title: Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: a randomized, double-blind, noninferiority trial.
abstract: To assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Zaccara
authors.forename: Mary
authors.initials: M
authors.lastname: Almas
authors.forename: Verne
authors.initials: V
authors.lastname: Pitman
authors.forename: Lloyd
authors.initials: L
authors.lastname: Knapp
authors.forename: Holly
authors.initials: H
authors.lastname: Posner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069583:Pregabalin; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D010889:Piracetam
keywords: Clinical trial; Levetiracetam; Noninferiority; Pregabalin; Seizure