Beta 3 Agonist Treatment in Heart Failure

NCT01876433 | Completed Phase 2 DMC

• 1 other identifier: 2012-004805-29
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 3

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. 1.Determine safety of administration of Mirabegron to patients with heart failure.
2. 2.Determine if treatment with Mirabegron for 6 months induces beneficial cardiac structural remodelling in patients with heart failure.
3. 3.Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test in patients with heart failure.
4. 4.Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with heart failure.
5. 5.Determine effects of Mirabegron on circulating biomarkers in patients with heart failure.

Conditions

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Outcome Measures

Primary Outcomes (1)

• Increase in LVEF (measured by MRI or CT)

  6 months

Secondary Outcomes (10)

• A reduction in NT proBNP

  6 months

• An increase in 6 min walking distance

  6 months

• An increase in CO/SV

  6 months

• A reduction in LVIDd

  6 months

• An improvement in diastolic function

  6 months

Study Arms (2)

Beta-3-agonist

ACTIVE COMPARATOR

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

Drug: Mirabegron

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Mirabegron DRUG

Also known as: Beta 3 agonist

Beta-3-agonist

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stable heart failure NYHA class II-III on ischemic or non-ischemic basis
• Left ventricular ejection fraction (LVEF) \< 40%
• Stable sinus rhythm (SR)
• 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.
• No change in diuretics \< 4 weeks
• \>18 years

You may not qualify if:

• Unstable cardiac condition
• Acute myocardial infarction (AMI) or revascularisation \< 3 month ago
• Atrial fibrillation (for technical reasons in relation to imaging and HR reporting)
• Uncorrected significant primary obstructive valve disease
• Planned major surgery including cardiac revascularisation
• Hemodynamically significant obstructive cardiomyopathy
• Stroke with significant neurological deficit
• Acute myocarditis or constrictive pericarditis
• Symptomatic bradycardia or \> 1. degree AV-block unless the patient has a pacemaker
• Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR\< 50 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 \< 90 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below)
• Body mass index (BMI) \> 35

Sponsors & Collaborators

• Henning Bundgaard: lead

Study Sites (3)

Monash Center of Cardiovascular Research.

Melbourne, Australia

Location

Department of Cardiology, Royal North Shore Hospital.

Sydney, Australia

Location

Department of Cardiology, The Heart Centre, Rigshospitalet Copenhagen University Hospital.

Copenhagen Ø, 2100, Denmark

Location

Related Publications (2)

• Bahrami HSZ, Hasselbalch RB, Soholm H, Thomsen JH, Sorgaard M, Kofoed KF, Valeur N, Boesgaard S, Fry NAS, Moller JE, Raja AA, Kober L, Iversen K, Rasmussen H, Bundgaard H. First-In-Man Trial of beta3-Adrenoceptor Agonist Treatment in Chronic Heart Failure: Impact on Diastolic Function. J Cardiovasc Pharmacol. 2024 May 1;83(5):466-473. doi: 10.1097/FJC.0000000000001545.

  PMID: 38452283 DERIVED

• Bundgaard H, Axelsson A, Hartvig Thomsen J, Sorgaard M, Kofoed KF, Hasselbalch R, Fry NA, Valeur N, Boesgaard S, Gustafsson F, Kober L, Iversen K, Rasmussen HH. The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial. Eur J Heart Fail. 2017 Apr;19(4):566-575. doi: 10.1002/ejhf.714. Epub 2016 Dec 18.

  PMID: 27990717 DERIVED

MeSH Terms

Interventions

mirabegron; Adrenergic beta-3 Receptor Agonists

Intervention Hierarchy (Ancestors)

Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Officials

• Henning Bundgaard, MD, PhD, DMSc

  Rigshospitalet Copenhagen University Hospital, Department of Cardiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant, dr. med.

Study Record Dates

• First Submitted: June 10, 2013
• First Posted: June 12, 2013
• Study Start: September 30, 2013
• Primary Completion: September 30, 2015
• Study Completion: September 30, 2015
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

DK (1); AU (2)