Beta 3 Agonist Treatment in Heart Failure
- Conditions
- Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
- Interventions
- Drug: Placebo
- Registration Number
- NCT01876433
- Lead Sponsor
- Henning Bundgaard
- 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
1. Determine safety of administration of Mirabegron to patients with heart failure.
2. Determine if treatment with Mirabegron for 6 months induces beneficial cardiac structural remodelling in patients with heart failure.
3. Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test in patients with heart failure.
4. Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with heart failure.
5. Determine effects of Mirabegron on circulating biomarkers in patients with heart failure.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
- 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
- >18 years
- 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 > 1. degree AV-block unless the patient has a pacemaker
- Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR< 50 ml/min/1,73 m2) diseases
- Heart failure due to uncorrected thyroid disease
- Cardiac mechanical support
- < 6 months after CRT
- Uncontrolled hypotension (defined as symptomatic systolic blood pressure < 90 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below)
- Body mass index (BMI) > 35
- Unable to give informed consent
- Reduced compliance
- All women of child bearing potential will be required to use adequate contraception
- Pregnant or lactating women
- Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2. Beta-3-agonist Mirabegron Mirabegron 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.
- Primary Outcome Measures
Name Time Method Increase in LVEF (measured by MRI or CT) 6 months
- Secondary Outcome Measures
Name Time Method 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 A reduction in LA volume 6 months A shortening of the QT interval 6 months Improvement in functional class 6 months A reduction in LV diameters 6 months Improvement in quality of life 6 monhs
Trial Locations
- Locations (3)
Monash Center of Cardiovascular Research.
🇦🇺Melbourne, Australia
Department of Cardiology, Royal North Shore Hospital.
🇦🇺Sydney, Australia
Department of Cardiology, The Heart Centre, Rigshospitalet Copenhagen University Hospital.
🇩🇰Copenhagen Ø, Denmark
Monash Center of Cardiovascular Research.🇦🇺Melbourne, Australia