Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: a randomized double-blind clinical trial
Eugene Ramsay, Edward Faught, Allan Krumholz, Dean Naritoku, Michael Privitera, Lesley Schwarzman, Lian Mao, Frank Wiegand, Joseph Hulihan, CAPSS-272 Study Group, A Abubakr, R Armstrong, R Ayala, J Balmakund, R Beach, M Bensalem-Owen, V Biton, W Carlini, J Cavasos, G Connor, J DeCerce, A J Friedman, B V Gallo, R Gross, N Haddad, M Harris, R Hull, A Isa, P W Kaplan, P Klein, W A Knubley, D Labiner, K Liow, W A McElveen, C O'Donovan, E Passaro, E Pearlman, B Philbrook, K Rathke, W Rosenfeld, S Sahai-Srivastava, R Schwartz, J Slater, M Sperling, M Tabbaa, A B Thomas, T Ting, A Todorov, A Towne, B Vaughn, Eugene Ramsay, Edward Faught, Allan Krumholz, Dean Naritoku, Michael Privitera, Lesley Schwarzman, Lian Mao, Frank Wiegand, Joseph Hulihan, CAPSS-272 Study Group, A Abubakr, R Armstrong, R Ayala, J Balmakund, R Beach, M Bensalem-Owen, V Biton, W Carlini, J Cavasos, G Connor, J DeCerce, A J Friedman, B V Gallo, R Gross, N Haddad, M Harris, R Hull, A Isa, P W Kaplan, P Klein, W A Knubley, D Labiner, K Liow, W A McElveen, C O'Donovan, E Passaro, E Pearlman, B Philbrook, K Rathke, W Rosenfeld, S Sahai-Srivastava, R Schwartz, J Slater, M Sperling, M Tabbaa, A B Thomas, T Ting, A Todorov, A Towne, B Vaughn
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.
Trial registration: ClinicalTrials.gov NCT00210782.
Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.
Source: PubMed