Title of Trial
Azimilide Post-Infarction Survival Evaluation (ALIVE) trial

Date and Location of Presentation
The ALIVE Trial was presented on November 14, 2001, at the American Heart Association 74th Annual Scientific Sessions, in Anaheim, CA, USA.

Date and citation of primary publication(s) or References
Not Published

Purpose of the Trial
The purpose of this trial is to evaluate the effect of Azimilide on improving survival in post myocardial infarction patients at high risk of sudden cardiac death.

Study Category
Sudden Cardiac Death & Syncope

Patient Population
Adult patients with recent prior myocardial infarction

Inclusion Criteria

• Adult patient 18 to 75 years of age
• Myocardial infarction within 6 to 21 days
• Left ventricular ejection fraction of 15% to 35%

Exclusion Criteria

• History of Torsades de Pointes or other forms of polymorphic ventricular tachycardia
• Any history of ventricular tachycardia lasting > 10 beats, occurring > 48 hours after the myocardial infarction
• Class IV congestive heart failure
• Unstable angina
• Syncope or aborted sudden cardiac death
• Severe valvular disease
• Second or third degree atrioventricular block in the absence of a pacemaker
• Scheduled angioplasty or CABG
• Prior defibrillator implantation
• QTc > 450 ms
• History of stroke with residual neurological deficit
• Wolff-Parkinson-White syndrome
• Chronic liver disease or significant renal disease
• Serum potassium prior to randomization <4.0 or > 5.5 mEq/L
• Resting heart rate < 50 beats/minute
• Uncontrolled hypertension (>170/100 mm of Hg)
• History of organ toxicity related to amiodarone or on amiodarone within 1 month of enrollment
• Current use of any class I or III antiarrhythmic drugs
• Current use of any drugs that prolong the QT interval
• Participation in previous Azimilide trials
• Pregnancy
• Known alcohol or illicit drug abusers or carrying a diagnosis of psychosis
• Unwillingness to give informed consent

Study Design
Randomized, double-blinded, placebo-controlled, multinational trial of Azimilide versus placebo.

Primary Endpoints
One year all-cause mortality

Secondary Endpoints

• Arrhythmic, cardiac, non-cardiac mortality
• Effect of Azimilide on all-cause mortality in patients with single versus multiple prior myocardial infarctions
• Determine the effect of beta-blockers and Angiotensin converting enzype (ACE) inhibitors on all-cause mortality
• In-patient utilization pattern and cost of care
• Incidence of patient dropout

Baseline Characteristics
Patient number: 3,717
Mean Age: Not available
Gender: % female; 22%
Other characteristics: Patients were further stratified into a 'high-risk' subgroup if their measurement of heart rate variability was low (HRV<20 U).

Time to Follow-up
Up to 1 year

Results
There was no difference in all-cause mortality between Azimilide and placebo in both the high-risk group (hazard ratio [HR] =0.95, p=NS) and the entire at risk group (HR=1.0, p=NS).

Age, gender, class of heart failure, left ventricular ejection fraction, and diabetes made no difference to the subgroup endpoints.

Non-cardiac mortality was reduced with Azimilide but documented arrhythmia mortality was the same in both groups.

There were 5 (0.5%) episodes of non-fatal Torsades de Pointes in the Azimilide group versus 1 (0.1%) in the placebo group.

Fewer patients with baseline sinus rhythm at the beginning of the trial randomized to Azimilide developed atrial fibrillation during follow-up (HR=0.43, p=0.04)

Sponsor
Procter and Gamble Pharmaceuticals

Trial Status: Completed

Review written by Samir Saba, MD