Beta-Blocker Evaluation in Survival Trial (BEST)

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000560

Collaborator

(none)

Duration (Months)

Study Details

Study Description

Brief Summary

To determine if addition of a beta-blocker to standard therapy in Class III and Class IV heart failure patients reduced total mortality.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Heart Diseases Heart Failure, Congestive Heart Failure	Drug: adrenergic beta antagonists	Phase 3

Detailed Description

BACKGROUND:

Controlled and uncontrolled studies suggested that beta-blockade improves ventricular function in congestive heart failure. Several trials suggested that beta-blockers may also reduce mortality. In the Beta-Blocker Heart Attack Trial, patients with a history of heart failure had less cardiac and sudden-death mortality than those who did not. Patients with a low ejection fraction in the Cardiac Arrhythmia Suppression Trial who were treated with beta-blockade also had a reduction in mortality. The Metoprolol in Dilated Cardiomyopathy trial randomized patients with dilated cardiomyopathies to treatment with metoprolol or placebo. There was a trend toward reduction in a morbidity and mortality endpoint in patients treated with metoprolol, but this was due entirely to a reduction in the need for cardiac transplantation. Thus, despite a reasonable theoretical basis and suggestive clinical studies, the concept that beta-blockers reduced mortality in congestive heart failure patients was unproved.

DESIGN NARRATIVE:

Randomized, double-blind, multicenter. Patients were assigned to standard therapy plus the addition of a beta-blocker (bucindolol) versus a placebo. The primary endpoint was total mortality. A radionuclide ventriculogram was performed within 60 days of randomization. History, physical examination, clinical laboratory studies, chest x-ray, electrocardiogram, and plasma norepinephrine levels were obtained within 14 days of randomization. Patients were stratified by hospital, congestive heart failure etiology, ejection fraction, and gender, and were assigned to a treatment group by an adaptive balancing scheme ("biased coin" randomization). Patients were randomized to either placebo plus standard congestive heart failure treatment or to the beta-blocker plus standard congestive heart failure treatment and followed for a minimum of 18 months. The over three year recruitment period began in May 1995 at the first 35 sites. An additional 55 sites began recruitment on August 14, 1995. Recruitment ended in December, 1998 with the enrollment of 2,708 patients.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Study Start Date :

Jun 1, 1994

Study Completion Date :

Sep 1, 1999

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Men and women, ages 18 and over. Patients had compensated congestive heart failure due to idiopathic dilated cardiomyopathy or coronary disease with ejection fraction less than or equal to 0.35, were in the New York Heart Association functional class III or IV, and were taking an angiotensin-converting enzyme inhibitor, digitalis, and if needed, a diuretic. Patients with a specific indication for, or contraindication to, beta-blockade were excluded.