Methods | Randomised double-blind PCB-controlled parallel multicentre (71 in the USA and 5 in Canada) trial. 5 treatment arms: 1 PCB, 4 PGB. Patients randomised in blocks of 5, each allocated unique ID number. Capsule sizes varied (no further information available). Duration of baseline period: 8 weeks. There was no titration; 12-week treatment period | |
Participants | Patients 12 years and above (range 12 to 75 years, mean 38.4 years), 48.1% male, all with treatment-resistant partial epilepsy. Patients were on 1 to 4 baseline AEDs. 586 patients screened, 455 patients randomised: 100 patients to PCB (mean baseline seizure frequency: 22.3); 88 patients to 50 mg PGB (mean baseline seizure frequency: 27.4); 88 patients to 150 mg PGB (mean baseline 28-day seizure frequency: 23.1); 90 patients to 300 mg PGB (mean baseline 28-day seizure frequency: 19.1) and 89 patients to 600 mg PGB (mean baseline 28-day seizure frequency: 18.6) | |
Interventions | Group 1: PCB Group 2: 50 mg PGB daily Group 3: 150 mg PGB Group 4: 300 mg PGB Group 5: 600 mg PGB daily |
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Outcomes | Primary outcome: reduction in seizure frequency compared to baseline (response ratio) Secondary outcomes: responder rate, pairwise comparisons with PCB, adverse events |
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Notes | Blinding broken for interim analysis (data obtained were only known to committee who were not involved in further running of study) and for 1 patients who developed visual field defect. 2 patients were excluded from ITT analysis (1 withdrew consent, 1 had AEDs changed during baseline period). Seizure frequency and responder rate were calculated from data collected from seizure diaries and mean calculated over a 4-week period | |
Risk of bias | ||
Bias | Authors’ judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Used a computer-generated randomised schedule using block sizes of 5 |
Allocation concealment (selection bias) | Unclear risk | No information provided |
Blinding (performance bias and detection bias) All outcomes | Unclear risk | Study medication presented in identical capsules |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition rates reported. ITT analysis employed |
Selective reporting (reporting bias) | Unclear risk | All outcomes stated in methods section of paper were reported in the results; however, there was no protocol available to check a priori outcomes |
Other bias | High risk | Possibility of the inclusion of patients with primary generalised epilepsy Sponsored by same pharmaceutical company as with all the other included trials |