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Beta 3 Agonist Treatment in Heart Failure

Phase 2
Completed
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
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.
Beta-3-agonistMirabegronMirabegron 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.
Primary Outcome Measures
NameTimeMethod
Increase in LVEF (measured by MRI or CT)6 months
Secondary Outcome Measures
NameTimeMethod
A reduction in NT proBNP6 months
An increase in 6 min walking distance6 months
An increase in CO/SV6 months
A reduction in LVIDd6 months
An improvement in diastolic function6 months
A reduction in LA volume6 months
A shortening of the QT interval6 months
Improvement in functional class6 months
A reduction in LV diameters6 months
Improvement in quality of life6 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

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