Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure

Heart Failure Clinical Trial

— BB-META-HF  

Official title:

Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT00832442
• Other study ID #: CTEU08/d5/BBHF
• Status: Enrolling by invitation
• Phase: N/A
• First received: January 28, 2009
• Last updated: May 8, 2012
• Start date: August 2008
• Est. completion date: December 2012

Study information

• Verified date: January 2009
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Health Service
• Study type: Observational

Clinical Trial Summary

Several large trials have shown that beta-blocker treatment reduces the risk of death and hospital admission in patients with symptomatic heart failure. Unfortunately, survey data suggests relatively poor utilisation of beta-blockers, despite ample evidence for good tolerability. Additionally there are several important unanswered questions, such as clinical efficacy for specific sub-populations (women, the elderly and patients with diabetes or other co-morbidities) and the effect of beta-blockers in combination with other medications. Previous meta-analyses, based on published tabular data, have been conducted although this approach has important biases and limitations.

We plan to perform a carefully conducted systematic review of individual patient data from the major randomised trials of beta-blockers in heart failure. The goals of this collaborative project are to clarify the overall efficacy of beta-blockers and identify sub-groups that show particular benefit, thereby increasing the use of beta-blockers, reducing adverse clinical outcomes and the high costs associated with this condition.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 18240
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Randomised control trials of beta-blocker versus control in patients with documented heart failure

• Unconfounded trials only (in which one treatment group differed from another only by the beta-blocker therapy of interest)

• Randomization process precluded prior knowledge of the next treatment (for example trials in which treatment allocation was alternate or based on odd or even dates would not be included)

Exclusion Criteria:

• Trial sample size of less than 300 patients

Study Design

N/A

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Beta blocker
as determined by individual study

Other:
• Placebo
in addition to usual care

Locations

Country	Name	City	State
United Kingdom	Clinical Trials & Evaluation Unit, Royal Brompton Hospital	London
United Kingdom	Centre for Statistics in Medicine, University of Oxford	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust	University of Oxford

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees. Circulation. 1994 Oct;90(4):1765-73. — View Citation

Beta-Blocker Evaluation of Survival Trial Investigators. 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. — View Citation

Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001 May 5;357(9266):1385-90. — View Citation

Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Böhm M, Anker SD, Thompson SG, Poole-Wilson PA; SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005 Feb;26(3):215-25. Epub 2005 Jan 9. — View Citation

Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996 May 23;334(21):1349-55. — View Citation

Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL; Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. — View Citation

Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet. 1997 Feb 8;349(9049):375-80. — View Citation

The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999 Jan 2;353(9146):9-13. — View Citation

Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, Gilbert EM, Johnson MR, Goss FG, Hjalmarson A. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group. Lancet. 1993 Dec 11;342(8885):1441-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beta-blocker therapy improves overall mortality and morbidity in symptomatic heart failure in an individual patient meta-analysis		variable (time to event)	No
Secondary	Beta-blocker therapy improves mortality and morbidity in both elderly patients and women		variable (time to event)	No
Secondary	Beta-blocker therapy improves mortality and morbidity in patients with co-morbidities (diabetes, renal dysfunction, COPD, peripheral arterial disease or atrial fibrillation)		variable (time to event)	No
Secondary	The benefit of beta-blockers is not modified by concomitant cardiovascular therapy		variable (time to event)	No
Secondary	The benefit of beta-blockers is independent of left ventricular ejection fraction at baseline		variable (time to event)	No
Secondary	The clinical benefit is dependent on the resting heart rate achieved whatever the dose achieved or agent used		variable (time to event)	No
Secondary	Adverse side effects of beta blocker therapy do not significantly impact on clinical benefit (as a whole and in relevant sub-groups)		variable (time to event)	Yes

External Links

•   Clinical Trials & Evaluation Unit
•   Monash Centre of Cardiovascular Research & Education (CCRE) in Therapeutics