Beta 3 Agonist Treatment in Heart Failure
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
- Sponsor
- Henning Bundgaard
- Enrollment
- 70
- Locations
- 3
- Primary Endpoint
- Increase in LVEF (measured by MRI or CT)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Objective: The objective of the study is to assess the structural and functional cardiac effects of treatment with the beta 3 AR agonist Mirabegron in patients with chronic heart failure.
Design: The investigators are planning a study aiming at establishing proof of concept that treatment of patients with HF with Mirabegron has significant positive effects, as assessed by clinical and biochemistry measurements, but not by hard endpoints. The investigators are performing a combined dose-finding - chronic efficacy study.
The study is a randomized, placebo-controlled, double-blinded trial. The follow-up period is 6 months. 70 patients with chronic heart failure will be included.
Specific aims
- Determine safety of administration of Mirabegron to patients with heart failure.
- Determine if treatment with Mirabegron for 6 months induces beneficial cardiac structural remodelling in patients with heart failure.
- Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test in patients with heart failure.
- Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with heart failure.
- Determine effects of Mirabegron on circulating biomarkers in patients with heart failure.
Investigators
Henning Bundgaard
Consultant, dr. med.
Rigshospitalet, Denmark
Eligibility Criteria
Inclusion Criteria
- •Stable heart failure NYHA class II-III on ischemic or non-ischemic basis
- •Left ventricular ejection fraction (LVEF) \< 40%
- •Stable sinus rhythm (SR)
- •On optimised evidence-based pharmacological HF treatment stable \> 4 weeks with no current plan for changing HF therapy. The therapy must include a beta-blocker.
- •No change in diuretics \< 4 weeks
Exclusion Criteria
- •Unstable cardiac condition
- •Acute myocardial infarction (AMI) or revascularisation \< 3 month ago
- •Atrial fibrillation (for technical reasons in relation to imaging and HR reporting)
- •Uncorrected significant primary obstructive valve disease
- •Planned major surgery including cardiac revascularisation
- •Hemodynamically significant obstructive cardiomyopathy
- •Stroke with significant neurological deficit
- •Acute myocarditis or constrictive pericarditis
- •Symptomatic bradycardia or \>
- •degree AV-block unless the patient has a pacemaker
Arms & Interventions
Placebo
Placebo 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.
Intervention: Placebo
Beta-3-agonist
Mirabegron 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.
Intervention: Mirabegron
Outcomes
Primary Outcomes
Increase in LVEF (measured by MRI or CT)
Time Frame: 6 months
Secondary Outcomes
- A shortening of the QT interval(6 months)
- A reduction in LA volume(6 months)
- A reduction in NT proBNP(6 months)
- An increase in 6 min walking distance(6 months)
- An increase in CO/SV(6 months)
- A reduction in LVIDd(6 months)
- An improvement in diastolic function(6 months)
- Improvement in functional class(6 months)
- Improvement in quality of life(6 monhs)
- A reduction in LV diameters(6 months)