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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.


Study design diagram
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Figure 1: Study design diagram

Mentions: This was a 2-arm, randomized, flexible-dose, double-blind, parallel-group, superiority study conducted in adult patients at 56 centers in Eastern and Western Europe, Asia, and South and Central America between February 2008 and July 2013 (EVENT: ClinicalTrials.gov NCT00537940). The study comprised 3 main phases: 6 weeks of baseline (screening), 9 weeks of double-blind dose escalation (titration), and 12 weeks of double-blind maintenance phase (21-week treatment phase) (figure 1). This design mirrored prior efficacy trials of both drugs, although to optimize safety and tolerability, there were 2 differences from prior trials. The first is that this study included 9 weeks of dose escalation compared to 0 to 4 weeks in earlier trials to potentially reduce discontinuations due to adverse events. Another difference is that uptitration was optional beyond a minimum dose of 100 mg 3 times daily (pregabalin) and 400 mg 3 times daily (gabapentin). After the 12-week double-blind maintenance phase, patients could enter a blinded continuation phase for a maximum of 2 years.9


Adjunctive pregabalin vs gabapentin for focal seizures
Study design diagram
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Study design diagram
Mentions: This was a 2-arm, randomized, flexible-dose, double-blind, parallel-group, superiority study conducted in adult patients at 56 centers in Eastern and Western Europe, Asia, and South and Central America between February 2008 and July 2013 (EVENT: ClinicalTrials.gov NCT00537940). The study comprised 3 main phases: 6 weeks of baseline (screening), 9 weeks of double-blind dose escalation (titration), and 12 weeks of double-blind maintenance phase (21-week treatment phase) (figure 1). This design mirrored prior efficacy trials of both drugs, although to optimize safety and tolerability, there were 2 differences from prior trials. The first is that this study included 9 weeks of dose escalation compared to 0 to 4 weeks in earlier trials to potentially reduce discontinuations due to adverse events. Another difference is that uptitration was optional beyond a minimum dose of 100 mg 3 times daily (pregabalin) and 400 mg 3 times daily (gabapentin). After the 12-week double-blind maintenance phase, patients could enter a blinded continuation phase for a maximum of 2 years.9

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.