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

April 28, 2022 updated by: Henning Bundgaard

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

  1. Determine safety of administration of Mirabegron to patients with moderate to severe heart failure.
  2. 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).
  3. 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.
  4. Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with moderate to severe heart failure.
  5. Determine effects of Mirabegron on circulating biomarkers in patients with moderate to severe heart failure.
  6. Determine the immediate and short term haemodynamic effects of Mirabron as measured by CT and invasively.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Copenhagen, Denmark, 2100
        • Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Stable heart failure NYHA class III-IV on ischemic or non-ischemic basis
  2. Left ventricular ejection fraction (LVEF) < 35% as assessed by cardiac CT
  3. NT proBNP > 1000 pg/ml
  4. 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.
  5. No change in diuretics ≤1 week
  6. No admittances to hospital for treatment with intravenously administered positive inotropic agents ≤ 4 weeks.
  7. >18 years

Exclusion Criteria:

  1. Acute myocardial infarction (AMI) or revascularisation < 3 month ago
  2. Uncorrected significant primary obstructive valve disease
  3. Planned major surgery including cardiac revascularisation
  4. Hemodynamically significant obstructive cardiomyopathy
  5. Acute myocarditis or constrictive pericarditis
  6. Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR< 30 ml/min/1,73 m2) diseases
  7. Heart failure due to uncorrected thyroid disease
  8. Cardiac mechanical support
  9. < 6 months after CRT
  10. 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)
  11. Unable to give informed consent
  12. Reduced compliance
  13. All women of child bearing potential will be required to use adequate contraception
  14. Pregnant or lactating women
  15. Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin.
  16. Known allergy to iodine containing contrast
  17. Estimated GFR < 30 ml/min/1.73 m2
  18. Congenital or drug induced QT prolongation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo

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).

Other Names:
  • Placebo
Active Comparator: Mirabegron
Active treatment arm (mirabegron)

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).

Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase in left ventricular ejection fraction as measured by computed tomography
Time Frame: 3 months
Study A
3 months
Change in invasive hemodynamics assesses by right heart catherization
Time Frame: At 3 hours and at 1 week
Study B is explorative assessing the effect on invasive parameters including cardiac output, pulmonary wedge pressure and pulmonary and systemic vascular resistance.
At 3 hours and at 1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2017

Primary Completion (Actual)

January 21, 2021

Study Completion (Actual)

January 21, 2021

Study Registration Dates

First Submitted

July 4, 2017

First Submitted That Met QC Criteria

April 23, 2019

First Posted (Actual)

April 24, 2019

Study Record Updates

Last Update Posted (Actual)

May 4, 2022

Last Update Submitted That Met QC Criteria

April 28, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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