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

Sponsor:	Royal Brompton & Harefield NHS Foundation Trust
Collaborator:	University of Oxford
Information provided by (Responsible Party):	Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00832442

Purpose

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.

Condition	Intervention
Heart Failure	Drug: Beta blocker Other: Placebo

Study Type:	Observational
Official Title:	Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure

Drug Information available for: Metoprolol Carvedilol Nebivolol

U.S. FDA Resources

Further study details as provided by Royal Brompton & Harefield NHS Foundation Trust:

Primary Outcome Measures:

Beta-blocker therapy improves overall mortality and morbidity in symptomatic heart failure in an individual patient meta-analysis [ Time Frame: variable (time to event) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Beta-blocker therapy improves mortality and morbidity in both elderly patients and women [ Time Frame: variable (time to event) ] [ Designated as safety issue: No ]
Beta-blocker therapy improves mortality and morbidity in patients with co-morbidities (diabetes, renal dysfunction, COPD, peripheral arterial disease or atrial fibrillation) [ Time Frame: variable (time to event) ] [ Designated as safety issue: No ]
The benefit of beta-blockers is not modified by concomitant cardiovascular therapy [ Time Frame: variable (time to event) ] [ Designated as safety issue: No ]
The benefit of beta-blockers is independent of left ventricular ejection fraction at baseline [ Time Frame: variable (time to event) ] [ Designated as safety issue: No ]
The clinical benefit is dependent on the resting heart rate achieved whatever the dose achieved or agent used [ Time Frame: variable (time to event) ] [ Designated as safety issue: No ]
Adverse side effects of beta blocker therapy do not significantly impact on clinical benefit (as a whole and in relevant sub-groups) [ Time Frame: variable (time to event) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	18240
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Beta blocker	Drug: Beta blocker as determined by individual study Other Names: Metoprolol Bucindolol Carvedilol Bisoprolol Nebivolol
Placebo	Other: Placebo in addition to usual care

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Meta-Analysis of randomised controlled trials investigating mortality & morbidity of placebo versus beta-blockers in heart failure

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00832442

Locations

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

Sponsors and Collaborators

Royal Brompton & Harefield NHS Foundation Trust

University of Oxford

Investigators

Study Chair:	Marcus Flather	Royal Brompton Hospital, London
Study Chair:	Luis Manzano	Universidad de Alcala, Madrid
Study Chair:	Dipak Kotecha	Royal Brompton Hospital, London
Study Chair:	Henry Krum	Monash University, Melbourne

More Information

Additional Information:

Clinical Trials & Evaluation Unit This link exits the ClinicalTrials.gov site

Monash Centre of Cardiovascular Research & Education (CCRE) in Therapeutics This link exits the ClinicalTrials.gov site

Publications:

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.

[No authors listed] 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.

[No authors listed] 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.

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.

[No authors listed] The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999 Jan 2;353(9146):9-13.

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.

[No authors listed] 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.

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.

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.

Responsible Party:	Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00832442 History of Changes
Other Study ID Numbers:	CTEU08/d5/BBHF
Study First Received:	January 28, 2009
Last Updated:	May 8, 2012
Health Authority:	United Kingdom: National Health Service

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:

Beta blocker
Heart Failure
Meta analysis
Individual patient data

Additional relevant MeSH terms:

Heart Failure
Heart Diseases
Cardiovascular Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists

Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2012