BACKGROUND: Effective treatments for COVID-19 are urgently needed but conducting randomized trials during the pandemic has been challenging. METHODS: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3,500 outpatients and 2,500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine versus usual care, and aspirin versus usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine versus usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily versus usual care. The primary outcome for the colchicine randomization is need for high flow oxygen, mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization is major thrombotic events, need for high flow oxygen, mechanical ventilation, or death. RESULTS: At the completion of enrolment on February 10, 2022, the outpatient trial had enrolled 3,917 patients and the inpatient trial 2,754 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. CONCLUSIONS: The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials.
The Anti-Coronavirus Therapy (ACT) trials: design, baseline characteristics, and challenges.