This multi-center clinical trial will test the hypothesis that the antiarrhythmic drug bidisomide is effective therapy for prophylaxis of symptomatic atrial fibrillation and paroxysmal supraventricular tachycardia. During the study, recurrences of symptomatic arrhythmias will be documented by using a transtelephonic electrocardiogram monitoring device to record and transmit an electrocardiogram. One thousand four hundred twenty (1420) patients who have qualifying arrhythmias will be randomized to one of three bidisomide doses (600 mg BID, 400 mg BID, 200 mg BID), or to placebo in a double-blind fashion; 568 patients will be assigned to placebo and 284 will be assigned to each of the three bidisomide doses. All patients will participate in the study for up to 52 weeks. For each patient, the tachycardia-free period will be measured from the time when steady-state plasma drug concentrations are expected until the first symptomatic recurrence of arrhythmia documented by the transtelephonic monitoring device. For each arrhythmia and each treatment group, the cumulative proportion of patients remaining free of symptomatic arrhythmias will be calculated using the Kaplan-Meier product-limit life table method. The efficacy of bidisomide in preventing recurrences of symptomatic arrhythmias will be tested statistically using the Cox proportional hazards model with a single (continuous) variable representing the dose of bidisomide. The study will detect, with high probability, a treatment effect that decreases the recurrence rate of symptomatic arrhythmias by a factor of two or more. The safety of bidisomide in patients with atrial fibrillation or flutter will be evaluated by assessing the effect of the two higher doses (600 mg BID and 400 mg BID) of bidisomide on total mortality. The sample size for the study is chosen to detect, with high probability, an adverse mortality effect equivalent to doubling of the mortality rate in the bidisomide treated patients over placebo. This study is important because there is a need to develop more effective antiarrhythmic therapies for supraventricular arrhythmias including atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia. Atrial fibrillation alone appears to affect almost 2,000,000 people in the United States; and hospitalization for atrial fibrillation is the leading cause of hospitalization for arrhythmias. Patients with atrial fibrillation have a five-fold increased risk of stroke and two-fold increased risk of cardiovascular mortality. This protocol was terminated prematurely on January 31, 1995 by the study executive committee due to the lack of therapeutic effect in any of the treatment groups.
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