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

NCT ID: NCT00832442

Last Updated: 2012-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

18240 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-08-31

Study Completion Date

2012-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Heart Failure

Study Groups

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Beta blocker

Beta blocker

Intervention Type DRUG

as determined by individual study

Placebo

Placebo

Intervention Type OTHER

in addition to usual care

Interventions

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Beta blocker

as determined by individual study

Intervention Type DRUG

Placebo

in addition to usual care

Intervention Type OTHER

Other Intervention Names

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Metoprolol Bucindolol Carvedilol Bisoprolol Nebivolol

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role collaborator

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marcus Flather

Role: STUDY_CHAIR

Royal Brompton Hospital, London

Luis Manzano

Role: STUDY_CHAIR

Universidad de Alcala, Madrid

Dipak Kotecha

Role: STUDY_CHAIR

Royal Brompton Hospital, London

Henry Krum

Role: STUDY_CHAIR

Monash University, Melbourne

Locations

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Clinical Trials & Evaluation Unit, Royal Brompton Hospital

London, , United Kingdom

Site Status

Centre for Statistics in Medicine, University of Oxford

Oxford, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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. doi: 10.1016/0140-6736(93)92930-r.

Reference Type BACKGROUND
PMID: 7902479 (View on PubMed)

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. doi: 10.1161/01.cir.90.4.1765.

Reference Type BACKGROUND
PMID: 7923660 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9033462 (View on PubMed)

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. doi: 10.1056/NEJM199605233342101.

Reference Type BACKGROUND
PMID: 8614419 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 10023943 (View on PubMed)

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. doi: 10.1056/NEJM200105313442201.

Reference Type BACKGROUND
PMID: 11386263 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11386264 (View on PubMed)

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, Bohm 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. doi: 10.1093/eurheartj/ehi115. Epub 2005 Jan 9.

Reference Type BACKGROUND
PMID: 15642700 (View on PubMed)

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. doi: 10.1016/s0140-6736(00)04560-8.

Reference Type BACKGROUND
PMID: 11356434 (View on PubMed)

Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H. A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential. Eur J Heart Fail. 2022 Mar;24(3):466-480. doi: 10.1002/ejhf.2417. Epub 2022 Jan 26.

Reference Type DERIVED
PMID: 34969173 (View on PubMed)

Karwath A, Bunting KV, Gill SK, Tica O, Pendleton S, Aziz F, Barsky AD, Chernbumroong S, Duan J, Mobley AR, Cardoso VR, Slater K, Williams JA, Bruce EJ, Wang X, Flather MD, Coats AJS, Gkoutos GV, Kotecha D; card AIc group and the Beta-blockers in Heart Failure Collaborative Group. Redefining beta-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis. Lancet. 2021 Oct 16;398(10309):1427-1435. doi: 10.1016/S0140-6736(21)01638-X. Epub 2021 Aug 30.

Reference Type DERIVED
PMID: 34474011 (View on PubMed)

Kotecha D, Manzano L, Krum H, Rosano G, Holmes J, Altman DG, Collins PD, Packer M, Wikstrand J, Coats AJ, Cleland JG, Kirchhof P, von Lueder TG, Rigby AS, Andersson B, Lip GY, van Veldhuisen DJ, Shibata MC, Wedel H, Bohm M, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis. BMJ. 2016 Apr 20;353:i1855. doi: 10.1136/bmj.i1855.

Reference Type DERIVED
PMID: 27098105 (View on PubMed)

Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, Lip GY, Coats AJ, Andersson B, Kirchhof P, von Lueder TG, Wedel H, Rosano G, Shibata MC, Rigby A, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Efficacy of beta blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014 Dec 20;384(9961):2235-43. doi: 10.1016/S0140-6736(14)61373-8. Epub 2014 Sep 2.

Reference Type DERIVED
PMID: 25193873 (View on PubMed)

Kotecha D, Manzano L, Altman DG, Krum H, Erdem G, Williams N, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design. Syst Rev. 2013 Jan 18;2:7. doi: 10.1186/2046-4053-2-7.

Reference Type DERIVED
PMID: 23327629 (View on PubMed)

Other Identifiers

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CTEU08/d5/BBHF

Identifier Type: -

Identifier Source: org_study_id

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