THE AZIMILIDE POST-INFARCT SURVIVAL EVALUATION (ALIVE) TRIAL

The AzimiLide post-lnfarct surVival Evaluation (ALIVE) trial is a new clinical trial using an innovative design to examine the potential of azimilide, a novel type of antiarrhythmic, for improving survival in p ost myocardial infarction (MI) patients at high risk of sudden cardiac death. Azimilide is the first of a unique class of antiarrhythmic dru gs that blocks both slow and rapid components of the delayed rectifier potassium currents in human myocardium. Preclinical studies have show n the drug to be effective in reducing cardiac tachyarrhythmias, even under ischemic conditions. Currently, azimilide is in Phase III trials for the treatment of supraventricular arrhythmias. The ALIVE study de sign is based on lessons learned from the Cardiac Arrhythmia Suppressi on Trials (CAST), the Survival With Oral d-Sotalol (SWORD) trial, and the European Myocardial Infarction Amiodarone Trial (EMIAT) and identi fies recent post-MI patients at high risk of sudden cardiac death. The hypothesis underlying this trial is that azimilide will improve survi val in this patient population. The ALIVE trial is designed as a doubl e-blind, placebo-controlled, multinational trial that will overcome th e shortcomings of previous antiarrhythmic trials by using left ventric ular ejection fraction and heart rate variability as predictors to tar get a post-MI patient population at high risk of sudden death, The maj or inclusion criteria for the study are adult patients of either gende r with a left ventricular ejection fraction of 15-35% who have had a r ecent MI (within 6-21 days). Additional stratification will be based o n patients with heart rate variability less than or equal to 20 U (hea rt rate variability index). Exclusion criteria include factors that ma y predispose a patient to nonarrhythmia-induced death or to low risk o f sudden cardiac death caused by arrhythmia, Sample size is based on t he assumption that the all-cause mortality rate (the primary endpoint) for 1 year in placebo patients at high risk for sudden cardiac death (heart rate variability less than or equal to 20 U) is 15% and that az imilide will decrease all-cause mortality by at least 45% in these pat ients. The trial consists of 3 groups - patients receiving 75 mg azimi lide orally each day, patients receiving 100 mg azimilide orally each day, and patients receiving placebo. No dose adjustments for age, gend er, renal or hepatic failure, or concomitant use of warfarin or digoxi n are thought necessary with azimilide. Enrollment for the trial is ex pected to continue for 24 months, and treatment is scheduled to be adm inistered for a 1-year follow-up period. (C) 1998 by Excerpta Medica, Inc.