NCT02599480

Brief Summary

This study will assess the efficacy of mirabegron, a new beta3-adrenergic receptor in the prevention of heart failure. This is a two armed, prospective, randomized, placebo-controlled, multi-centric european phase IIb trial with placebo and mirabegron distributed in a 1:1 fashion. The patients enrolled will have cardiac structural remodeling with or without symptoms of heart failure (maximum NYHA II). Patients will be monitored for change in left ventricular mass (assessed by cardiac MRI) and/or changes in diastolic function (assessed by echocardiography) after 12 months of treatment.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
296

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2016

Longer than P75 for phase_2

Geographic Reach
8 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 30, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 6, 2015

Completed
10 months until next milestone

Study Start

First participant enrolled

September 12, 2016

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 26, 2021

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 16, 2022

Completed
Last Updated

February 10, 2025

Status Verified

February 1, 2025

Enrollment Period

4.5 years

First QC Date

October 30, 2015

Last Update Submit

February 5, 2025

Conditions

Hypertrophy, Left Ventricular

Keywords

HFpEFleft ventricular hypertrophycardiac remodeling,

Outcome Measures

Primary Outcomes (2)

  • Change in left ventricular mass index (LVMI)

    Change in left ventricular mass index (LVMI in g/m2, defined as left ventricular mass divided by body surface) measured at baseline and 12 months after randomisation.

    12 months

  • Change in diastolic function

    Change in diastolic function, assessed as the ratio of peak early transmitral ventricular filling velocity to early diastolic tissue Doppler velocity (E/e') measured at baseline and 12 months after randomisation.

    12 months

Secondary Outcomes (8)

  • Cardiac fibrosis

    12 months

  • Left atrial volume index

    12 months

  • LV mass index (by cardiac MRI)

    6 months

  • Diastolic function (E/e')

    6 months

  • serum biomarkers

    3, 6, 12 months

  • +3 more secondary outcomes

Study Arms (2)

mirabegron

ACTIVE COMPARATOR

Patients will be orally administererd with 50 mg of mirabegron once a day during 12 months.

Drug: mirabegronProcedure: EchocardiographyProcedure: Cardiac MRIProcedure: Maximal exercise capacityProcedure: Blood samplingProcedure: Endothelial function measurementRadiation: 18FDG-PET

Placebo

PLACEBO COMPARATOR

Patients will be orally administererd with a placebo once a day during 12 months.

Procedure: EchocardiographyProcedure: Cardiac MRIProcedure: Maximal exercise capacityProcedure: Blood samplingProcedure: Endothelial function measurementRadiation: 18FDG-PET

Interventions

mirabegronDRUG

50 mg daily during 12 months

Also known as: Betmiga, Myrbetriq
mirabegron
EchocardiographyPROCEDURE

Echocardiography

Placebomirabegron
Cardiac MRIPROCEDURE

Cardiac MRI

Placebomirabegron
Maximal exercise capacityPROCEDURE

Maximal exercise capacity

Placebomirabegron
Blood samplingPROCEDURE

Blood sampling for study assessments and future exploratory studies.

Placebomirabegron
Endothelial function measurementPROCEDURE

EndoPAT assessment

Placebomirabegron
18FDG-PETRADIATION

PET scanning for beige/brown fat activation

Placebomirabegron

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age between 18 and 90 years
  • Morphological signs of structural cardiac remodelling by echocardiography, i.e. increased LV mass index (110 g/m2 or higher for female; 134 g/m2 or higher for male subjects (Devereux, Reichek 1977)) or end-diastolic wall thickness \> or equal to 13 mm in at least one wall segment
  • Patients may have atrial fibrillation (AF), but with well-regulated ventricular response, i.e. heart rate\<100/min (RACE II - (Groenveld et al. 2013, 2013)),
  • Written informed consent
  • For subjects unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the subject has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the subject.

You may not qualify if:

  • Unstable hypertension with systolic BP≥160 mm Hg and/or diastolic BP≥100 mm Hg (based on office measurement, not ambulatory measurement)
  • Documented ischemic cardiac disease
  • History of hospitalization for overt heart failure within last 12 months
  • Patients after heart transplantation
  • Genetic hypertrophic or dilated cardiomyopathy
  • Dysthyroidism.
  • Severe valvulopathy
  • NYHA-class \> II
  • BMI \>40 kg/m2
  • EF \< 50%, regardless of symptoms
  • eGFR \< 30 ml/min (by MDRD formula)
  • Abnormal liver function tests
  • Type I diabetes, complicated type II diabetes
  • Patients with anemia
  • Patients with bladder outlet obstruction
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Nantes university hospital (CHU Nantes)

Nantes, 44000, France

Location

Center for Cardiovascular Research Berlin (CCR/Charité)

Berlin, 10115, Germany

Location

University Medical Center Göttingen (UMG-GOE)

Göttingen, 37099, Germany

Location

University of Leipzig

Leipzig, Germany

Location

Athens University Medical School (NKUA)

Athens, 115 27, Greece

Location

Hospital "Papa Giovanni XXIII" (HPG23)

Bergamo, 1 - 24127, Italy

Location

Department of Heart Diseases at Wroclaw Medical University (UMW)

Wroclaw, 50-981, Poland

Location

Association for Research and Development of the Faculty of Medicine (AIDFM)

Lisbon, 1649-028, Portugal

Location

University of Oxford - Division of Cardiovascular Medicine (UOXF)

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (5)

  • Belge C, Hammond J, Dubois-Deruy E, Manoury B, Hamelet J, Beauloye C, Markl A, Pouleur AC, Bertrand L, Esfahani H, Jnaoui K, Gotz KR, Nikolaev VO, Vanderper A, Herijgers P, Lobysheva I, Iaccarino G, Hilfiker-Kleiner D, Tavernier G, Langin D, Dessy C, Balligand JL. Enhanced expression of beta3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase. Circulation. 2014 Jan 28;129(4):451-62. doi: 10.1161/CIRCULATIONAHA.113.004940. Epub 2013 Nov 4.

    PMID: 24190960BACKGROUND

  • Balligand JL. beta(3)-Adrenoceptor stimulation on top of beta(1)-adrenoceptor blockade "Stop or Encore?". J Am Coll Cardiol. 2009 Apr 28;53(17):1539-42. doi: 10.1016/j.jacc.2009.01.048. No abstract available.

    PMID: 19389565BACKGROUND

  • Dessy C, Balligand JL. Beta3-adrenergic receptors in cardiac and vascular tissues emerging concepts and therapeutic perspectives. Adv Pharmacol. 2010;59:135-63. doi: 10.1016/S1054-3589(10)59005-7.

    PMID: 20933201BACKGROUND

  • Menghoum N, Badii MC, Leroy M, Parra M, Roy C, Lejeune S, Vancraeynest D, Pasquet A, Brito D, Casadei B, Depoix C, Filippatos G, Gruson D, Edelmann F, Ferreira VM, Lhommel R, Mahmod M, Neubauer S, Persu A, Piechnik S, Hellenkamp K, Ikonomidis I, Krakowiak B, Pieske B, Pieske-Kraigher E, Pinto F, Ponikowski P, Senni M, Trochu JN, Van Overstraeten N, Wachter R, Gerber BL, Balligand JL, Beauloye C, Pouleur AC. Exploring the impact of metabolic comorbidities on epicardial adipose tissue in heart failure with preserved ejection fraction. Cardiovasc Diabetol. 2025 Mar 22;24(1):134. doi: 10.1186/s12933-025-02688-7.

    PMID: 40121452DERIVED

  • Balligand JL, Brito D, Brosteanu O, Casadei B, Depoix C, Edelmann F, Ferreira V, Filippatos G, Gerber B, Gruson D, Hasenclever D, Hellenkamp K, Ikonomidis I, Krakowiak B, Lhommel R, Mahmod M, Neubauer S, Persu A, Piechnik S, Pieske B, Pieske-Kraigher E, Pinto F, Ponikowski P, Senni M, Trochu JN, Van Overstraeten N, Wachter R, Pouleur AC. Repurposing the beta3-Adrenergic Receptor Agonist Mirabegron in Patients With Structural Cardiac Disease: The Beta3-LVH Phase 2b Randomized Clinical Trial. JAMA Cardiol. 2023 Nov 1;8(11):1031-1040. doi: 10.1001/jamacardio.2023.3003.

    PMID: 37728907DERIVED

MeSH Terms

Conditions

Hypertrophy, Left Ventricular

Interventions

mirabegronBlood Specimen Collection

Condition Hierarchy (Ancestors)

CardiomegalyHeart DiseasesCardiovascular DiseasesHypertrophyPathological Conditions, AnatomicalPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Jean-Luc Balligand, Prof. MD

    Université Catholique de Louvain

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

October 30, 2015

First Posted

November 6, 2015

Study Start

September 12, 2016

Primary Completion

February 26, 2021

Study Completion

February 16, 2022

Last Updated

February 10, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will share

Individual participant data required to reach aims in an approved proposal, after de-identification, will be made available to investigators whose proposed use of the data has been approved by the study's Executive Committee. Proposals may be submitted up to 36 months after publication of the study results and should be directed to Jean-Luc.Balligand@uclouvain.be.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
up to 36 months after publication of the study results
Access Criteria
Upon approval by the study Steering Committee of a valid proposal by requesters

Locations

BE(1)IT(1)GR(1)DE(3)GB(1)FR(1)PL(1)PT(1)