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Beta 3 Agonist Treatment in Heart Failure (Beat-HF)

Primary Purpose

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Mirabegron

Placebo

About this trial

This is an interventional treatment trial for Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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.

Sites / Locations

Monash Center of Cardiovascular Research.
Department of Cardiology, Royal North Shore Hospital.
Department of Cardiology, The Heart Centre, Rigshospitalet Copenhagen University Hospital.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Beta-3-agonist

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Increase in LVEF (measured by MRI or CT)

Secondary Outcome Measures

A reduction in NT proBNP

An increase in 6 min walking distance

An increase in CO/SV

A reduction in LVIDd

An improvement in diastolic function

A reduction in LA volume

A reduction in LV diameters

A shortening of the QT interval

Improvement in quality of life

Improvement in functional class

Full Information

NCT ID

NCT01876433

First Posted

June 10, 2013

Last Updated

October 14, 2020

Sponsor

Henning Bundgaard

1. Study Identification

Unique Protocol Identification Number

NCT01876433

Brief Title

Beta 3 Agonist Treatment in Heart Failure

Acronym

Beat-HF

Official Title

Beta 3 Agonist Treatment in Heart Failure

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

September 30, 2013 (Actual)

Primary Completion Date

September 30, 2015 (Actual)

Study Completion Date

September 30, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Henning Bundgaard

4. Oversight

Data Monitoring Committee

Yes

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Beta-3-agonist

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Mirabegron

Other Intervention Name(s)

Beta 3 agonist

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Increase in LVEF (measured by MRI or CT)

Time Frame

6 months

Secondary Outcome Measure Information:

Title

A reduction in NT proBNP

Time Frame

6 months

Title

An increase in 6 min walking distance

Time Frame

6 months

Title

An increase in CO/SV

Time Frame

6 months

Title

A reduction in LVIDd

Time Frame

6 months

Title

An improvement in diastolic function

Time Frame

6 months

Title

A reduction in LA volume

Time Frame

6 months

Title

A reduction in LV diameters

Time Frame

6 months

Title

A shortening of the QT interval

Time Frame

6 months

Title

Improvement in quality of life

Time Frame

6 monhs

Title

Improvement in functional class

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Henning Bundgaard, MD, PhD, DMSc

Organizational Affiliation

Rigshospitalet Copenhagen University Hospital, Department of Cardiology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Monash Center of Cardiovascular Research.

City

Melbourne

Country

Australia

Facility Name

Department of Cardiology, Royal North Shore Hospital.

City

Sydney

Country

Australia

Facility Name

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

City

Copenhagen Ø

ZIP/Postal Code

2100

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

27990717

Citation

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.

Results Reference

derived

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Beta 3 Agonist Treatment in Heart Failure

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