Antiarrhythmics Versus Implantable Defibrillators (AVID)

April 12, 2016 updated by: National Heart, Lung, and Blood Institute (NHLBI)
To evaluate if use of an implantable cardiac defibrillator (ICD) results in reduction in total mortality, when compared with conventional pharmacological therapy, in patients resuscitated from sudden cardiac death who are otherwise at very high risk of mortality from arrhythmic causes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND:

Sudden cardiac death is believed to account for a substantial proportion of deaths in patients with evidence of cardiovascular disease. The exact proportion of cardiac deaths that are classified as being sudden varies depending on the population, the underlying disease, and the definition of sudden death. Various estimates suggest that about 500,000 sudden cardiac deaths occur annually in the United States alone. The majority of sudden cardiac deaths are thought to be due to ventricular fibrillation (VF) or tachycardia (VT).

The commonest approach to preventing sudden cardiac death has been by the use of drugs that suppress ventricular ectopy. The rational for this approach is based upon an association between the presence or frequency of ventricular arrhythmia and subsequent mortality in several studies. None of the randomized controlled studies of numerous 'classical' antiarrhythmic agents (other than beta-blockers, which have only a modest effect on arrhythmia suppression) have demonstrated a reduction in sudden or non-sudden cardiac mortality. Indeed, in the recent Cardiac Arrhythmia Suppression Trial (CAST), two class Ic anti-arrhythmic agents demonstrated a 2.5 fold increase in the risk of sudden and non-sudden cardiac deaths despite excellent suppression of ventricular arrhythmia.

Given the disappointing results of most pharmacologic approaches to preventing sudden death, many investigators have turned to non-pharmacologic approaches such as surgery (endocardial resection, stellate ganglionectomy) or the implantation of devices that recognize VT or VF and deliver a shock. The greatest interest has been generated by work on the implantable cardiac defibrillator.

The study was reviewed by an ad hoc working group, the Clinical Applications and Prevention Advisory Committee, and several members of the Cardiology Advisory Committee prior to review and approval by the National Heart, Lung, and Blood Advisory Council in September 1991. The Request for Proposals was released in February 1992.

DESIGN NARRATIVE:

At approximately 28 clinical sites, patients with ventricular tachycardia or ventricular fibrillation were screened. Those with ventricular fibrillation or serious ventricular tachycardia were entered into a registry for long-term mortality follow-up using the National Death Index. Patients with the prospect of long-term benefit from an ICD and/or antiarrhythmic drug therapy and without exclusions to an ICD or to amiodarone and without a transient or correctible cause of the index event were entered into the trial.

Patients meeting the criteria were randomized to treatment with an ICD or treatment with antiarrhythmic drug therapy. Allocation was stratified by clinical site and index arrhythmia, either ventricular fibrillation or ventricular tachycardia. Patients assigned to the antiarrhythmic drug therapy and without contraindications to sotalol underwent subrandomization to either empiric amiodarone or sotalol, the latter treatment guided by either ambulatory monitoring or electrophysiologic testing. Patients who, after subrandomization, had low levels (less than 30 beats per hour) of ventricular ectopic beats and no inducible ventricular arrhythmias at electrophysiologic study were not treated with sotalol and instead received empiric amiodarone. The AVID protocol allowed usual clinical practice but restricted interventions to state-of-the art ICD devices and first-line antiarrhythmic agents to amiodarone and sotalol. Patients who could not take amiodarone were not included in the trial. The protocol encouraged the use of concurrent drugs such as angiotensin-converting enzyme inhibitors, aspirin, and beta-blockers when appropriate, administered before randomization and maintained throughout the study. The primary endpoint was total mortality. Secondary endpoints were cost of health care and quality of life. Nonlethal events such as ICD shock, sustained arrhythmia, or syncope were tabulated.

Patients were followed every three months for assessment of secondary endpoints, to record therapies delivered by the ICD and potential adverse effects of the ICD, and to assess compliance and potential adverse symptoms in patients treated with antiarrhythmic drugs. A 12-lead electrocardiogram was obtained every six months, and appropriate laboratory and pulmonary tests were performed at six and eighteen months on patients receiving amiodarone. The average follow-up was expected to be 2.6 years. Analysis was done by intention-to-treat. The outcome of primary interest in the subrandomization between sotalol and amiodarone was the time to withdrawal from assigned therapy.

After a review of the data by the Data and Safety Monitoring Board, the AVID study was stopped early on April 7, 1997 because of the findings that after one year, patients in the defibrillator group experienced a nearly 38 percent reduction in deaths compared to the group of patients taking an antiarrhythmic drug. The defibrillator group had about a 25 percent reduction in deaths in years two and three.

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 & women with VF, VT with syncope, or VT without syncope, but with ejection fraction less than or equal to .40 & systolic blood pressure less than 80 mm Hg, chest pain , or near syncope.

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: Treatment
  • Allocation: Randomized

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

September 1, 1992

Study Completion

August 1, 2002

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)

April 14, 2016

Last Update Submitted That Met QC Criteria

April 12, 2016

Last Verified

May 1, 2005

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 74

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: AVID
    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
  4. Manual of Procedures

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.

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