Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
Conditions
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.
Interventions
DRUGMirabegron
DRUGPlacebo
Sponsors
Henning Bundgaard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Stable heart failure NYHA class II-III on ischemic or non-ischemic basis 2. Left ventricular ejection fraction (LVEF) \< 40% 3. Stable sinus rhythm (SR) 4. 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. 5. No change in diuretics \< 4 weeks 6. \>18 years
Exclusion criteria
1. Unstable cardiac condition 2. Acute myocardial infarction (AMI) or revascularisation \< 3 month ago 3. Atrial fibrillation (for technical reasons in relation to imaging and HR reporting) 4. Uncorrected significant primary obstructive valve disease 5. Planned major surgery including cardiac revascularisation 6. Hemodynamically significant obstructive cardiomyopathy 7. Stroke with significant neurological deficit 8. Acute myocarditis or constrictive pericarditis 9. Symptomatic bradycardia or \> 1. degree AV-block unless the patient has a pacemaker 10. Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR\< 50 ml/min/1,73 m2) diseases 11. Heart failure due to uncorrected thyroid disease 12. Cardiac mechanical support 13. \< 6 months after CRT 14. 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) 15. Body mass index (BMI) \> 35 16. Unable to give informed consent 17. Reduced compliance 18. All women of child bearing potential will be required to use adequate contraception 19. Pregnant or lactating women 20. Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Increase in LVEF (measured by MRI or CT) | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 NT proBNP | 6 months |
| A reduction in LV diameters | 6 months |
| A shortening of the QT interval | 6 months |
| Improvement in quality of life | 6 monhs |
| Improvement in functional class | 6 months |
| A reduction in LA volume | 6 months |
Countries
Australia, Denmark
Outcome results
None listed