Beta 3 Agonist Treatment in Heart Failure

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) Clinical Trial

— Beat-HF  

Official title:

Beta 3 Agonist Treatment in Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01876433
• Other study ID #: 2012-004805-29
• Status: Completed
• Phase: Phase 2
• Start date: September 30, 2013
• Est. completion date: September 30, 2015

Study information

• Verified date: October 2020
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: September 30, 2015
• Est. primary completion date: September 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
• Heart Failure

Intervention

Drug:
• Mirabegron

• Placebo

Locations

Country	Name	City	State
Australia	Monash Center of Cardiovascular Research.	Melbourne
Australia	Department of Cardiology, Royal North Shore Hospital.	Sydney
Denmark	Department of Cardiology, The Heart Centre, Rigshospitalet Copenhagen University Hospital.	Copenhagen Ø

Sponsors (1)

Lead Sponsor	Collaborator
Henning Bundgaard

Countries where clinical trial is conducted

Australia,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in LVEF (measured by MRI or CT)		6 months
Secondary	A reduction in NT proBNP		6 months
Secondary	An increase in 6 min walking distance		6 months
Secondary	An increase in CO/SV		6 months
Secondary	A reduction in LVIDd		6 months
Secondary	An improvement in diastolic function		6 months
Secondary	A reduction in LA volume		6 months
Secondary	A reduction in LV diameters		6 months
Secondary	A shortening of the QT interval		6 months
Secondary	Improvement in quality of life		6 monhs
Secondary	Improvement in functional class		6 months