Methods | Multicentre, double‐blind, parallel‐group trial conducted in centres in Argentina and Brazil 2 treatment arms: OXC and PHT |
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Participants | Participants aged > 5 years with newly diagnosed epilepsy with partial seizures or generalised tonic‐clonic seizures A minimum of 2 seizures, separated by at least 48 h, within 6 months preceding trial entry No previous AED, except emergency treatment of seizures for a maximum of 3 weeks prior to trial entry Number randomised: OXC = 997, PHT = 94 100 male participants (52%); 143 of participants had partial epilepsy (74%) Mean age (range): 18.5 (5‐53) years |
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Interventions | Monotherapy with OXC or PHT 8‐week titration period started with 150 mg OXC or 50 mg PHT, increased bi‐weekly, based on clinical response to a regimen with daily doses of 450 mg‐2400 mg OXC or 150 mg‐800 mg PHT Continued during 48‐week maintenance with adjustment according to clinical response A third long‐term, open‐label extension phase followed the maintenance period. Double‐blind results only were reported Range of follow‐up: 1‐28 months |
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Outcomes | The proportion of seizure‐free participants who had at least 1 seizure during the maintenance period Time to premature discontinuation due to adverse experiences Rate of premature discontinuations for any reason Overall assessments of efficacy and tolerability and therapeutic effect Individual adverse experiences Laboratory values Seizure frequency during maintenance |
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Notes | IPD provided for all outcomes of this review by trial sponsor Novartis | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Treatment groups randomised in 1:1 ratio across centres via computer‐generated randomisation numbers over balanced blocks of size 6 |
Allocation concealment (selection bias) | Low risk | Allocation concealment was achieved with sequentially‐numbered packages which were identical and contained identical tablets (information provided by trial statistician) |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Trial conducted in 2 phases: 56‐week, double‐blind phase followed by long‐term, open‐label extension. Double‐blind phase results reported only Blind achieved with divisible OXC and PHT tablets identical in appearance |
Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not stated whether outcome assessor was blinded |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition rates reported in both treatment phases, participants withdrawing from treatment were no longer followed up so seizure outcomes had to be censored at time of withdrawal and therefore analyses for remission and seizure outcomes could not adopt an ITT approach |
Selective reporting (reporting bias) | Low risk | All outcomes reported or calculated with IPD provided (see footnote 2) |
Other bias | Low risk | None identified |