Cardiac Arrhythmia Suppression Trial (CAST)

May 5, 2016 updated by: National Heart, Lung, and Blood Institute (NHLBI)
To determine whether drug treatment of asymptomatic ventricular arrhythmias in post-myocardial infarction patients reduced the incidence of sudden cardiac death and total mortality.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND:

Each year over 400,000 people in the United States die suddenly of coronary heart disease. The majority have known coronary heart disease. Of these, the post-myocardial infarction population constitutes a large proportion. About 8 to 15 percent of patients who recover from an acute myocardial infarction die in the subsequent year. Half of these deaths are usually sudden, presumably due to arrhythmia. Advanced age, poor ventricular function, and presence of ventricular arrhythmias can identify post-MI patients at high risk of sudden cardiac death and all-cause mortality.

A number of clinical trials have evaluated whether acute or chronic anti-arrhythmic drug therapy can reduce mortality in post-MI patients. Of these, only the use of acute intravenous and long-term beta-blockers, independently and in combination, had been shown to reduce mortality. However, beta-blockers have many actions in addition to being anti-arrhythmic agents and it is possible that these other effects may have been particularly important in prolonging life.

None of the clinical trials of other antiarrhythmic drugs had shown significant benefits from treatment, and a number had even failed to show a positive trend. It was certainly possible that treatment of ventricular premature depolarizations, in itself, did not lead to a reduction in mortality, or even sudden death. The studies that had been done, however, had not adequately addressed the issue. Most of the studies were small and did not select patients on the basis of frequent ectopic beats. Moreover, appropriate drugs in optimal doses may not have been used, and adverse effects may well have outweighed any potential benefit. Poor compliance, perhaps due to adverse effects, may also have limited the opportunity for a beneficial outcome.

In an effort to address some of these points, the National Heart, Lung, and Blood Institute initiated the Cardiac Arrhythmia Pilot Study in 1982. The objectives were to assess: whether post-MI patients with documented ventricular arrhythmia could be identified and enrolled into a double-blind clinical trial; whether one or more drugs could be found to effectively and safely reduce ventricular premature depolarizations over a one-year period; whether dose-adjustment could be carried out, using ambulatory ECG's; and whether good patient compliance could be maintained. The Cardiac Arrhythmia Pilot Study, which enrolled 500 patients, evaluated four active drugs (encainide, ethmozine, flecainide, imipramine) against placebo. The study was too small to determine whether any of these drugs had an effect on mortality or major morbidity. The study was completed in July 1986.

The pilot study demonstrated that patient recruitment was feasible, that dose-adjustment could be accomplished, and that good compliance to the protocol could be achieved. Because of the encouraging results of the pilot study, the NHLBI conducted a full-scale trial.

DESIGN NARRATIVE:

Randomized, double-blind. Enrollment began in June 1987 when twenty-seven clinical centers began to randomize 4,400 post-myocardial infarction patients to placebo or treatment with encainide, flecainide, or moricizine. Prior to actual randomization, there was an open-label titration period to identify patients who responded to treatment. A total of 1,727 patients who responded were randomized: 1,455 to encainide, flecainide, or placebo, and 272 to moricizine or placebo. In April 1989, encainide and flecainide were discontinued because of increased total mortality and sudden arrhythmic death. CAST continued to compare moricizine to placebo in 1,300 patients for 18 months until August 1991 when the moricizine portion of the trial was stopped early because of excess deaths. The primary outcome variable in the full-scale trial was sudden cardiac death, with total mortality a secondary endpoint. Data analysis continued through March 1998.

Study Type

Interventional

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Men and women with ventricular premature depolarization six days to two years after the start of myocardial infarction.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Alfred Hallstrom, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 1986

Study Completion

March 1, 1998

Study Registration Dates

First Submitted

October 27, 1999

First Submitted That Met QC Criteria

October 27, 1999

First Posted (Estimate)

October 28, 1999

Study Record Updates

Last Update Posted (Estimate)

May 6, 2016

Last Update Submitted That Met QC Criteria

May 5, 2016

Last Verified

August 1, 2004

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 45

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: CAST
    Information comments: NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.
  2. Study Protocol
  3. Study Forms

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myocardial Infarction

Clinical Trials on encainide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Latvia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe