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Beta 3 Agonist Treatment in Heart Failure-2 (BEAT-HF II)

Primary Purpose

Heart Failure With Reduced Ejection Fraction NYHA Class III-IV

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

Mirabegron

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction NYHA Class III-IV

Eligibility Criteria

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

Inclusion Criteria:

Stable heart failure NYHA class III-IV on ischemic or non-ischemic basis
Left ventricular ejection fraction (LVEF) < 35% as assessed by cardiac CT
NT proBNP > 1000 pg/ml
On optimised evidence-based pharmacological HF treatment stable ≥2 weeks with no current plan for changing HF therapy. The therapy must include a beta-blocker.
No change in diuretics ≤1 week
No admittances to hospital for treatment with intravenously administered positive inotropic agents ≤ 4 weeks.
>18 years

Exclusion Criteria:

Acute myocardial infarction (AMI) or revascularisation < 3 month ago
Uncorrected significant primary obstructive valve disease
Planned major surgery including cardiac revascularisation
Hemodynamically significant obstructive cardiomyopathy
Acute myocarditis or constrictive pericarditis
Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR< 30 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 < 80 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below)
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.
Known allergy to iodine containing contrast
Estimated GFR < 30 ml/min/1.73 m2
Congenital or drug induced QT prolongation

Sites / Locations

Rigshospitalet

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Mirabegron

Placebo

Arm Description

Active treatment arm (mirabegron)

Placebo

Outcomes

Primary Outcome Measures

Increase in left ventricular ejection fraction as measured by computed tomography

Study A

Change in invasive hemodynamics assesses by right heart catherization

Study B is explorative assessing the effect on invasive parameters including cardiac output, pulmonary wedge pressure and pulmonary and systemic vascular resistance.

Secondary Outcome Measures

Full Information

NCT ID

NCT03926754

First Posted

July 4, 2017

Last Updated

April 28, 2022

Sponsor

Henning Bundgaard

Collaborators

Bispebjerg-Frederiksberg Hospital, Denmark, Hillerød hospital, Denmark, Herlev Hospital, Hvidovre University Hospital, Bornholm Hospital, Denmark, Royal North Shore Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03926754

Brief Title

Beta 3 Agonist Treatment in Heart Failure-2

Acronym

BEAT-HF II

Official Title

Beta 3 Agonist Treatment in Heart Failure-2

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

January 23, 2017 (Actual)

Primary Completion Date

January 21, 2021 (Actual)

Study Completion Date

January 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Henning Bundgaard

Collaborators

Bispebjerg-Frederiksberg Hospital, Denmark, Hillerød hospital, Denmark, Herlev Hospital, Hvidovre University Hospital, Bornholm Hospital, Denmark, Royal North Shore Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

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 moderate to severe chronic heart failure (LVEF<35%, NYHA III-IV). The study is a randomized, placebo-controlled, double-blinded trial in two phases with two hypotheses: Chronic study - study A: Long-term treatment (3 months) with the β3 adrenergic receptor agonist Mirabegron is beneficial in patients with moderate to severe human heart failure Invasive study - Study B: Administration of Mirabegron in patients with heart failure leads to an immediate increase in cardiac output at a constant or reduced left ventricular filling pressure during submaximal exercise Specific aims Determine safety of administration of Mirabegron to patients with moderate to severe heart failure. Determine if treatment with Mirabegron for 3 months induces beneficial cardiac structural remodelling in patients with moderate to severe heart failure. In an open-label follow-up to determine the effects of Mirabegron after an extended duration (a total of 12 months). Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test in patients with moderate to severe heart failure. Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with moderate to severe heart failure. Determine effects of Mirabegron on circulating biomarkers in patients with moderate to severe heart failure. Determine the immediate and short term haemodynamic effects of Mirabron as measured by CT and invasively.

6. Conditions and Keywords

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

Heart Failure With Reduced Ejection Fraction NYHA Class III-IV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mirabegron

Arm Type

Active Comparator

Arm Description

Active treatment arm (mirabegron)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Mirabegron

Other Intervention Name(s)

Placebo

Intervention Description

Study A The maximum tolerated dose up to a maximum of 300 mg per day for 26 weeks. Study B One single dose of 300 mg at day one followed by 150 mg x 2 for 1 week (8-11 days).

Primary Outcome Measure Information:

Title

Increase in left ventricular ejection fraction as measured by computed tomography

Description

Study A

Time Frame

3 months

Title

Change in invasive hemodynamics assesses by right heart catherization

Description

Study B is explorative assessing the effect on invasive parameters including cardiac output, pulmonary wedge pressure and pulmonary and systemic vascular resistance.

Time Frame

At 3 hours and at 1 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Stable heart failure NYHA class III-IV on ischemic or non-ischemic basis Left ventricular ejection fraction (LVEF) < 35% as assessed by cardiac CT NT proBNP > 1000 pg/ml On optimised evidence-based pharmacological HF treatment stable ≥2 weeks with no current plan for changing HF therapy. The therapy must include a beta-blocker. No change in diuretics ≤1 week No admittances to hospital for treatment with intravenously administered positive inotropic agents ≤ 4 weeks. >18 years Exclusion Criteria: Acute myocardial infarction (AMI) or revascularisation < 3 month ago Uncorrected significant primary obstructive valve disease Planned major surgery including cardiac revascularisation Hemodynamically significant obstructive cardiomyopathy Acute myocarditis or constrictive pericarditis Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR< 30 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 < 80 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below) 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. Known allergy to iodine containing contrast Estimated GFR < 30 ml/min/1.73 m2 Congenital or drug induced QT prolongation

Facility Information:

Facility Name

Rigshospitalet

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Because of the sensitive nature of the data collected for this study, requests to access the dataset from qualified researchers trained in human subject confidentiality protocols may be sent to the principal investigator.

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

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Beta 3 Agonist Treatment in Heart Failure-2

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