A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.
In many countries oxcarbazepine (OXC) has been registered for use as first-line and add-on treatment for patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in children and adolescents with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 193 patients aged 5-18 years with either PS or GTCS were enrolled. After a retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase comprised two periods: an 8-week flexible titration period; followed by 48 weeks maintenance treatment. In the efficacy analyses, there were no statistically significant differences between OXC and PHT. Forty-nine (61%) patients in the OXC group and 46 (60%) in the PHT group were seizure-free during the maintenance period. In total, 24 patients in the OXC group discontinued treatment prematurely (two for tolerability reasons) compared with 34 in the PHT group (14 for tolerability reasons). The number of premature discontinuations due to adverse experiences was statistically significantly lower in the OXC group than in the PHT group. Moreover, the odds of an individual discontinuing prematurely (regardless of reason) were almost twice as high in the PHT group. This trial provides further support for the efficacy and safety of OXC as first-line treatment in children and adolescents with PS and GTCS. In addition, the results show that OXC in these patients has significant advantages over PHT in terms of tolerability and treatment retention. In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability. Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.
                SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.
                For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine.
                Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.
For participants with partial onset seizures oxcarbazepine is significantly less likely to be withdrawn, but current data do not allow a statement as to whether oxcarbazepine is equivalent, superior or inferior to phenytoin in terms of seizure control. However, the design of the studies may have biased seizure outcomes and misclassification of epilepsy type may have biased withdrawal rates.