NCT02599480

Assessment of Efficacy of Mirabegron, a New beta3-adrenergic Receptor in the Prevention of Heart Failure

A Multi-centre Randomized, Placebo-controlled Trial of Mirabegron, a New beta3-adrenergic Receptor Agonist on Left Ventricular Mass and Diastolic Function in Patients With Structural Heart Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 296 (actual)
• Sponsor: Jean-Luc Balligand · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Background Heart failure (HF) represents a major and growing public health burden. Patients with HF are classically divided into two groups: those with HF with preserved ejection fraction (HFpEF), and those with HF and reduced ejection fraction (HFrEF). As HF is a progressive disorder increasing with age, the proportion of these patients is rising due to the aging of the population. Beside costs, HFpEF also puts a heavy burden on the quality of life of (mostly elderly) patients, with a loss of autonomy and the dyscomfort of repeated hospitalisations. Therefore, HFpEF is a chronic, costly, debilitating disease. A major contributor to HFpEF is myocardial remodelling, e.g. hypertrophy and fibrosis, as well as cellular functional/structural modifications leading to alteration in contractile properties and ventricular distensibility. Unfortunately, there are currently no evidence-based treatment strategies. Study claim The proposed clinical trial will provide a proof of concept in humans for the clinical efficacy of a novel therapeutic concept: β3AR activation to attenuate/prevent cardiac remodeling. Recently, a new, specific agonist at human β3-AR (mirabegron) with higher benefit/risk balance was developed and marketed for clinical use in a non-cardiovascular disease (overactive bladder disease). The trial will test the drug repurposing of mirabegron for the prevention of cardiac remodeling leading to HFpEF. Using pre-clinical models, the investigators demonstrated that activation of β3AR attenuates myocardial hypertrophy and fibrosis in response to neurohormonal or hemodynamic stresses, without compromising LV function. Therefore, the recent availability of this new drug offers the possibility to test the potential benefit of mirabegron (vs placebo) as add-on therapy (on top of standard care) to prevent/delay myocardial remodelling in patients at high risk of developing HFpEF. Who can participate? Patients with structural cardiac disease with or without HF symptoms (max. NYHA 2). What does the study involve? Patients will be requested to go 5 times to the hospital to perform cardiac MRI (3X), echocardiography (3X), exercise tolerance test (2X), Pet scanning (2X) and blood sampling (4X). Who is the sponsor? The Université catholique de Louvain (UCL) is the academic sponsor and Prof. Jean-Luc Balligand is the principal coordinator of the study. Who is funding the study? Beta3\_LVH is an investigator-initiated project funded by a Horizon 2020 grant from the European Commission.

Conditions

• Hypertrophy, Left Ventricular

Interventions

Type	Name	Description
DRUG	mirabegron	50 mg daily during 12 months
PROCEDURE	Echocardiography	Echocardiography
PROCEDURE	Cardiac MRI	Cardiac MRI
PROCEDURE	Maximal exercise capacity	Maximal exercise capacity
PROCEDURE	Blood sampling	Blood sampling for study assessments and future exploratory studies.
PROCEDURE	Endothelial function measurement	EndoPAT assessment
RADIATION	18FDG-PET	PET scanning for beige/brown fat activation

Timeline

• Start date: 2016-09-12
• Primary completion: 2021-02-26
• Completion: 2022-02-16
• First posted: 2015-11-06
• Last updated: 2025-02-10

Locations

10 sites across 8 countries: Belgium, France, Germany, Greece, Italy, Poland, Portugal, United Kingdom