Beta 3 Agonist Treatment in Heart Failure (Beat-HF)

Henning Bundgaard

Status and phase: Completed; Phase 2

Conditions: Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Treatments: Drug: Placebo; Drug: Mirabegron

Study type: Interventional

Funder types: Other

Identifiers

NCT01876433

2012-004805-29

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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70 participants in 2 patient groups, including a placebo group

Beta-3-agonist

Active Comparator group

Description:

Mirabegron 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.

Treatment:

Drug: Mirabegron

Placebo

Placebo Comparator group

Description:

Placebo 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.

Treatment:

Drug: Placebo