The azimilide post-infarct survival evaluation (ALIVE) trial

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Azimilide is a novel antiarrhythmic drug targeting potassium currents, showing preclinical efficacy against cardiac tachyarrhythmias.
• Previous trials like CAST, SWORD, and EMIAT highlighted the need for improved strategies in post-myocardial infarction (MI) patient survival.
• Identifying and treating post-MI patients at high risk for sudden cardiac death (SCD) remains a significant clinical challenge.

Purpose of the Study:

• To evaluate the efficacy of azimilide in reducing all-cause mortality in post-MI patients at high risk of SCD.
• To leverage lessons from prior antiarrhythmic trials to refine patient selection and study design.
• To investigate the potential of azimilide as a first-in-class antiarrhythmic agent for this vulnerable population.

Main Methods:

• The AzimiLide post-Infarct surVival Evaluation (ALIVE) is a double-blind, placebo-controlled, multinational Phase III trial.
• Inclusion criteria target adult patients with recent MI (6-21 days) and left ventricular ejection fraction (LVEF) of 15-35%, with stratification based on heart rate variability (HRV < or = 20 U).
• Patients are randomized into three groups: 75 mg azimilide daily, 100 mg azimilide daily, or placebo, with a 1-year follow-up period.

Main Results:

• The primary endpoint is 1-year all-cause mortality.
• Sample size calculations assume a 15% mortality rate in placebo patients with HRV < or = 20 U and hypothesize a 45% reduction with azimilide.
• The trial aims to enroll patients over 24 months.

Conclusions:

• The ALIVE trial hypothesizes that azimilide will improve survival in high-risk post-MI patients.
• The study design incorporates advanced risk stratification using LVEF and HRV to address limitations of previous trials.
• Findings will inform the role of azimilide in managing patients at risk of sudden cardiac death post-myocardial infarction.