Clinical trial NCT00000531: Antiarrhythmics Versus Implantable Defibrillators (AVID)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arrhythmia
Cardiovascular Diseases
Death, Sudden, Cardiac
Heart Diseases
Tachycardia, Ventricular
Ventricular Fibrillation
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 1999-10-28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Washington
name: Alfred Hallstrom
References:
citation: Hallstrom AP, Greene HL, Wyse DG, Zipes D, Epstein AE, Domanski MJ, Schron EB; AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators (AVID)--rationale, design, and methods. Am J Cardiol. 1995 Mar 1;75(7):470-5.
citation: Mower MM. AVID necessity. Pacing Clin Electrophysiol. 1994 Feb;17(2):258-60; author reply 262-6. doi: 10.1111/j.1540-8159.1994.tb01381.x. No abstract available.
citation: Fogoros RN. An AVID dissent. Pacing Clin Electrophysiol. 1994 Nov;17(11 Pt 1):1707-11. doi: 10.1111/j.1540-8159.1994.tb03736.x.
citation: Connolly SJ. "An AVID dissent": commentary. Pacing Clin Electrophysiol. 1994 Nov;17(11 Pt 1):1712-3. doi: 10.1111/j.1540-8159.1994.tb03737.x.
citation: Singer I. AVID necessity. Pacing Clin Electrophysiol. 1994 Feb;17(2):260-2; author reply 262-6. doi: 10.1111/j.1540-8159.1994.tb01382.x. No abstract available.
citation: Brooks MM, Hallstrom A, Peckova M. A simulation study used to design the sequential monitoring plan for a clinical trial. Stat Med. 1995 Oct 30;14(20):2227-37. doi: 10.1002/sim.4780142006.
citation: Curtis AB, Hallstrom AP, Klein RC, Nath S, Pinski SL, Epstein AE, Wyse G, Cannom DS, Renfroe E. Influence of patient characteristics in the selection of patients for defibrillator implantation (the AVID Registry). Antiarrhythmics Versus Implantable Defibrillators. Am J Cardiol. 1997 May 1;79(9):1185-9. doi: 10.1016/s0002-9149(97)00079-9.
citation: Josephson ME, Nisam S. The AVID trial: evidence based or randomized control trials--is the AVID study too late? Antiarrhythmics Versus Implantable Defibrillators. Am J Cardiol. 1997 Jul 15;80(2):194-7. doi: 10.1016/s0002-9149(97)00341-x.
citation: Are implantable cardioverter-defibrillators or drugs more effective in prolonging life? The Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial Executive Committee. Am J Cardiol. 1997 Mar 1;79(5):661-3. No abstract available.
citation: Domanski MJ, Saksena S, Wyse G, Hallstrom A, Schron EB, Nanda A, Nanda A, Kutalek S. Clinical and socioeconomic profile of patients with malignant ventricular arrhythmias in 1993 to 1995. AVID investigators. Antiarrhythmics Versus Implantable Defibrillator. Am J Cardiol. 1997 Aug 1;80(3):299-301. doi: 10.1016/s0002-9149(97)00349-4.
citation: Kim SG, Hallstrom A, Love JC, Rosenberg Y, Powell J, Roth J, Brodsky M, Moore R, Wilkoff B. Comparison of clinical characteristics and frequency of implantable defibrillator use between randomized patients in the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial and nonrandomized registry patients. Am J Cardiol. 1997 Aug 15;80(4):454-7. doi: 10.1016/s0002-9149(97)00394-9.
citation: Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997 Nov 27;337(22):1576-83. doi: 10.1056/NEJM199711273372202.
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citation: Jenkins LS, Steinberg JS, Kutalek SP, et al: Quality of life in patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. Circulation 1997;96:I-439
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citation: Anderson JL, Hallstrom AP, Epstein AE, Pinski SL, Rosenberg Y, Nora MO, Chilson D, Cannom DS, Moore R. Design and results of the antiarrhythmics vs implantable defibrillators (AVID) registry. The AVID Investigators. Circulation. 1999 Apr 6;99(13):1692-9. doi: 10.1161/01.cir.99.13.1692.
citation: Domanski MJ, Sakseena S, Epstein AE, Hallstrom AP, Brodsky MA, Kim S, Lancaster S, Schron E. Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol. 1999 Oct;34(4):1090-5. doi: 10.1016/s0735-1097(99)00327-7.
citation: Epstein AE, Powell J, Yao Q, Ocampo C, Lancaster S, Rosenberg Y, Cannom DS, Herre JM, Greene HL. In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival: results from the AVID Registry. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol. 1999 Oct;34(4):1111-6. doi: 10.1016/s0735-1097(99)00305-8.
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citation: Pinski SL, Yao Q, Epstein AE, Lancaster S, Greene HL, Pacifico A, Cook JR, Jadonath R, Marinchak RA. Determinants of outcome in patients with sustained ventricular tachyarrhythmias: the antiarrhythmics versus implantable defibrillators (AVID) study registry. Am Heart J. 2000 May;139(5):804-13. doi: 10.1016/s0002-8703(00)90011-5.
citation: Raitt MH, Renfroe EG, Epstein AE, McAnulty JH, Mounsey P, Steinberg JS, Lancaster SE, Jadonath RL, Hallstrom AP; Antiarrhythmics Versus Implantable Defibrillators investigators. "Stable" ventricular tachycardia is not a benign rhythm : insights from the antiarrhythmics versus implantable defibrillators (AVID) registry. Circulation. 2001 Jan 16;103(2):244-52. doi: 10.1161/01.cir.103.2.244.
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citation: Mitchell LB, Powell JL, Gillis AM, Kehl V, Hallstrom AP; AVID Investigators. Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol. 2003 Jul 2;42(1):81-7. doi: 10.1016/s0735-1097(03)00498-4.
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