Completed

NCT Number: NCT03926754

Beta 3 Agonist Treatment in Heart Failure-2

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

1. Determine safety of administration of Mirabegron to patients with moderate to severe heart failure. 2. 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). 3. 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. 4. Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with moderate to severe heart failure. 5. Determine effects of Mirabegron on circulating biomarkers in patients with moderate to severe heart failure. 6. Determine the immediate and short term haemodynamic effects of Mirabron as measured by CT and invasively.

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Key information

Conditions

Heart Failure With Reduced Ejection Fraction NYHA Class III-IV

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Rigshospitalet

Copenhagen, 2100, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.
>18 years

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)
Unable to give informed consent
Reduced compliance
All women of child bearing potential will be required to use adequate contraception
Pregnant or lactating women
Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin.
Known allergy to iodine containing contrast
Estimated GFR < 30 ml/min/1.73 m2
Congenital or drug induced QT prolongation

Treatment and study plan

Mirabegron

Drug

Study A The maximum tolerated dose up to a maximum of 300 mg per day for 26 weeks.

Study B One single dose of 300 mg at day one followed by 150 mg x 2 for 1 week (8-11 days).

Other names: Placebo

Primary outcomes

Increase in left ventricular ejection fraction as measured by computed tomography

Time frame: 3 months

Study A
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.

Sponsors and collaborators

Lead sponsor

Henning Bundgaard

Other

Collaborators

Bornholm Hospital, Denmark
Herlev Hospital
Hillerød hospital, Denmark
Hvidovre University Hospital
Royal North Shore Hospital
University Hospital Bispebjerg and Frederiksberg

Registry information

Acronym: BEAT-HF II

Important dates

Study start: 2017
Primary completion: 2021
Study completion: 2021
First posted: Apr 24, 2019
Registry last updated: May 4, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.