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Adjunctive pregabalin vs gabapentin for focal seizures

View Article: PubMed Central - PubMed

ABSTRACT

Objective:: To evaluate the comparative safety and adjunctive efficacy of pregabalin and gabapentin in reducing seizure frequency in patients with partial-onset seizures based on prestudy modeling showing superior efficacy for pregabalin.

Methods:: The design of this comparative efficacy and safety study of pregabalin and gabapentin as adjunctive treatment in adults with refractory partial-onset seizures was randomized, flexible dose, double blind, and parallel group. The study included a 6-week baseline and a 21-week treatment phase. The primary endpoint was the percentage change from baseline in 28-day seizure rate to the treatment phase.

Results:: A total of 484 patients were randomized to pregabalin (n = 242) or gabapentin (n = 242). Of these, 359 patients (187 pregabalin, 172 gabapentin) completed the treatment phase. The observed median and mean in percentage change from baseline was −58.65 and −47.7 (SD 48.3) for pregabalin and −57.43 and −45.28 (SD 60.6) for gabapentin. For the primary endpoint, there was no significant difference between treatments. The Hodges-Lehman estimated median difference was 0.0 (95% confidence interval −6.0 to 7.0). Safety profiles were comparable and consistent with prior trials.

Conclusions:: The absence of the anticipated efficacy difference based on modeling of prior, nearly identical trials and the larger-than-expected response rates of the 2 antiepileptic drugs were unexpected. These findings raise questions that are potentially important to consider in future comparative efficacy trials.

Clinicaltrials.gov identifier:: NCT00537940.

Classification of evidence:: This study provides Class II evidence that for patients with partial seizures enrolled in this study, pregabalin is not superior to gabapentin in reducing seizure frequency. Because of the atypical response rates, the results of this study are poorly generalizable to other epilepsy populations.

No MeSH data available.


CONSORT (Consolidated Standards of Reporting Trials) flow diagram of patient disposition and study populations
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Figure 2: CONSORT (Consolidated Standards of Reporting Trials) flow diagram of patient disposition and study populations

Mentions: Of 561 patients screened, 484 patients were randomized (pregabalin n = 242; gabapentin n = 242), 482 (pregabalin n = 241; gabapentin n = 241) were treated, and 359 (pregabalin n =187, gabapentin n = 172) completed the maintenance phase of the study (figure 2). Both groups had comparable baseline clinical and demographic characteristics (table 1). The most common concomitant AEDs are listed in table 1. During the 21-week double-blind phase of the study, the median doses of pregabalin and gabapentin were 450 and 1,500 mg/d, respectively. A few patients who on ESCI review were rediagnosed with generalized seizures but who had already been randomized (table 1) were allowed to complete the study and remained in the mITT population (i.e., the primary analysis). They were excluded from the per protocol analysis.


Adjunctive pregabalin vs gabapentin for focal seizures
CONSORT (Consolidated Standards of Reporting Trials) flow diagram of patient disposition and study populations
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035985&req=5

Figure 2: CONSORT (Consolidated Standards of Reporting Trials) flow diagram of patient disposition and study populations
Mentions: Of 561 patients screened, 484 patients were randomized (pregabalin n = 242; gabapentin n = 242), 482 (pregabalin n = 241; gabapentin n = 241) were treated, and 359 (pregabalin n =187, gabapentin n = 172) completed the maintenance phase of the study (figure 2). Both groups had comparable baseline clinical and demographic characteristics (table 1). The most common concomitant AEDs are listed in table 1. During the 21-week double-blind phase of the study, the median doses of pregabalin and gabapentin were 450 and 1,500 mg/d, respectively. A few patients who on ESCI review were rediagnosed with generalized seizures but who had already been randomized (table 1) were allowed to complete the study and remained in the mITT population (i.e., the primary analysis). They were excluded from the per protocol analysis.

View Article: PubMed Central - PubMed

ABSTRACT

Objective:: To evaluate the comparative safety and adjunctive efficacy of pregabalin and gabapentin in reducing seizure frequency in patients with partial-onset seizures based on prestudy modeling showing superior efficacy for pregabalin.

Methods:: The design of this comparative efficacy and safety study of pregabalin and gabapentin as adjunctive treatment in adults with refractory partial-onset seizures was randomized, flexible dose, double blind, and parallel group. The study included a 6-week baseline and a 21-week treatment phase. The primary endpoint was the percentage change from baseline in 28-day seizure rate to the treatment phase.

Results:: A total of 484 patients were randomized to pregabalin (n = 242) or gabapentin (n = 242). Of these, 359 patients (187 pregabalin, 172 gabapentin) completed the treatment phase. The observed median and mean in percentage change from baseline was −58.65 and −47.7 (SD 48.3) for pregabalin and −57.43 and −45.28 (SD 60.6) for gabapentin. For the primary endpoint, there was no significant difference between treatments. The Hodges-Lehman estimated median difference was 0.0 (95% confidence interval −6.0 to 7.0). Safety profiles were comparable and consistent with prior trials.

Conclusions:: The absence of the anticipated efficacy difference based on modeling of prior, nearly identical trials and the larger-than-expected response rates of the 2 antiepileptic drugs were unexpected. These findings raise questions that are potentially important to consider in future comparative efficacy trials.

Clinicaltrials.gov identifier:: NCT00537940.

Classification of evidence:: This study provides Class II evidence that for patients with partial seizures enrolled in this study, pregabalin is not superior to gabapentin in reducing seizure frequency. Because of the atypical response rates, the results of this study are poorly generalizable to other epilepsy populations.

No MeSH data available.