ß3 adrenergic agoniSt Treatment in Chronic Pulmonary HypERtEnsion Secondary to heart failure

Phase 1

• Conditions: Pulmonary Hypertension secondary to heart failure; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-002949-32-ES
• Lead Sponsor: Fundació Clínic per la recerca Biomédica

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-17
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Written inform consent;
• =18 years-old;
• HF with reduced, intermediate or preserved ejection fraction, according to the definition of the European Society of Heart Failure guidelines.
• Significant PH combined postcapillary and precapillary PH determined by RHC showing the following:
Pulmonary artery wedge pressure or enddiastolic LV pressure =15 mmHg;
- Mean PAP=25 mmHg and:
.PVR=3 UW and/or diastolic gradient=7 mmHg or transpulmonary gradient=12mmHg.
• NYHA functional class II-III;
• On optimized evidence-based pharmacological treatment;
• Stable clinical condition defined as no changes in therapeutic regimen or hospitalization in the 30 days preceding recruitment and no current plan for changing therapy.
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

• Non-coronary cardiac surgery within the 12 months preceding recruitment performed or scheduled;
• Myocardial infarction or coronary revascularization in the last 3 months.
• Resynchronization therapy implanted in the last 6 months.
• Sinusal tachycardia or uncontrolled atrial fibrillation (HR>100 bpm);
• Uncontrolled systemic hypertension or symptomatic hypotension.
• Infiltrative cardiomyopathy.
• Premenopausal women with childbearing potential.
• Expected survival <1 year due to a disease other than HF;
• Severe renal failure (GFR <30 mL/min/1.73 m2 or hemodialysis);
• Severe hepatic impairment (transaminases >3 upper limit of normality);
• cQT interval on the ECG >430 ms in male or >450 ms in female;
• Concomitant use of specific pulmonary vasodilators (sildenafil, bosentan, macitentan, riociguat and other endothelin receptor antagonists, fosfodiestarase-5 inhibitors or guanilate cyclase agonists.
• Under treatment with digoxin, flecainide, propafenone, dabigatran, tricyclic antidepressants, and other CYP2D6 inhibitors (other than betablockers).
• Severe COPD.
• Severe restrictive pulmonary disease.
• Participation in another clinical trial.
• Allergy to mirabegron or excipients.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The overall objective is to evaluate the efficacy and safety of mirabegron for the treatment of patients with PH secondary to HF. The primary objective is changes in PVR after 16 weeks of treatment.;Primary end point(s): Primary outcome will be the change from baseline to week 16 in PVR by RHC. PVR will be calculated in Wood units as:<br>(mean PAP [in mmHg] – PAWP [in mmHg])/cardiac output (L/min).;Timepoint(s) of evaluation of this end point: After 16 weeks of treatment;Secondary Objective: - 6-minute walking distance.<br>- NYHA functional class.<br>- Quality of life evaluated with the Kansas City Cardiomyopathy Questionnaire <br>- Dyspnea Borg scale score.<br>- Mean PAP assessed by RHC.<br>- Transpulmonary gradient.<br>- Diastolic pressure difference (diastolic PAP – PAWP).<br>- Cardiac output as assessed by RHC and CMR <br>- RV ejection fraction as assessed by CMR.<br>- NT-proBNP.

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: After 16 weeks of treatment;Secondary end point(s): - 6-minute walking distance.<br>- NYHA functional class.<br>- Quality of life evaluated with the Kansas City Cardiomyopathy Questionnaire <br>- Dyspnea Borg scale score.<br>- Mean PAP assessed by RHC.<br>- Transpulmonary gradient.<br>- Diastolic pressure difference (diastolic PAP – PAWP).<br>- Cardiac output as assessed by RHC and CMR <br>- RV ejection fraction as assessed by CMR.<br>- NT-proBNP.