Heart Failure MedDRA version: 19.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Mirabegron "Betmiga" 50 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Mirabegron
CAS Number: 223673-61-8
Other descriptive name: MIRABEGRON
Concentration unit: mg milligram(s)
Concen
Sponsors
Hjertemedicinsk klinik, Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Stable heart failure NYHA class II-III on ischemic or non-ischemic basis 2. Left ventricular ejection fraction (LVEF) 4 weeks with no current plan for changing HF therapy. The therapy must include a beta-blocker. 5. No change in diuretics 18 years 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Acute myocardial infarction (AMI) or revascularisation < 3 month ago 2. Atrial fibrillation (for technical reasons in relation to imaging and HR reporting) 3. Uncorrected significant primary obstructive valve disease 4. Planned major surgery including cardiac revascularisation 5. Hemodynamically significant obstructive cardiomyopathy 6. Acute myocarditis or constrictive pericarditis 7. Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR< 40 ml/min/1,73 m2) diseases 8. Heart failure due to uncorrected thyroid disease 9. Cardiac mechanical support 10. < 6 months after CRT 11. Uncontrolled hypotension (defined as symptomatic systolic blood pressure < 90 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below) 12. Unable to give informed consent 13. Reduced compliance 14. All women of child bearing potential will be required to use adequate contraception 15. Pregnant or lactating women 16. Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin (only applies to Study A). For exclusion from the CT part of the study - Known allergy to iodine containing contrast - Estimated GFR < 40 ml/min/1.73 m2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to assess the effects of Mirabegron on left ventricular systolic function in patients with moderate to severe chronic heart failure. ;Secondary Objective: In patients with moderate to severe heart failure: 1. Determine safety of administration of Mirabegron. 2. Determine if treatment with Mirabegron for 6 months induces beneficial cardiac structural remodeling. 3. Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test. 4. Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias. 5. Determine effects of Mirabegron on circulating biomarkers. 6. Determine the immediate haemodynamic effects of Mirabron as measured invasively. ;Primary end point(s): Increase in LVEF (measured by CT) -For acute study - Study B: • Changes in pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) at the submaximal exercise intensity of 50 % of the maximal exercise capacity ;Timepoint(s) of evaluation of this end point: After 6 months For acute study B: After 2.5 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: After 6 months For acute study B: After 2.5 hours;Secondary end point(s): 1) A reduction in NT proBNP, 2) A reduction in Troponin I and troponin T, 3) An increase in 6 min walking distance, 4) Reduced admissions to hospital 5) A reduced requirement for diuretics 6) An increase in CO/SV, 7) A reduction in LV diameters, 8) An improvement in diastolic function, 9) A reduction in LA volume, 10) A shortening of the QT interval 11) Improvement in functional class For acute study - Study B: • Cardiac index (CI) during submaximal exercise before and after Mirabegron administration • Pulmonary and systemic vascular resistance during exercise • Left ventricular end diastolic diameter during exercise • The change in mPAP (mean pulmonary artery pressure) from rest to submaximal exercise • The change in BNP, MR-ANP and copeptin from rest to submaximal exercise | — |
Countries
Denmark
Contacts
Public ContactHenning Bundgaard
Hjertemedicinsk afdeling, Rigshospitalet
Outcome results
None listed