Beat-HF: Beta 3 Agonist Treatment in Heart Failure

• Sponsor: Henning Bundgaard (Other)
• Overall Status: Completed
• CT.gov ID: NCT01876433
• Collaborator: (none)
• Enrollment: 70
• Locations: 3
• Arms: 2
• Actual Duration (Months): 24
• Patients Per Site: 23.3
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)	Drug: Mirabegron; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Beta 3 Agonist Treatment in Heart Failure
• Actual Study Start Date: Sep 30, 2013
• Actual Primary Completion Date: Sep 30, 2015
• Actual Study Completion Date: Sep 30, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Beta-3-agonist Mirabegron 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.	Drug: Mirabegron; Other Names: Beta 3 agonist
Placebo Comparator: Placebo Placebo 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Increase in LVEF (measured by MRI or CT) [6 months]

Secondary Outcome Measures

1. A reduction in NT proBNP [6 months]

2. An increase in 6 min walking distance [6 months]

3. An increase in CO/SV [6 months]

4. A reduction in LVIDd [6 months]

5. An improvement in diastolic function [6 months]

6. A reduction in LA volume [6 months]

7. A reduction in LV diameters [6 months]

8. A shortening of the QT interval [6 months]

9. Improvement in quality of life [6 monhs]

10. Improvement in functional class [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Monash Center of Cardiovascular Research.	Melbourne		Australia
2	Department of Cardiology, Royal North Shore Hospital.	Sydney		Australia
3	Department of Cardiology, The Heart Centre, Rigshospitalet Copenhagen University Hospital.	Copenhagen Ø		Denmark	2100

Sponsors and Collaborators

• Henning Bundgaard

Investigators

• Principal Investigator: Henning Bundgaard, MD, PhD, DMSc, Rigshospitalet Copenhagen University Hospital, Department of Cardiology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Henning Bundgaard, Consultant, dr. med., Rigshospitalet, Denmark
• ClinicalTrials.gov Identifier: NCT01876433
• Other Study ID Numbers: 2012-004805-29
• First Posted: Jun 12, 2013
• Last Update Posted: Oct 19, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Heart Failure; Mirabegron

Study Results

No Results Posted as of Oct 19, 2020