Azimilide post-infarct survival evaluation (ALIVE) trial

The Azimilide post-infarct 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 post myocardial infarction (MI) patients at high risk of sudden cardiac death. Azimilide is the first of a unique class of antiarrhythmic drugs that blocks both slow and rapid components of the delayed rectifier potassium currents in human myocardium. Preclinical studies have shown 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 design is based on lessons learned from the Cardiac Arrhythmia Suppression Trials (CAST), the Survival With Oral d- Sotalol (SWORD) trial, and the European Myocardial Infarction Amiodarone Trial (EMIAT) and identifies recent post-MI patients at high risk of sudden cardiac death. The hypothesis underlying this trial is that azimilide will improve survival in this patient population. The ALIVE trial is designed as a double-blind, placebo-controlled, multinational trial that will overcome the shortcomings of previous antiarrhythmic trials by using left ventricular ejection fraction and heart rate variability as predictors to target a post- MI patient population at high risk of sudden death. The major inclusion criteria for the study are adult patients of either gender with a left ventricular ejection fraction of 15-35% who have had a recent MI (within 6- 21 days). Additional stratification will be based on patients with heart rate variability ≤20 U (heart rate variability index). Exclusion criteria include factors that may predispose a patient to nonarrhythmia-induced death or to low risk of sudden cardiac death caused by arrhythmia. Sample size is based on the 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 ≤20 U) is 15% and that azimilide will decrease all-cause mortality by at least 45% in these patients. The trial consists of 3 groups - patients receiving 75 mg azimilide orally each day, patients receiving 100 mg azimilide orally each day, and patients receiving placebo. No dose adjustments for age, gender, renal or hepatic failure, or concomitant use of warfarin or digoxin are thought necessary with azimilide. Enrollment for the trial is expected to continue for 24 months, and treatment is scheduled to be administered far a 1-year follow-up period.