Heart Failure With Reduced Ejection Fraction NYHA Class III-IVPhase 2/3BEAT-HF IINCT03926754
Beta 3 Agonist Treatment in Heart Failure-2
A Phase 2/3 study testing Mirabegron in people with Heart Failure With Reduced Ejection Fraction NYHA Class III-IV, run by Henning Bundgaard at 1 site in Denmark.
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 moderate to severe chronic heart failure (LVEF<35%, NYHA III-IV). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction NYHA Class III-IV
- What is being tested?
- Mirabegron
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteDenmark
- Study dates
- 23 Jan 2017to 21 Jan 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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:
Read more
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.
- Being tested
- Mirabegron
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirabegronDrug
Also called 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).
| Study group | Role | What they receive |
|---|---|---|
| Mirabegron | Active comparator | Active treatment arm (mirabegron) Receives: Drug: Mirabegron |
| Placebo | Placebo comparator | Placebo Receives: Drug: Mirabegron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in left ventricular ejection fraction as measured by computed tomography
Study A
Measured: 3 months
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.
Measured: At 3 hours and at 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2019
- Study start23 Jan 2017
- Primary completion21 Jan 2021
- Study completion21 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection Fraction NYHA Class III-IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henning Bundgaard
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Bispebjerg and Frederiksberg, Hillerød hospital, Denmark, Herlev Hospital, Hvidovre University Hospital, Bornholm Hospital, Denmark, Royal North Shore Hospital
- Responsible party
- Sponsor-investigator, Henning Bundgaard, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03926754
- Sponsor's protocol ID
- 2016-002367-34
- Other IDs
- H-16030780, 2016
- Acronym
- BEAT-HF II
- Status last verified
- Apr 2022
- First submitted
- 4 Jul 2017
- Last updated
- 4 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Publications
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.
PubMed 27990717
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta 3 Agonist Treatment in Heart Failure-2
- ClinicalTrials.gov ID
- NCT03926754
- Acronym / sponsor ID
- BEAT-HF II / 2016-002367-34
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Henning BundgaardUniversity, hospital or other
- Collaborators
- University Hospital Bispebjerg and Frederiksberg, Hillerød hospital, Denmark, Herlev Hospital, Hvidovre University Hospital, Bornholm Hospital, Denmark, Royal North Shore Hospital
- Study start
- 23 Jan 2017 (actual)
- Primary completion
- 21 Jan 2021 (actual)
- Study completion
- 21 Jan 2021 (actual)
- First posted
- 24 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mirabegron | Active comparator | Drug: MirabegronActive treatment arm (mirabegron) |
| Placebo | Placebo comparator | Drug: MirabegronPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirabegronAlso: PlaceboStudy 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). | Drug | Mirabegron, Placebo |
Primary outcome
Increase in left ventricular ejection fraction as measured by computed tomography
Time frame: 3 months
Study A
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Background: PubMed 27990717Bundgaard 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.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Mirabegron in people with Heart Failure With Reduced Ejection Fraction NYHA Class III-IV, run by Henning Bundgaard at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increase in left ventricular ejection fraction as measured by computed tomography (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03926754, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2022.