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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 October 2021
• Main ID: NCT02599480
• Date of registration: 30/10/2015
• Prospective Registration: Yes
• Primary sponsor: Jean-Luc Balligand
• Public title: Assessment of Efficacy of Mirabegron, a New beta3-adrenergic Receptor in the Prevention of Heart Failure Beta3_LVH
• Scientific title: 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
• Date of first enrolment: April 2016
• Target sample size: 296
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02599480
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belgium, France, Germany, Greece, Italy, Poland, Portugal, United Kingdom

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age between 18 and 90 years

- Arterial hypertension on stable therapy according to current guideline algorithms
(including stable medication for at least four weeks before inclusion),

- 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 >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.

Exclusion Criteria:

- 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

- Known other cause (i.e. COPD) of respiratory dysfunction; patients under positive
pressure (CPAP) treatment for sleep apnea syndrome may be included, provided they have
been under regular treatment for at least one year before inclusion in the study

- 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

- Patients using antimuscarinic cholinergic drugs for treatment of OAB

- Current use of digitalis, bupranolol, propranolol, nebivolol

- Patients continuously treated with Sildenafil or other PDE5 inhibitors.

- Current use of antifungal azole derivatives (fluconazole, itraconazole, miconazole,
posaconazole, voriconazole)

- Current treatment with mirabegron or indication for future treatment with mirabegron
due to other indications

- Contraindication for MRI

- Pregnant or nursing women

- Participation in any other interventional trial

- Fertile women (within two years of their last menstruation) without appropriate
contraceptive measures (hormonal implant, injections, oral contraceptives,
intrauterine devices, partner with vasectomy) while participating in the trial
(participants using a hormone-based method have to be informed of possible effects
from the trial medication on contraception)

- Contraindication to mirabegron (e.g. hypersensitivity) or any other components of the
trial medication



Age minimum: 18 Years
Age maximum: 90 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypertrophy, Left Ventricular

Intervention(s)

Radiation: 18FDG-PET

Procedure: Cardiac MRI

Procedure: Endothelial function measurement

Procedure: Maximal exercise capacity

Drug: mirabegron

Procedure: Blood sampling

Procedure: Echocardiography

Primary Outcome(s)

Change in left ventricular mass index (LVMI) [Time Frame: 12 months]

Change in diastolic function [Time Frame: 12 months]

Secondary Outcome(s)

Left atrial volume index [Time Frame: 12 months]

Maximal exercise capacity [Time Frame: 12 months]

Diastolic function (E/e') [Time Frame: 6 months]

Cardiac fibrosis [Time Frame: 12 months]

Emergence of treatment-related adverse events [Time Frame: 12 months]

metabolic parameters [Time Frame: 3, 6, 12 months]

serum biomarkers [Time Frame: 3, 6, 12 months]

LV mass index (by cardiac MRI) [Time Frame: 6 months]

Secondary ID(s)

Beta3_LVH V1.0

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

European Commission

Nantes University Hospital

European Clinical Research Infrastructure Network

Center for Cardiovascular Research Berlin

Northern Lisbon Hospital Center

University of Athens

Papa Giovanni XXIII Hospital

Wroclaw Medical University

University Medical Center Goettingen

Zentrum für Klinische Studien Leipzig

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

European Society of Cardiology

University of Oxford