Assessment of efficacy of mirabegron, a new beta3-adrenergic receptor in the prevention of heart failure

Phase 2

Completed

• Conditions: Structural heart disease (hypertrophic cardiac remodeling, stage B AHA) at high risk for developing HFpEF (heart failure with preserved ejection fraction).; Circulatory System

• Registration Number: ISRCTN65055502
• Lead Sponsor: niversité catholique de Louvain (Belgium)

Brief Summary

2018 Protocol article in https://pubmed.ncbi.nlm.nih.gov/29932311/ protocol (added 05/06/2020) 2023 Results article in https://doi.org/10.1001/jamacardio.2023.3003 (added 06/10/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-10-30
• Study Completion: 2022-09-01
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 296

Inclusion Criteria

1. Age between 18 and 90 years
2. Arterial hypertension on stable therapy according to current guideline algorithms (including stable medication for at least four weeks before inclusion)
3. 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
4. Patients may have atrial fibrillation (AF), but with well-regulated ventricular response, i.e. heart rate<100/min at inclusion (RACE II - (Groenveld et al. 2013, 2013))
5. Written informed consent
6. 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

1. Unstable hypertension with systolic BP=160 mm Hg and/or diastolic BP=100 mm Hg (confirmed at three consecutive office measurements in sitting position); if so, the patient may be re-screened after optimization of anti-hypertensive treatment, which should be stabilized for at least four weeks before inclusion.
2. Documented ischemic cardiac disease:
2.1. current angina pectoris or
2.2. ischemia on stress test or
2.3. untreated coronary stenosis >50% or
2.4. history of acute myocardial infarction (AMI) or
2.5. coronary artery bypass graft (CABG, < than 3 months prior to screening) or
2.6. percutaneous transluminal coronary angioplasty (PTCA) less than 3 months prior to screening.
3. History of hospitalization for overt heart failure within last 12 months
4. Patients after heart transplantation
5. Genetic hypertrophic or dilated cardiomyopathy
6. Dysthyroidism.
7. Severe valvulopathy (less than 1 cm2 aortic valve area or major mitral valve insufficiency at Doppler echocardiography)
8. NYHA-class > II
9. BMI > 40 kg/m2
10. EF < 50%, regardless of symptoms
11. 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
12. eGFR < 30 ml/min
13. Abnormal liver function tests (AST or ALT >2 X upper normal limit or GGT>3x upper normal limit)
14. Type I diabetes, complicated type II diabetes (i.e. with documented coronary macroangiopathy , cfr exclusion criterion 1 or documented other vascular complication)
15. Patients with anemia (male: Hb <130 g/l, female: Hb <120 g/l)
16. Patients with bladder outlet obstruction
17. Patients using antimuscarinic cholinergic drugs for treatment of OAB
18. Current use of digitalis, bupranolol, propranolol, nebivolol (known to interfere with ß3AR signalling)*
19. Patients continuously treated with Sildenafil or other PDE5 inhibitors
20. Current use of antifungal azole derivatives (fluconazole, itraconazole, miconazole, posaconazole, voriconazole) (known inhibitors of CYP3A4, the main metabolizer of mirabegron)
21. Current treatment with mirabegron or indication for future treatment with mirabegron due to other indications
22. Contraindication for MRI (e.g. pacemaker, defibrillator, ferromagnetic devices or severe claustrophobia)
23. Pregnant or nursing women
24. Participation in any other interventional trial
25. 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)
26. Contraindication to mirabegron (e.g. hypersensitivity) or any other components of the trial medication

* Note: patients are allowed

Study & Design

• Study Type: Interventional
• Study Design: Not specified