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AzTrials

Cardiovascular DiseasesPhase 3NCT00000560

Beta-Blocker Evaluation in Survival Trial (BEST)

A Phase 3 study testing adrenergic beta antagonists in people with Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 100 years
What is being tested?
adrenergic beta antagonists
How many people
Not given
Where
No sites listed yet
Study dates
Jun 1994to Sep 1999
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

About this study

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

Read the 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.

Being tested
adrenergic beta antagonists
Medical subject headings
Cardiovascular Diseases, Heart Diseases, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • adrenergic beta antagonistsDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 1999 (estimated)
  2. Study startJun 1994
  3. Study completionSep 1999

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Allocation
Randomised
Masking
Double blind
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000560
Sponsor's protocol ID
104
Status last verified
Apr 2005
First submitted
27 Oct 1999
Last updated
14 Apr 2016
Results posted
No

Publications

  • Design of the Beta-Blocker Evaluation Survival Trial (BEST). The BEST Steering Committee. Am J Cardiol. 1995 Jun 15;75(17):1220-3. doi: 10.1016/s0002-9149(99)80766-8.

    PubMed 7778543

  • Beta-Blocker Evaluation of Survival Trial Investigators; Eichhorn EJ, Domanski MJ, Krause-Steinrauf H, Bristow MR, Lavori PW. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001 May 31;344(22):1659-67. doi: 10.1056/NEJM200105313442202.

    PubMed 11386264

  • Aranda JM, Krause-Steinrauf HJ, Greenberg BH, Heng MK, Kosolcharoen PK, Renlund DG, Thaneemit-Chen S, White M, Cintron GB. Comparison of the beta blocker bucindolol in younger versus older patients with heart failure. Am J Cardiol. 2002 Jun 1;89(11):1322-6. doi: 10.1016/s0002-9149(02)02339-1. No abstract available.

    PubMed 12031741

  • Anderson JL, Krause-Steinrauf H, Goldman S, Clemson BS, Domanski MJ, Hager WD, Murray DR, Mann DL, Massie BM, McNamara DM, Oren R, Rogers WJ; Beta-Blocker Evaluation of Survival Trial (BEST) Investigators. Failure of benefit and early hazard of bucindolol for Class IV heart failure. J Card Fail. 2003 Aug;9(4):266-77. doi: 10.1054/jcaf.2003.42.

    PubMed 13680547

  • Domanski M, Krause-Steinrauf H, Deedwania P, Follmann D, Ghali JK, Gilbert E, Haffner S, Katz R, Lindenfeld J, Lowes BD, Martin W, McGrew F, Bristow MR; BEST Investigators. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. J Am Coll Cardiol. 2003 Sep 3;42(5):914-22. doi: 10.1016/s0735-1097(03)00856-8.

    PubMed 12957443

  • Eichhorn EJ, Grayburn PA, Mayer SA, St John Sutton M, Appleton C, Plehn J, Oh J, Greenberg B, DeMaria A, Frantz R, Krause-Steinrauf H. Myocardial contractile reserve by dobutamine stress echocardiography predicts improvement in ejection fraction with beta-blockade in patients with heart failure: the Beta-Blocker Evaluation of Survival Trial (BEST). Circulation. 2003 Nov 11;108(19):2336-41. doi: 10.1161/01.CIR.0000097111.00170.7B. Epub 2003 Nov 3.

    PubMed 14597587

  • Ghali JK, Krause-Steinrauf HJ, Adams KF, Khan SS, Rosenberg YD, Yancy CW, Young JB, Goldman S, Peberdy MA, Lindenfeld J. Gender differences in advanced heart failure: insights from the BEST study. J Am Coll Cardiol. 2003 Dec 17;42(12):2128-34. doi: 10.1016/j.jacc.2003.05.012.

    PubMed 14680739

  • Lindenfeld J, Ghali JK, Krause-Steinrauf HJ, Khan S, Adams K, Goldman S, Peberdy MA, Yancy C, Thaneemit-Chen S, Larsen RL, Young J, Lowes B, Rosenberg YD; BEST Investigators. Hormone replacement therapy is associated with improved survival in women with advanced heart failure. J Am Coll Cardiol. 2003 Oct 1;42(7):1238-45. doi: 10.1016/s0735-1097(03)00938-0.

    PubMed 14522488

  • Bristow MR, Krause-Steinrauf H, Nuzzo R, Liang CS, Lindenfeld J, Lowes BD, Hattler B, Abraham WT, Olson L, Krueger S, Thaneemit-Chen S, Hare JM, Loeb HS, Domanski MJ, Eichhorn EJ, Zelis R, Lavori P. Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial. Circulation. 2004 Sep 14;110(11):1437-42. doi: 10.1161/01.CIR.0000141297.50027.A4. Epub 2004 Aug 30.

    PubMed 15337700

  • O'Connor CM, Gottlieb S, Bourque JM, Krause-Steinrauf H, Anand I, Anderson JL, Plehn JF, Silver MA, White M, Carson P; BEST Investigators. Impact of nonfatal myocardial infarction on outcomes in patients with advanced heart failure and the effect of bucindolol therapy. Am J Cardiol. 2005 Mar 1;95(5):558-64. doi: 10.1016/j.amjcard.2004.11.001.

    PubMed 15721091

  • Grayburn PA, Appleton CP, DeMaria AN, Greenberg B, Lowes B, Oh J, Plehn JF, Rahko P, St John Sutton M, Eichhorn EJ; BEST Trial Echocardiographic Substudy Investigators. Echocardiographic predictors of morbidity and mortality in patients with advanced heart failure: the Beta-blocker Evaluation of Survival Trial (BEST). J Am Coll Cardiol. 2005 Apr 5;45(7):1064-71. doi: 10.1016/j.jacc.2004.12.069.

    PubMed 15808765

  • Kristensen SL, Rorth R, Jhund PS, Shen L, Lee MMY, Petrie MC, Kober L, McMurray JJV; BEST Investigators. Microvascular complications in diabetes patients with heart failure and reduced ejection fraction-insights from the Beta-blocker Evaluation of Survival Trial. Eur J Heart Fail. 2018 Nov;20(11):1549-1556. doi: 10.1002/ejhf.1201. Epub 2018 May 4.

    PubMed 29727039

  • Shen L, Jhund PS, Mogensen UM, Kober L, Claggett B, Rogers JK, McMurray JJV. Re-Examination of the BEST Trial Using Composite Outcomes, Including Emergency Department Visits. JACC Heart Fail. 2017 Aug;5(8):591-599. doi: 10.1016/j.jchf.2017.04.005.

    PubMed 28774394

  • Breathett K, Allen LA, Udelson J, Davis G, Bristow M. Changes in Left Ventricular Ejection Fraction Predict Survival and Hospitalization in Heart Failure With Reduced Ejection Fraction. Circ Heart Fail. 2016 Oct;9(10):e002962. doi: 10.1161/CIRCHEARTFAILURE.115.002962.

    PubMed 27656000

  • Jones LG, Sin MK, Hage FG, Kheirbek RE, Morgan CJ, Zile MR, Wu WC, Deedwania P, Fonarow GC, Aronow WS, Prabhu SD, Fletcher RD, Ahmed A, Allman RM. Characteristics and outcomes of patients with advanced chronic systolic heart failure receiving care at the Veterans Affairs versus other hospitals: insights from the Beta-blocker Evaluation of Survival Trial (BEST). Circ Heart Fail. 2015 Jan;8(1):17-24. doi: 10.1161/CIRCHEARTFAILURE.114.001300. Epub 2014 Dec 5.

    PubMed 25480782

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing adrenergic beta antagonists in people with Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000560, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2016.

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