Beta 3 Agonist Treatment in Heart Failure | NCT01876433

Studies
Beta 3 Agonist Treatment in Heart Failure

NCT01876433

Sponsor

Henning Bundgaard

Status

Completed

Last Update Posted

Oct 19, 2020Actual

Enrollment

70Actual

Phase

Phase 2

Conditions

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Interventions

Mirabegron
Placebo

Countries

Australia
Denmark

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Oct 2020

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Sep 30, 2013Actual

Primary Completion Date

Sep 30, 2015Actual

Completion Date

Sep 30, 2015Actual

First Submitted Date

Jun 10, 2013

First Submission Date that Met QC Criteria

Jun 11, 2013

First Posted Date

Jun 12, 2013Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 14, 2020

Last Update Posted Date

Oct 19, 2020Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Detailed Description

Not provided

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

70Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Beta-3-agonist	Active Comparator	Mirabegron 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.	Drug: Mirabegron
Placebo	Placebo Comparator	Placebo 25 mg x 2 titrated up to maximal tolerated dosis or a maximum of 150 mg x 2.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Mirabegron	Drug		Beta-3-agonist	Beta 3 agonist
Placebo

Measure	Description	Time Frame
Increase in LVEF (measured by MRI or CT)		6 months

Measure	Description	Time Frame
A reduction in NT proBNP		6 months
An increase in 6 min walking distance		6 months
An increase in CO/SV

Eligibility Module

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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Name	Affiliation	Role
Henning Bundgaard, MD, PhD, DMSc	Rigshospitalet Copenhagen University Hospital, Department of Cardiology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Monash Center of Cardiovascular Research.		Melbourne			Australia
Department of Cardiology, Royal North Shore Hospital.

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38452283	Derived	Bahrami HSZ, Hasselbalch RB, Soholm H, Thomsen JH, Sorgaard M, Kofoed KF, Valeur N, Boesgaard S, Fry NAS, Moller JE, Raja AA, Kober L, Iversen K, Rasmussen H, Bundgaard H. First-In-Man Trial of beta3-Adrenoceptor Agonist Treatment in Chronic Heart Failure: Impact on Diastolic Function. J Cardiovasc Pharmacol. 2024 May 1;83(5):466-473. doi: 10.1097/FJC.0000000000001545.
27990717

ID	Term
C520025	mirabegron
D058667	Adrenergic beta-3 Receptor Agonists

ID	Term
D000318	Adrenergic beta-Agonists
D000322	Adrenergic Agonists
D018663	Adrenergic Agents
D018377	Neurotransmitter Agents