Trinka 2013

Methods	Multi‐centre, open label, randomised, two parallel group stratified trial carried out in a community setting between February 2005 and October 2007 in 269 centres across 23 European countries and Australia. Four treatment arms: CBZ (controlled release), LEV (two arms) and VPS (extended release) ‐ see notes
Participants	Patients aged ≥16 years were included if they had two or more unprovoked seizures in the previous 2 years with at least one during the previous 6 months. Participants must not have received one of the trial drugs previously or treated for epilepsy with any other AED in the previous 6 months Number randomised (ITT population): CBZ = 503, LEV = 492 (CBZ branch), LEV = 349, VPS = 353 (VPS branch). 949 male participants (56%) 1048 participants with partial epilepsy (62%) Mean age (range): 40 (16 ‐ 89 years).
Interventions	Monotherapy with CBZ, LEV or VPS Titration over two weeks to target doses CBZ‐CR=600 mg/day, LEV=1000 mg/day, VPS‐ER=1000 mg/day, Range of follow up: 0 to 28.5 months
Outcomes	Time to withdrawal from trial medication (treatment withdrawal) after randomisation Time to first seizure after randomisation Treatment withdrawal rates at 6 and 12 months Seizure‐freedom rates at 6 and 12 months Change of baseline in quality of life measures (QOLIE‐31‐P and EQ‐5D) Treatment emergent adverse events (intensity and seriousness)
Notes	IPD provided for all outcomes of this review by trial sponsor UCB. Trial designed in 2 strata based on whether recommended treatment would be CBZ or VPS. Data analysed according to the separate strata in this review (see Data extraction and management)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation was stratified, no further information provided
Allocation concealment (selection bias)	Low risk	Treatment allocation was concealed by use of an interactive voice‐response system via telephone to manage the randomisation process
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label trial
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label trial
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rates reported, ITT approach, all randomised participants from the ITT population analysed from IPD provided (see footnote 2). 8 randomised participants excluded from ITT population due to no informed consent or lack of compliance with good clinical practice.
Selective reporting (reporting bias)	Low risk	All outcomes reported or calculated with IPD provided (see footnote 2)
Other bias	Low risk	None identified