Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: A randomized, double‐blind, noninferiority trial

Summary Objectives To assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures. Methods This was a randomized, double‐blind, flexible‐dose, parallel‐group noninferiority study of pregabalin and levetiracetam (randomized 1:1) as adjunctive treatment in adult patients with refractory partial seizures. The study included a 6‐week baseline phase, 4‐week dose‐escalation phase, and 12‐week maintenance phase. The primary endpoint was the proportion of patients with a ≥50% reduction in 28‐day seizure rate during the 12‐week maintenance phase, as compared with baseline. Noninferiority of pregabalin was declared if the lower limit of the 95% confidence interval ( CI ) for the difference in responder rates was greater than the prespecified noninferiority margin of −12%. A key secondary endpoint was the percent change from baseline in 28‐day seizure rate during the dose‐escalation and maintenance phases. Results Five hundred nine patients were randomized to pregabalin (n = 254) or levetiracetam (n = 255) and 418 (208 pregabalin, 210 levetiracetam) completed the maintenance phase. With both pregabalin and levetiracetam, the proportion of patients with a ≥50% reduction in 28‐day seizure rate was 0.59 (difference between groups [95% CI ], 0.00 [−0.08 to 0.09]). Because the lower bound of the 95% CI was greater than the prespecified noninferiority margin of −12%, pregabalin was not inferior to levetiracetam. There was no significant difference between pregabalin and levetiracetam in the percent change in 28‐day seizure rate (median difference [95% CI ], 4.1 [−2.6 to 10.9], p = 0.3571). In a post hoc analysis, the proportion of patients who were seizure‐free for the maintenance phase was lower with pregabalin (8.4%) than with levetiracetam (16.2%), p = 0.0155. Safety profiles were similar and consistent with prior trials. Significance These results indicate that pregabalin is noninferior, and has a similar tolerability, to levetiracetam as adjunctive therapy in reducing seizure frequency in patients with partial seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .