Beta 3 Agonist Treatment in Heart Failure

• Status: Completed
• Trial end date: 2015-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Henning Bundgaard
• Collaborators: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia; Monash Center of Cardiovascular Research, Melbourne, Australia.
• Treatments: Mirabegron

Criteria

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.