptomatic COVID-19 by 6 months (14.7% vs. 12.3%; AD 2.4%, 95% CI -0.7 to 5.5) Secondary outcomes No significant difference in the rate of risk of severe COVID-19 by 6 months (7.6% vs. 6.5%; AD 1.1%, 95% CI -1.2 to 3.5) No significant difference in symptomatic or severe COVID-19 (7.9% vs. 6.4%; HR 1.23, 95% CI 0.96 to 1.59) No significant difference in pneumonia due to COVID-19 (0.4% vs. 0.4%; HR 0.93, 95% CI 0.32 to 2.64) Safety outcomes No significant difference in serious adverse events. Conclusion In healthcare workers, BCG vaccine was not superior to placebo with respect to the rate of symptomatic COVID-19 by 6 months. Reference Laure F Pittet, Nicole L Messina, Francesca Orsini et al. Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers. N Engl J Med. 2023 Apr 27;388(17):1582- 1596. Open reference URL https://web.pathway.md/studies/rechMV4WEHzjC7knQ 2/2
6/27/23, 11:47 PM BRASS Pathway Feedback Search Clinical Topics Home Studies BRASS BRASS Disease Disease Raynaud's phenomenon Systemic sclerosis Trial question What is the role of botulinum toxin in patients with systemic sclerosis-associated Raynaud's phenomenon? Study design Multi-center Double blinded RCT Population Characteristics of study participants 80.0% female N = 90 20.0% male 90 patients (72 female, 18 male) Inclusion criteria: adult patients with systemic sclerosis-associated Raynaud's phenomenon Key exclusion criteria: history of myasthenia gravis or Eaton Lambert syndrome; active infection in either hand; inflammatory myositis < 2 years or pre-existing motor neurone disease or upper limb motor neuropathy Interventions N=46 botulinum toxin (50 unit of botox injection into the palms of both hands) N=44 placebo (matching placebo injection into the palms of both hands) Primary outcome Reduction in median number of daily Raynaud's phenomenon attacks at 4 weeks postinjection 1.0/d 1 1 0 8/d https://web.pathway.md/studies/recW2DSmavja7Uy5Q 1/2 6/27/23, 11:47 PM BRASS Pathway 0.8/d 0.5/d 0.3/d No significant difference 0.0/d Botulinum toxin Placebo No significant difference in reduction in the median number of daily Raynaud's phenomenon attacks at 4 weeks postinjection (1 episode/day vs. 1 episode/day; RR 1, 95% CI -5.34 to 7.34) Safety outcomes No significant differences in pain during injections, Raynaud's Condition Score, Quality of Life, Hand function. Significant difference in transient hand muscle weakness (35% vs. 5%). Conclusion In adult patients with systemic sclerosis-associated Raynaud's phenomenon, botulinum toxin was not superior to placebo with respect to reduction in the median number of daily Raynaud's phenomenon attacks at 4 weeks postinjection. Reference Patricia Senet, Herv Maillard, Elisabeth Diot et al. Efficacy and Safety of Botulinum Toxin in Adults with Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol. 2023 Mar;75(3):459- 467. Open reference URL https://web.pathway.md/studies/recW2DSmavja7Uy5Q 2/2
6/27/23, 11:49 PM Breast cancer recurrence Pathway Feedback Search Clinical Topics Home Studies Breast cancer recurrence Breast cancer recurrence Trial question What is the role of regional anesthesia-analgesia in breast cancer recurrence after potentially curative surgery? Study design Multi-center Open label RCT Population 2132 female patients Inclusion criteria: women aged < 85 years having potentially curative primary breast cancer resections Key exclusion criteria: previous surgery for breast cancer (except diagnostic biopsies), inflammatory breast cancer, scheduled free-flap reconstruction, contraindications to either anesthetic approach or analgesic, or other cancer not in long-term remission Interventions N=1043 regional anesthesia-analgesia (paravertebral blocks and propofol) N=1065 general anesthesia (sevoflurane and opioid analgesia) Primary outcome Local or metastatic breast cancer recurrence 10.0 % 10 10 7.5 % 5.0 % 2.5 % No significant difference 0.0 % Regional anesthesia-analgesia General anesthesia No significant difference in local or metastatic breast cancer recurrence (10% vs. 10%; HR 0.97, 95% CI 0.74 to 1.28) Secondary outcomes No significant difference in incisional pain at 6 months and 12 months (52% vs. 52%; aOR 1, 95% CI 0.85 to 1.17) Safety outcomes https://web.pathway.md/studies/recWdCHyDexCO3Ztz 1/2 6/27/23, 11:49 PM Breast cancer recurrence Pathway y No significant differences in quality of life as assessed by scores on SF-12, death. Significant difference in postoperative nausea (8% vs. 20%). Conclusion In women aged < 85 years having potentially curative primary breast cancer resections, regional anesthesia-analgesia was not superior to general anesthesia with respect to local or metastatic breast cancer recurrence. Reference Daniel I Sessler, Lijian Pei, Yuguang Huang et al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet. 2019 Nov 16;394(10211):1807-1815. Open reference URL https://web.pathway.md/studies/recWdCHyDexCO3Ztz 2/2
6/27/23, 11:47 PM BREATHE Pathway Feedback Search Clinical Topics Home Studies BREATHE BREATHE Trial question What is the effect of protocolized weaning with early extubation to noninvasive ventilation on time to liberation from mechanical ventilation among patients with respiratory failure? Study design Multi-center Open label RCT Population Characteristics of study participants 49.0% female N = 364 51.0% male 364 patients (180 female, 184 male) Inclusion criteria: adult patients who received invasive mechanical ventilation > 48 hours and in whom a spontaneous breathing trial failed Key exclusion criteria: presence of a tracheostomy, contraindications to noninvasive ventilation, profound neurological deficit, home ventilation prior to admission, need for further surgery or sedation Interventions N=182 noninvasive weaning (extubation and immediate noninvasive ventilation via face mask) N=182 invasive weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) Primary outcome Time to successful liberation from mechanical ventilation among survivors 4.5 days 4.5 4.3 3.4 days 2.3 days 1.1 days No significant difference 0.0 days https://web.pathway.md/studies/recI9srtUTdjmypJX 1/2 6/27/23, 11:47 PM BREATHE Pathway y Noninvasive weaning Invasive weaning No significant difference in time to successful liberation from mechanical ventilation among survivors (4.3 days vs. 4.5 days; aHR 0.91, 95% CI 0.71 to 1.12) Secondary outcomes Borderline significant decrease in duration of invasive ventilation (1 day vs. 4 day; IRR 0.6, 95% CI 0.47 to 0.87) Borderline significant decrease in ventilator days (3 days vs. 4 days; IRR 0.8, 95% CI 0.62 to 1) No significant difference in tracheostomy (23.6% vs. 30.2%; OR 0.7, 95% CI 0.44 to 1.15) Safety outcomes No significant differences in adverse events, death before ICU discharge. Significant difference in antibiotics for presumed respiratory infection (60.4% vs. 70.3%). Conclusion In adult patients who received invasive mechanical ventilation > 48 hours and in whom a spontaneous breathing trial failed, noninvasive weaning was not superior to invasive weaning with respect to time to successful liberation from mechanical ventilation among survivors. Reference Gavin D Perkins, Dipesh Mistry, Simon Gates et al. Effect of Protocolized Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe Randomized Clinical Trial. JAMA. 2018 Nov 13;320(18):1881-1888. Open reference URL https://web.pathway.md/studies/recI9srtUTdjmypJX 2/2
6/27/23, 11:47 PM BRIDGE Pathway Feedback Search Clinical Topics Home Studies BRIDGE BRIDGE Disease Disease Disease Atrial fibrillation Deep vein thrombosis Periope Trial question Is forgoing bridging anticoagulation noninferior to perioperative bridging in patients with AF? Study design Multi-center Double blinded RCT Population Characteristics of study participants 27.0% female N = 1884 73.0% male 1884 patients (502 female, 1382 male) Inclusion criteria: patients with AF who need an interruption in warfarin treatment (5 days before the procedure) for an elective operation or other elective invasive procedure Key exclusion criteria: a mechanical heart valve; stroke, systemic embolism, or TIA within the previous 12 weeks; major bleeding within the previous 6 weeks; CrCl of < 30 mL/min; platelet count of < 100 10 /L, or planned cardiac, intracranial, or intraspinal surgery Interventions N=950 avoiding routine bridging (matching subcutaneous placebo BID) N=934 routine bridging therapy (100 IU dalteparin per kg of body weight administered SC BID from 3 days before the procedure until 24h before the procedure and then 5-10 days after the procedure) Primary outcome Arterial thromboembolism at 30 days after procedure https://web.pathway.md/studies/recTu4e1v8XGU8dTt 1/2 6/27/23, 11:47 PM BRIDGE Pathway 0.4 % 0.4 0.3 % 0.3 0.2 % Difference not exceeding nonferiority margin 0.1 % 0.0 % Avoiding routine bridging Routine bridging therapy Difference not exceeding nonferiority margin in arterial thromboembolism at 30 days after the procedure (0.4% vs. 0.3%; AD 0.1%, 95% CI -0.6 to 0.8) Secondary outcomes No significant difference in death (0.5% vs. 0.4%; AD 0.1%, 95% CI -1.1 to 1.3) No significant difference in myocardial infarction (0.8% vs. 1.6%; ARD -0.8, 95% CI -1.75 to 0.15) No significant difference in deep vein thrombosis (ARD -0.1, 95% CI -0.27 to 0.07) Safety outcomes Significant differences in major bleeding (1.3% vs. 3.2%), minor bleeding (12.0% vs. 20.9%). Conclusion In patients with AF who need an interruption in warfarin treatment (5 days before the procedure) for an elective operation or other elective invasive procedure, avoiding routine bridging was noninferior to routine bridging therapy with respect to arterial thromboembolism at 30 days after the procedure. Reference Douketis JD, Spyropoulos AC, Kaatz S et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015 Aug 27;373(9):823-33. Open reference URL https://web.pathway.md/studies/recTu4e1v8XGU8dTt 2/2
6/27/23, 11:49 PM BrigHTN (baxdrostat 0.5 mg) Pathway Feedback Search Clinical Topics Home Studies BrigHTN (baxdrostat 0.5 mg) BrigHTN (baxdrostat 0.5 mg) Disease Hypertension Trial question What is the role of low-dose baxdrostat in patients with treatment-resistant hypertension? Study design Multi-center Double blinded RCT Population Characteristics of study participants 43.0% female N = 138 57.0% male 138 patients (60 female, 78 male) Inclusion criteria: patients who had treatment-resistant hypertension, with BP 130/80 mmHg, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic Key exclusion criteria: mean seated systolic BP of at least 180 mmHg or diastolic BP of at least 110 mmHg; an eGFR of < 45 mL/min/1.73 m ; uncontrolled diabetes Interventions N=69 baxdrostat (at a dose of 0.5 mg daily for 12 weeks) N=69 placebo (matching placebo for 12 weeks) Primary outcome Reduction in mean systolic blood pressure at week 12 12.1 12.1 mmHg 9 4 https://web.pathway.md/studies/rec0VuNRDG6vsqvae 1/2 6/27/23, 11:49 PM BrigHTN (baxdrostat 0.5 mg) Pathway 9.4 9.1 mmHg 6.0 mmHg 3.0 mmHg No significant difference 0.0 mmHg Baxdrostat Placebo No significant difference in reduction in mean systolic BP at week 12 (12.1 mmHg vs. 9.4 mmHg; AD 2.7 mmHg, 95% CI 0 to 5.4) Secondary outcomes No significant difference in reduction in diastolic BP at week 12 (8.6 mmHg vs. 9.2 mmHg; AD -0.6 mmHg, 95% CI -1.2 to 0) No significant difference in reduction in urinary aldosterone levels at 24 hours (187 ng/g vs. -6 ng/g; AD 181 ng/g, 95% CI -0.31 to 362.31) Safety outcomes No significant difference in adverse events. Conclusion In patients who had treatment-resistant hypertension, with BP 130/80 mmHg, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, baxdrostat was not superior to placebo with respect to reduction in mean systolic BP at week 12. Reference Mason W Freeman, Yuan-Di Halvorsen, William Marshall et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med. 2023 Feb 2;388(5):395-405. Open reference URL https://web.pathway.md/studies/rec0VuNRDG6vsqvae 2/2
6/27/23, 11:49 PM BrigHTN (baxdrostat 1 mg) Pathway Feedback Search Clinical Topics Home Studies BrigHTN (baxdrostat 1 mg) BrigHTN (baxdrostat 1 mg) Disease Hypertension Trial question What is the role of mid-dose baxdrostat in patients with treatment-resistant hypertension? Study design Multi-center Double blinded RCT Population Characteristics of study participants 43.0% female N = 139 57.0% male 139 patients (60 female, 79 male) Inclusion criteria: patients who had treatment-resistant hypertension, with BP 130/80 mmHg, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic Key exclusion criteria: mean seated systolic BP of at least 180 mmHg or diastolic BP of at least 110 mmHg; an eGFR of < 45 mL/min/1.73 m ; uncontrolled diabetes Interventions N=70 baxdrostat (at a dose of 1 mg daily for 12 weeks) N=69 placebo (matching placebo for 12 weeks) Primary outcome Reduction in mean systolic blood pressure at week 12 17.5 mmHg 17.5 https://web.pathway.md/studies/recPwhVPcTBp2dPnA 1/2 6/27/23, 11:49 PM BrigHTN (baxdrostat 1 mg) Pathway 13.1 mmHg 9.4 8.8 mmHg 4.4 mmHg Significant increase 0.0 mmHg Baxdrostat Placebo Significant increase in reduction in mean systolic BP at week 12 (17.5 mmHg vs. 9.4 mmHg; AD 8.1 mmHg, 95% CI 2.8 to 13.5) Safety outcomes No significant difference in adverse events. Conclusion In patients who had treatment-resistant hypertension, with BP 130/80 mmHg, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, baxdrostat was superior to placebo with respect to reduction in mean systolic BP at week 12. Reference Mason W Freeman, Yuan-Di Halvorsen, William Marshall et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med. 2023 Feb 2;388(5):395-405. Open reference URL https://web.pathway.md/studies/recPwhVPcTBp2dPnA 2/2
6/27/23, 11:49 PM BrigHTN (baxdrostat 2 mg) Pathway Feedback Search Clinical Topics Home Studies BrigHTN (baxdrostat 2 mg) BrigHTN (baxdrostat 2 mg) Disease Hypertension Trial question What is the role of high-dose baxdrostat in patients with treatment-resistant hypertension? Study design Multi-center Double blinded RCT Population Characteristics of study participants 41.0% female N = 136 59.0% male 136 patients (56 female, 80 male) Inclusion criteria: patients who had treatment-resistant hypertension, with BP 130/80 mmHg, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic Key exclusion criteria: mean seated systolic BP of at least 180 mmHg or diastolic BP of at least 110 mmHg; an eGFR of < 45 mL/min/1.73 m ; uncontrolled diabetes Interventions N=67 baxdrostat (at a dose of 2 mg daily for 12 weeks) N=69 placebo (matching placebo for 12 weeks) Primary outcome Reduction in systolic blood pressure at week 12 20.3 mmHg 20.3 https://web.pathway.md/studies/rec67ZBEe4bP5GO2i 1/2 6/27/23, 11:49 PM BrigHTN (baxdrostat 2 mg) Pathway 15.2 mmHg 10.2 mmHg 9.4 5.1 mmHg Significant increase 0.0 mmHg Baxdrostat Placebo Significant increase in reduction in systolic BP at week 12 (20.3 mmHg vs. 9.4 mmHg; AD 11 mmHg, 95% CI 5.5 to 16.4) Secondary outcomes Significant increase in reduction in diastolic BP at week 12 (14.3 mmHg vs. 9.2 mmHg; AD 5.2 mmHg, 95% CI 1.6 to 8.7) Safety outcomes No significant difference in adverse events. Conclusion In patients who had treatment-resistant hypertension, with BP 130/80 mmHg, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, baxdrostat was superior to placebo with respect to reduction in systolic BP at week 12. Reference Mason W Freeman, Yuan-Di Halvorsen, William Marshall et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med. 2023 Feb 2;388(5):395-405. Open reference URL https://web.pathway.md/studies/rec67ZBEe4bP5GO2i 2/2
6/27/23, 11:47 PM BRIM-3 Pathway Feedback Search Clinical Topics Home Studies BRIM 3 BRIM 3 Disease Cutaneous melanoma Trial question What is the effect of vemurafenib in patients with metastatic melanoma with the BRAF V600E mutation? Study design Multi-center Open label RCT Population Characteristics of study participants 44.0% female N = 675 56.0% male 675 patients (294 female, 381 male) Inclusion criteria: patients with previously untreated, metastatic melanoma with the BRAF V600E mutation Key exclusion criteria: history of cancer within the past 5 years or metastases to the CNS, unless such metastases had been definitively treated > 3 months previously with no progression and no requirement for continued corticosteroid therapy, and concomitant treatment with any other anticancer therapy Interventions N=337 vemurafenib (at a dose of 960 mg BID PO) N=338 dacarbazine (at a dose of 1,000 mg per square meter of body-surface area by intravenous infusion every 3 weeks) Primary outcome https://web.pathway.md/studies/recpmoXwPeCWJw5Ke 1/2 6/27/23, 11:47 PM BRIM-3 Pathway Progression-free survival 5.3 months 5.3 4.0 months 2.6 months 1.6 1.3 months Significant decrease 0.0 months Vemurafenib Dacarbazine Significant decrease in progression-free survival (5.3 months vs. 1.6 months; HR 0.26, 95% CI 0.2 to 0.33) Secondary outcomes Significant increase in response rate (48% vs. 5%; AD 43%, 95% CI 17.49 to 68.51) Safety outcomes No significant difference in fatigue and vomiting. Significant differences in adverse events leading to dose modification/interruption (38% vs. 16%), arthralgia (21% vs. 1%), rash (18% vs. 0%), SCC (12% vs. < 1%), keratoacanthoma (8% vs. 0%), and alopecia (8% vs. 0%). Conclusion In patients with previously untreated, metastatic melanoma with the BRAF V600E mutation, vemurafenib was superior to dacarbazine with respect to a progression-free survival. Reference Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16. Open reference URL https://web.pathway.md/studies/recpmoXwPeCWJw5Ke 2/2
6/27/23, 11:48 PM BUCKLED Pathway Feedback Search Clinical Topics Home Studies BUCKLED BUCKLED Disease Distal radius fracture Trial question Is ultrasonography noninferior to radiography as initial diagnostic imaging method in children and adolescents with distal forearm injury? Study design Multi-center Open label RCT Population Characteristics of study participants 47.0% female N = 270 53.0% male 270 patients (126 female, 144 male) Inclusion criteria: participants 5-15 years of age who presented to the emergency department with an isolated distal forearm injury, without a clinically visible deformity, in whom further evaluation with imaging was indicated Key exclusion criteria: injury sustained for > 48 hours at time of emergency department presentation; known metabolic bone disease; suspicion of non-accidental injury; congenital bone malformation; compound fracture Interventions N=135 ultrasonography (point-of-care ultrasonography performed by emergency department healthcare practitioner) N=135 radiography (biplanar imaging performed by a radiographer and later reported by a radiologist) P i t https://web.pathway.md/studies/recOF7dwUXGrLcXTF 1/2 6/27/23, 11:48 PM BUCKLED Pathway Primary outcome Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System score at 4 weeks 36.4 36.4 36.3 27.3 18.2 Difference not exceeding nonferiority margin 9.1 0.0 Ultrasonography Radiography Difference not exceeding nonferiority margin in PROMIS System score at 4 weeks (36.4 vs. 36.3; MD 0.1, 95% CI -1.3 to 1.4) Secondary outcomes No significant difference in PROMIS System score at 1 week (28.4 vs. 27.7; MD 0.7, 95% CI -1.4 to 2.8) No significant difference in PROMIS System score at 8 weeks (39.2 vs. 39.1; MD 0.1, 95% CI -0.5 to 0.7) No significant difference in participant-reported satisfaction at week 4 (1.57 vs. 1.72; MD -0.15, 95% CI -0.36 to 0.06) Safety outcomes No significant difference in adverse events or unplanned returns to the emergency department. Conclusion In participants 5-15 years of age who presented to the emergency department with an isolated distal forearm injury, without a clinically visible deformity, in whom further evaluation with imaging was indicated, ultrasonography was noninferior to radiography with respect to PROMIS System score at 4 weeks. Reference Peter J Snelling, Philip Jones, David Bade et al. Ultrasonography or Radiography for Suspected Pediatric Distal Forearm Fractures. N Engl J Med. 2023 Jun 1;388(22):2049-2057. Open reference URL https://web.pathway.md/studies/recOF7dwUXGrLcXTF 2/2
6/28/23, 12:01 AM C/SOAP Pathway Feedback Search Clinical Topics Home Studies C/SOAP C/SOAP Disease Cesarean delivery Trial question What is the role of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective Cesarean delivery? Study design Multi-center Double blinded RCT Population 2013 female patients Inclusion criteria: women with a singleton pregnancy with a gestation of 24 weeks who were undergoing Cesarean delivery during labor or after membrane rupture Key exclusion criteria: known allergy to azithromycin; subsequent vaginal delivery; azithromycin use within 7 days before randomization; chorioamnionitis; fetal death or major congenital anomaly Interventions N=1019 azithromycin (500 mg intravenous azithromycin plus standard antibiotic prophylaxis) N=994 placebo (saline-based matching placebo plus standard antibiotic prophylaxis) Primary outcome Rate of composite of endometriosis, wound infection, or other infection occurring within 6 weeks 12.0 % 12 9.0 % 6.1 6.0 % Significant decrease 3.0 % NNT = 17 0.0 % https://web.pathway.md/studies/recWunbVG7QIU03R1 1/2 6/28/23, 12:01 AM C/SOAP Pathway Azithromycin Placebo Significant decrease in the rate of composite of endometriosis, wound infection, or other infection occurring within 6 weeks (6.1% vs. 12%; RR 0.51, 95% CI 0.38 to 0.68) Secondary outcomes No significant difference in neonatal death or complications (14.3% vs. 13.6%; RR 1.05, 95% CI 0.85 to 1.31) Significant decrease in postpartum fever (5% vs. 8.1%; RR 0.61, 95% CI 0.44 to 0.86) Significant decrease in postpartum readmission or unscheduled visit (8.1% vs. 12.4%; RR 0.66, 95% CI 0.51 to 0.86) Safety outcomes No significant difference in neonatal serious adverse events. Significant difference in maternal serious adverse events (1.5% vs. 2.9%). Conclusion In women with a singleton pregnancy with a gestation of 24 weeks who were undergoing Cesarean delivery during labor or after membrane rupture, azithromycin was superior to placebo with respect to the rate of composite of endometriosis, wound infection, or other infection occurring within 6 weeks. Reference Alan T N Tita, Jeff M Szychowski, Kim Boggess et al. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. N Engl J Med. 2016 Sep 29;375(13):1231-41. Open reference URL https://web.pathway.md/studies/recWunbVG7QIU03R1 2/2
6/28/23, 12:01 AM CADISS Pathway Feedback Search Clinical Topics Home Studies CADISS CADISS Disease Cervical artery dissection Trial question What is the effect of antiplatelet therapy in patients with extracranial carotid and vertebral artery dissection? Study design Multi-center Open label RCT Population Characteristics of study participants 30.0% female N = 250 70.0% male 250 patients (76 female, 174 male) Inclusion criteria: patients with extracranial carotid and vertebral dissection with onset of symptoms within the past 7 days Key exclusion criteria: intracranial cerebral artery dissection; contraindications to either antiplatelet or anticoagulation drugs, including active peptic ulceration or bleeding peptic ulcer within 1 year; use of antiplatelet or anticoagulants drugs for other reasons (eg, prosthetic heart valves); and pregnancy Interventions N=126 antiplatelet treatment (aspirin, dipyridamole, or clopidogrel alone or in combination, aiming for an INR of 2-3) N=124 anticoagulant treatment (heparin (either UFH or a therapeutic dose of low-molecular- weight heparin) followed by warfarin, aiming for an INR of 2-3) P i t https://web.pathway.md/studies/recyN370P831uOmdz 1/2 6/28/23, 12:01 AM CADISS Pathway Primary outcome Ipsilateral stroke or death at 3 months, in intention-to-treat population 2.0 % 2 1.5 % 1.0 % 1 0.5 % No significant difference 0.0 % Antiplatelet treatment Anticoagulant treatment No significant difference in ipsilateral stroke or death at 3 months, in the intention-to-treat population (2% vs. 1%; OR 0.335, 95% CI 0.01 to 4.23) Secondary outcomes No significant difference in stroke, major bleeding, or death (3% vs. 2%; OR 0.673, 95% CI 0.06 to 5.98) Safety outcomes No significant differences in adverse events, including major bleeding (0% vs. 1%). Conclusion In patients with extracranial carotid and vertebral dissection with onset of symptoms within the past 7 days, antiplatelet treatment was not superior to anticoagulant treatment with respect to ipsilateral stroke or death at 3 months, in the intention-to-treat population. Reference CADISS trial investigators, Markus HS, Hayter E et al. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol. 2015 Apr;14(4):361-7. Open reference URL https://web.pathway.md/studies/recyN370P831uOmdz 2/2
6/28/23, 12:01 AM CALISTO Pathway Feedback Search Clinical Topics Home Studies CALISTO CALISTO Disease Deep vein thrombosis Trial question What is the effect of fondaparinux in patients with acute, symptomatic superficial vein thrombosis of the legs? Study design Multi-center Double blinded RCT Population Characteristics of study participants 64.0% female N = 3002 36.0% male 3002 patients (1918 female, 1084 male) Inclusion criteria: patients with acute, symptomatic lower limb superficial vein thrombosis at least 5 cm long, as confirmed by standardized compression ultrasonography Key exclusion criteria: cancer treatment within the previous 6 months; symptomatic or asymptomatic deep vein thrombosis, symptomatic documented PE, or documented history of superficial vein thrombosis within the previous 3 months or deep vein thrombosis or PE within the previous 6 months Interventions N=1502 fondaparinux (subcutaneous dose of 2.5 mg daily for 45 days) N=1500 placebo (matching placebo of sodium chloride SC once daily for 45 days) Primary outcome https://web.pathway.md/studies/reczZ32xkbTcRgh5c 1/2 6/28/23, 12:01 AM CALISTO Pathway Death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to saphenofemoral junction or symptomatic recurrence of superficial vein thrombosis at day 47 5.9 % 5.9 4.4 % 3.0 % Significant decrease 1.5 % NNT = 20 0.9 0.0 % Fondaparinux Placebo Significant decrease in death from any cause or symptomatic PE, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial vein thrombosis at day 47 (0.9% vs. 5.9%; RR 0.15, 95% CI 0.08 to 0.26) Secondary outcomes Significant decrease in deep vein thrombosis or PE at 47 days (0.2% vs. 1.3%; RR 0.15, 95% CI 0.05 to 0.5) No significant difference in death at 47 days (0.1% vs. 0.1%; RR 1.99, 99% CI 0.18 to 21.87) Safety outcomes No significant differences in major bleeding (0.1% vs. 0.1%, p=1.00). Significant difference in serious adverse events (0.7% vs. 1.1%). Conclusion In patients with acute, symptomatic lower limb superficial vein thrombosis at least 5 cm long, as confirmed by standardized compression ultrasonography, fondaparinux was superior to placebo with respect to death from any cause or symptomatic PE, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial vein thrombosis at day 47. Reference Decousus H, Prandoni P, Mismetti P et al. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. N Engl J Med. 2010 Sep 23;363(13):1222-32. Open reference URL https://web.pathway.md/studies/reczZ32xkbTcRgh5c 2/2
6/28/23, 12:02 AM CAMERA Pathway Feedback Search Clinical Topics Home Studies CAMERA CAMERA Disease Rheumatoid arthritis Trial question What is the effect of intensive treatment with methotrexate in patients with early rheumatoid arthritis? Study design Multi-center Open label RCT Population Characteristics of study participants 67.0% female N = 299 33.0% male 299 patients (201 female, 98 male) Inclusion criteria: patients with early rheumatoid arthritis Key exclusion criteria: previous use of corticosteroids or any DMARD, use of cytotoxic or immunosuppressive drugs within a period of three months before inclusion, alcohol abuse (> 2 units per day), and psychological problems Interventions N=151 intensive methotrexate adjustment (tailored to the individual patient on the basis of predefined response criteria with monthly outpatient visits) N=148 conventional methotrexate adjustment (according to common practice, outpatient visit once every 3 months) Primary outcome Percentage of patients achieving at least one remission at 2 years https://web.pathway.md/studies/rectsU3AiQI6NUVRd 1/2 6/28/23, 12:02 AM CAMERA Pathway 50.0 % 50 37.5 % 37 25.0 % Significant increase 12.5 % NNT = 8 0.0 % Intensive methotrexate adjustment Conventional methotrexate adjustment Significant increase in the percentage of patients achieving at least one remission at 2 years (50% vs. 37%; RR 1.35, 95% CI 0.14 to 2.56) Secondary outcomes Significant decrease in time to remission (10.4 months vs. 14.3 months; ARD -3.9, 95% CI -6.21 to -1.59) Significant decrease in morning stiffness (17 vs. 23.7; MD -6.7, 95% CI -11.73 to -1.67) Significant decrease in tender joint count (3.6 vs. 5.5; MD -1.9, 95% CI -3.03 to -0.77) Safety outcomes No significant differences in adverse events, including gastrointestinal (24.6% vs. 25.2%), neurological disorders (18.8% vs. 18.8%), renal events (2.4% vs. 2.8%). Conclusion In patients with early rheumatoid arthritis, intensive methotrexate adjustment was superior to conventional methotrexate adjustment with respect to the percentage of patients achieving at least one remission at 2 years. Reference Verstappen SM, Jacobs JW, van der Veen MJ et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis. 2007 Nov;66(11):1443-9. Open reference URL https://web.pathway.md/studies/rectsU3AiQI6NUVRd 2/2
6/28/23, 12:02 AM CAMERA2 Pathway Feedback Search Clinical Topics Home Studies CAMERA2 CAMERA2 Disease Disease Disease Catheter-related bloodstream in Cellulitis Commu Trial question What is the role of combining antistaphylococcal -lactam and standard therapy in MRSA bacteremia? Study design Multi-center Open label RCT Population Characteristics of study participants 34.0% female N = 352 66.0% male 352 patients (121 female, 231 male) Inclusion criteria: hospitalized adults with MRSA bacteremia Key exclusion criteria: history of type 1 hypersensitivity reaction to -lactams; polymicrobial bacteremia; pregnancy; currently receiving -lactam therapy that could not be ceased or substituted for a non- -lactam antibiotic; death expected in the next 48 hours; treatment limitations precluding the use of antibiotics Interventions N=174 combination therapy (an antistaphylococcal -lactam [intravenous flucloxacillin, cloxacillin, or cefazolin] plus intravenous vancomycin or daptomycin) N=178 standard therapy (intravenous vancomycin or daptomycin) Primary outcome https://web.pathway.md/studies/rec6xfIbWNkELBpX0 1/2 6/28/23, 12:02 AM CAMERA2 Pathway Death, persistent bacteremia at day 5, microbiological relapse, or microbiological treatment failure at 90 days 39.0 % 39 35 29.3 % 19.5 % 9.8 % No significant difference 0.0 % Combination therapy Standard therapy No significant difference in death, persistent bacteremia at day 5, microbiological relapse, or microbiological treatment failure at 90 days (35% vs. 39%; AD -4.2%, 95% CI -14.3 to 6) Secondary outcomes No significant difference in death from all causes at 90 days (21% vs. 16%; AD 4.5%, 95% CI -3.7 to 12.7) Significant decrease in persistent bacteremia at day 5 (11% vs. 20%; AD -8.9%, 95% CI -16.6 to -1.2) Significant increase in AKI (excluding patients receiving dialysis at baseline) (23% vs. 6%; AD 17.2%, 95% CI 9.3 to 25.2) Safety outcomes No significant difference in microbiological treatment failure or microbiological relapse. Significant differences in adverse events (13.2% vs. 3.9%), AKI (7.5% vs. 0.6%). Conclusion In hospitalized adults with MRSA bacteremia, combination therapy was not superior to standard therapy with respect to death, persistent bacteremia at day 5, microbiological relapse, or microbiological treatment failure at 90 days. Reference Steven Y C Tong, David C Lye, Dafna Yahav et al. Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal -Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Feb 11;323(6):527-537. Open reference URL https://web.pathway.md/studies/rec6xfIbWNkELBpX0 2/2
6/28/23, 12:25 AM Can-SAD Pathway Feedback Search Clinical Topics Home Studies Can-SAD Can-SAD Disease Seasonal affective disorder Trial question What is the effect of light therapy in patients with winter seasonal affective disorder? Study design Multi-center Double blinded RCT Population Characteristics of study participants 67.0% female N = 96 33.0% male 96 patients (64 female, 32 male) Inclusion criteria: patients with winter seasonal affective disorder Key exclusion criteria: pregnancy, serious suicidal risk, DSM-IV criteria for organic mental disorders, substance use disorders within the last year, schizophrenia, paranoid or delusional disorders, other psychotic disorders, bipolar I disorder, panic disorder, or GAD not concurrent with major depressive episodes; serious unstable medical illness Interventions N=48 light therapy (10,000-lux light treatment and a placebo capsule for 8 weeks) N=48 fluoxetine (fluoxetine 20 mg/day and placebo light of 100-lux for 8 weeks) Primary outcome 24-item Hamilton Depression Scale score at week 1 22.2 22.2 20.7 16 6 https://web.pathway.md/studies/recgbXovpuJJl0mND 1/2 6/28/23, 12:25 AM Can-SAD Pathway 16.6 11.1 5.5 No significant difference 0.0 Light therapy Fluoxetine No significant difference in 24-item Hamilton Depression Scale score at week 1 (20.7 vs. 22.2; AD -1.5, 95% CI -3 to 0) Secondary outcomes No significant difference in clinical response (67% vs. 67%; RR 1, 95% CI -76794.23 to 76796.23) No significant difference in clinical remission (50% vs. 54%; RR 0.93, 95% CI -7.51 to 9.37) Safety outcomes No significant difference in treatment-emergent adverse event. Significant differences in agitation (0% vs. 12.5%), sleep disturbance (2.1% vs. 29.2%), and palpitations (0% vs. 10.4%). Conclusion In patients with winter seasonal affective disorder, light therapy was superior to fluoxetine with respect to a 24-item Hamilton Depression Scale score at week 1. Reference Lam RW, Levitt AJ, Levitan RD et al. The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Am J Psychiatry. 2006 May;163(5):805-12. Open reference URL https://web.pathway.md/studies/recgbXovpuJJl0mND 2/2
6/28/23, 12:25 AM Canadian National Breast Screening Study Pathway Feedback Search Clinical Topics Home Studies Canadian National Breast Screening Study Canadian National Breast Screening Study Trial question What is the role of annual mammography screening in women for breast cancer incidence? Study design Multi-center Open label RCT Population 89835 female patients Inclusion criteria: women aged 40-59 years with no history of breast cancer Key exclusion criteria: mammography in the previous 12 months; history of breast cancer; pregnancy Interventions N=44925 mammography (annual physical breast examinations) N=44910 no mammography (a single examination followed by usual care in the community) Primary outcome Deaths from breast cancer in follow-up period 1.1 % 1.12 1.11 0.8 % 0.6 % 0.3 % No significant difference 0.0 % Mammography No mammography No significant difference in deaths from breast cancer in the follow-up period (1.11% vs. 1.12%; HR 0.99, 99% CI 0.88 to 1.12) Secondary outcomes No significant difference in death from all causes in the follow-up period (10.66% vs. 10.44%; HR 1.02, 95% CI 0.98 to 1.06) Conclusion In women aged 40-59 years with no history of breast cancer, mammography was not superior to no mammography with respect to deaths from breast cancer in the follow-up period. https://web.pathway.md/studies/rectC1sjg3kuUflvg 1/2 6/28/23, 12:25 AM Canadian National Breast Screening Study Pathway Reference Anthony B Miller, Claus Wall, Cornelia J Baines et al. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014 Feb 11;348:g366. Open reference URL https://web.pathway.md/studies/rectC1sjg3kuUflvg 2/2