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

• Conditions: Heart Failure
• Interventions: Other: Placebo; Drug: Beta blocker

• Registration Number: NCT00832442
• Lead Sponsor: Royal Brompton & Harefield NHS Foundation Trust

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08
• Status Verified: 2009-01
• Study First Submitted: 2009-01-28
• Study First Submitted QC: 2009-01-29
• Study First Posted: 2009-01-30
• Last Update Submitted: 2012-05-08
• Last Update Posted: 2012-05-09
• Primary Completion: 2012-12
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18240

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

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Beta blocker	Beta blocker	-

Primary Outcome Measures

Name	Time	Method
Beta-blocker therapy improves overall mortality and morbidity in symptomatic heart failure in an individual patient meta-analysis	variable (time to event)

Secondary Outcome Measures

Name	Time	Method
Beta-blocker therapy improves mortality and morbidity in both elderly patients and women	variable (time to event)
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)
The benefit of beta-blockers is not modified by concomitant cardiovascular therapy	variable (time to event)
The benefit of beta-blockers is independent of left ventricular ejection fraction at baseline	variable (time to event)
The clinical benefit is dependent on the resting heart rate achieved whatever the dose achieved or agent used	variable (time to event)
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)

Trial Locations

Locations (2)

Clinical Trials & Evaluation Unit, Royal Brompton Hospital; 🇬🇧 London, United Kingdom

Centre for Statistics in Medicine, University of Oxford; 🇬🇧 Oxford, United Kingdom