A multi-centre placebo-controlled clinical trial, to show, if treatment with the drug tested (mirabegron, trade name of the finished medication: Betmiga®)????? prevents/delays myocardial remodeling (thickening of the myocardial wall) in patients at high risk of developing diastolic heart failure (heart failure with preserved ejection fraction/HFpEF) due to their underlying structural heart disease.??????
- Conditions
- Structural heart disease at high risk for progressive hypertrophic cardiac remodeling at risk of developing HFpEF (heart failure with preserved ejection fraction).MedDRA version: 20.0Level: LLTClassification code 10019290Term: Heart insufficiencySystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2015-003146-75-DE
- Lead Sponsor
- niversité catholique de Louvain (UCL)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 296
••Age between 18 and 90 years
•Morphological signs of structural cardiac remodelling by echocardiography, i.e. increased LV mass index (=95 g/m2 or higher for female; =115 g/m2 or higher for male subjects (Ponikowski et al 2016)) or end-diastolic wall thickness >=13 mm in at least one wall segment
•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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 176
•Unstable arterial 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
•Hypertensive patients not under stable therapy according to current guideline algorithm (Mancia et al. 2013) (including stable medication for at least 4 weeks before inclusion)
•Documented ischemic cardiac disease:
ocurrent angina pectoris or
oischemia on stress test or
ountreated coronary stenosis >50% or
ohistory of acute myocardial infarction (AMI) or
ocoronary artery bypass graft (CABG, < than 3 months prior to screening) or
opercutaneous transluminal coronary angioplasty (PTCA) less than 3 months prior to screening.
•Patients with uncontrolled recurrent persistent and permanent atrial fibrillation (AF) according to AHA/ACC/ESC guidelines (Dixon et al. 2005) (with a heart rate > 100/min, RACE II - (Groenveld et al. 2013, 2013)). If AF with HR>100/min, the patient may be rescreened after treatment for rate control.
•History of hospitalization for overt heart failure within last 12 months
•History of high degree impulse conduction blocks (> 2nd degree AV block type 2)
•Patients after heart transplantation
•Genetic hypertrophic or dilated cardiomyopathy
•Dysthyroidism
•Severe valvulopathy (less than 1 cm2 aortic valve area, mitral insufficiency of severe grade at Doppler echo)
•Congenital valvulopathies
•Patients with a known history of QT prolongation (> 450 ms) (CHMP/ICH, 2005) or patients with documented QT prolongation (>450 ms) while taking medicinal products known to prolong the QT interval
•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 efficiently controlled by CPAP for at least one year before inclusion in the study
•Moderate renal impairment defined as eGFR < 30 ml/min
•Abnormal liver function tests (AST or ALT >2 X upper normal limit or patients with known hepatic impairment defined as Child-Pugh class B or higher)
•Type I diabetes, complicated type II diabetes (i.e. with documented coronary macroangiopathy , cfr exclusion criterion 1 or documented other vascular complication) (National Diabetes Education Initiative - NDEI).
•Patients with anaemia (male: Hb <130 g/l, female: Hb <120 g/l)
•Patients with bladder outlet obstruction
•Patients using antimuscarinic cholinergic drugs for treatment of OAB
•Current use of digitalis, bupranolol, propranolol, nebivolol (known to interfere with ß3AR signalling)
Note: patients are allowed to take a ß(1-2)-blocker, other than the drugs listed above (for explanation, see chapter 5.4.5).
•Patients continuously treated with Sildenafil or other PDE5 inhibitors.
•Current use of antifungal azole derivatives (fluconazole, itraconazole, miconazole, posaconazole, voriconazole) (known inhibitors of CYP3A4, the main metabolizer of mirabegron)
•Current treatment with mirabegron or indication for future treatment with mirabegron due to other indications
•Contraindication for MRI (e.g. defibrillator, ferromagnetic devices or severe claustrophobia, pacemaker - the latter only, if MRI is contraindicated)
•Pregnant or nursing women
•Women of child bearing potential without highly effective contraceptive mea
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method