Beta 3 Agonist Treatment in Heart Failure-2
Overview
- Phase
- Phase 2
- Intervention
- Mirabegron
- Conditions
- Heart Failure With Reduced Ejection Fraction NYHA Class III-IV
- Sponsor
- Henning Bundgaard
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Change in invasive hemodynamics assesses by right heart catherization
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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 moderate to severe chronic heart failure (LVEF<35%, NYHA III-IV).
The study is a randomized, placebo-controlled, double-blinded trial in two phases with two hypotheses:
Chronic study - study A: Long-term treatment (3 months) with the β3 adrenergic receptor agonist Mirabegron is beneficial in patients with moderate to severe human heart failure
Invasive study - Study B: Administration of Mirabegron in patients with heart failure leads to an immediate increase in cardiac output at a constant or reduced left ventricular filling pressure during submaximal exercise
Specific aims
- Determine safety of administration of Mirabegron to patients with moderate to severe heart failure.
- Determine if treatment with Mirabegron for 3 months induces beneficial cardiac structural remodelling in patients with moderate to severe heart failure. In an open-label follow-up to determine the effects of Mirabegron after an extended duration (a total of 12 months).
- Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test in patients with moderate to severe heart failure.
- Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with moderate to severe heart failure.
- Determine effects of Mirabegron on circulating biomarkers in patients with moderate to severe heart failure.
- Determine the immediate and short term haemodynamic effects of Mirabron as measured by CT and invasively.
Investigators
Henning Bundgaard
Professor
Rigshospitalet, Denmark
Eligibility Criteria
Inclusion Criteria
- •Stable heart failure NYHA class III-IV on ischemic or non-ischemic basis
- •Left ventricular ejection fraction (LVEF) \< 35% as assessed by cardiac CT
- •NT proBNP \> 1000 pg/ml
- •On optimised evidence-based pharmacological HF treatment stable ≥2 weeks with no current plan for changing HF therapy. The therapy must include a beta-blocker.
- •No change in diuretics ≤1 week
- •No admittances to hospital for treatment with intravenously administered positive inotropic agents ≤ 4 weeks.
Exclusion Criteria
- •Acute myocardial infarction (AMI) or revascularisation \< 3 month ago
- •Uncorrected significant primary obstructive valve disease
- •Planned major surgery including cardiac revascularisation
- •Hemodynamically significant obstructive cardiomyopathy
- •Acute myocarditis or constrictive pericarditis
- •Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR\< 30 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 \< 80 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below)
Arms & Interventions
Mirabegron
Active treatment arm (mirabegron)
Intervention: Mirabegron
Placebo
Placebo
Intervention: Mirabegron
Outcomes
Primary Outcomes
Change in invasive hemodynamics assesses by right heart catherization
Time Frame: At 3 hours and at 1 week
Study B is explorative assessing the effect on invasive parameters including cardiac output, pulmonary wedge pressure and pulmonary and systemic vascular resistance.
Increase in left ventricular ejection fraction as measured by computed tomography
Time Frame: 3 months
Study A