Efficacy,tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new‐onset epilepsy: A randomized double‐blind clinical trial |
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Authors: | Eugene Ramsay Edward Faught Allan Krumholz Dean Naritoku Michael Privitera Lesley Schwarzman Lian Mao Frank Wiegand Joseph Hulihan for the CAPSS‐ Study Group |
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Affiliation: | 1. Epilepsy Institute, Ochsner Baptist Medical Center, New Orleans, Louisiana, U.S.A.;2. University of Alabama School of Medicine and Birmingham Veteran’s Affairs Medical Center, Birmingham, Alabama, U.S.A.;3. University of Maryland School of Medicine, Baltimore, Maryland, U.S.A.;4. Southern Illinois University, Springfield, Illinois, U.S.A.;5. Current address: University of South Alabama, Mobile, Alabama.;6. College of Medicine, University of Cincinnati, Cincinnati, Ohio, U.S.A.;7. Ortho‐McNeil Janssen Scientific Affairs, LLC, Titusville, New Jersey, U.S.A.;8. Current address: J&J Pharmaceutical Services LLC, Raritan, New Jersey. |
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Abstract: | Purpose: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new‐onset epilepsy. Methods: Randomized, double‐blind, 28‐day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new‐onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. Results: At day 28, the estimated seizure‐free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment‐related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). Conclusion: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new‐onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new‐onset epilepsy requiring rapid treatment initiation. |
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Keywords: | Complex partial seizures Epilepsy Generalized tonic‐clonic seizures Phenytoin Rapid‐initiation Topiramate |
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