American heart journal · 2002
Antiarrhythmic effects of azimilide in paroxysmal supraventricular tachycardia: efficacy and dose-response.
Клиническое исследованиеСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Page Richard L, Connolly Stuart J, Wilkinson William E, Marcello Stephen R, Schnell Daniel J, Pritchett Edward L C, Azimilide Supraventricular Arrhythmia Program (ASAP) Investigators
Аннотация
BACKGROUND: Azimilide is a novel classification III antiarrhythmic agent that blocks both I(Kr)and I(Ks)and shows evidence of efficacy in patients with atrial fibrillation or flutter. Its effect on paroxysmal supraventricular tachycardia (PSVT) has not been reported.
METHODS AND RESULTS: One hundred ninety-three patients with symptomatic PSVT were enrolled in 4 double-blind, randomized, placebo-controlled clinical trials with almost identical trial design (supraventricular arrhythmia-1 [SVA-1], SVA-2, SVA-3, and SVA-4), performed as a separate stratum of studies that also included a stratum of patients with atrial fibrillation or flutter. Patients received oral azimilide (100 mg in SVA-1 and SVA-3, 35 or 75 mg in SVA-2, and 125 mg in SVA-4) or matching placebo twice daily for 3 days (loading period), followed by once-daily dosing (maintenance period). The primary outcome variable was the first recording of a symptomatic supraventricular arrhythmia (either PSVT, atrial fibrillation, or atrial flutter) recorded on a transtelephonic electrocardiographic event recorder. The duration of study was 270 days in SVA-1 and SVA-2 and 180 days in SVA-3 and SVA-4. Combined analysis results of the PSVT stratum from the 4 studies showed a dose-response relationship in prolongation of time to recurrence (P =.02). In the combined 100-mg daily dose, the hazard ratio (placebo:azimilide) was 2.35 (P =.023). The hazard ratio for the 125-mg daily dose measured 1.28 (P = not significant). However, the time to recurrence was prolonged when the patients receiving 100 and 125 mg daily were combined and compared with placebo (P =.02). There were no deaths and 1 case of torsades de pointes.
CONCLUSION: These trial results suggest a significant dose-related suppression of PSVT with azimilide, with a low risk of serious adverse events.
METHODS AND RESULTS: One hundred ninety-three patients with symptomatic PSVT were enrolled in 4 double-blind, randomized, placebo-controlled clinical trials with almost identical trial design (supraventricular arrhythmia-1 [SVA-1], SVA-2, SVA-3, and SVA-4), performed as a separate stratum of studies that also included a stratum of patients with atrial fibrillation or flutter. Patients received oral azimilide (100 mg in SVA-1 and SVA-3, 35 or 75 mg in SVA-2, and 125 mg in SVA-4) or matching placebo twice daily for 3 days (loading period), followed by once-daily dosing (maintenance period). The primary outcome variable was the first recording of a symptomatic supraventricular arrhythmia (either PSVT, atrial fibrillation, or atrial flutter) recorded on a transtelephonic electrocardiographic event recorder. The duration of study was 270 days in SVA-1 and SVA-2 and 180 days in SVA-3 and SVA-4. Combined analysis results of the PSVT stratum from the 4 studies showed a dose-response relationship in prolongation of time to recurrence (P =.02). In the combined 100-mg daily dose, the hazard ratio (placebo:azimilide) was 2.35 (P =.023). The hazard ratio for the 125-mg daily dose measured 1.28 (P = not significant). However, the time to recurrence was prolonged when the patients receiving 100 and 125 mg daily were combined and compared with placebo (P =.02). There were no deaths and 1 case of torsades de pointes.
CONCLUSION: These trial results suggest a significant dose-related suppression of PSVT with azimilide, with a low risk of serious adverse events.