Beta 3 Agonist Treatment in Heart Failure

NCT ID: NCT01876433

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2015-09-30

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.

Conditions

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Beta-3-agonist

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

Group Type: ACTIVE_COMPARATOR

Mirabegron

Intervention Type: DRUG

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Mirabegron

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Beta 3 agonist

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Henning Bundgaard

OTHER

Sponsor Role: lead

Responsible Party

Henning Bundgaard

Consultant, dr. med.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Henning Bundgaard, MD, PhD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet Copenhagen University Hospital, Department of Cardiology

Locations

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

Countries

Australia; Denmark

References

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.

Reference Type: DERIVED

PMID: 38452283 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27990717 (View on PubMed)

Other Identifiers

2012-004805-29

Identifier Type: -

Identifier Source: org_study_id