Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure

• Status: Unknown status
• Trial end date: 2019-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the efficacy and safety of mirabegron (a B3 adrenergic receptor agonist) in patients with pulmonary hypertension secondary to heart failure by conducting a randomized multicenter phase II placebo-controlled clinical trial.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Collaborators: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Hospital Clinic of Barcelona; Hospital Universitario 12 de Octubre; Puerta de Hierro University Hospital
• Treatments: Mirabegron

Criteria

Inclusion Criteria:

• Written inform consent;

• >18 years-old;

• HF with reduced or preserved ejection fraction, according to the definition of the European Society of Cardiology guidelines.

• Severe PH and/or combined postcapillary and precapillary PH (also knows as reactive or out-of-proportion PH) determined by RHC showing the following:

• Pulmonary arterial wedge pressure or end-diastolic left ventricular pressures ≥15 mmHg;

• Mean PAP≥25, and:

• PVR≥3 UW and/or diastolic gradient≥7 mmHg or

• Transpulmonary gradient≥12.

• NYHA functional class II-IV;

• 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.

Exclusion Criteria:

• Non-coronary cardiac surgery or non-coronary percutaneous procedure within the 12 months preceding recruitment or programmed;

• Myocardial infarction or coronary revascularization during the last 3 months,

• Myocardial resynchronization therapy initiated during the last 6 months;

• Sinus tachycardia or atrial fibrillation with uncontrolled heart rate (>100 bpm);

• Uncontrolled hypertension (PAS>180 or PAD>110 mmHg) or symptomatic hypotension (PAS<90 mmHg).

• Infiltrative myocardial disease.

• Expected survival <1 year due to a disease other than PH;

• Severe renal failure (GFR <30 mL/min/1.73 m2 or haemodialysis);

• Severe hepatic impairment (serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3x the upper limit of normality at screening;

• cQT interval on the ECG >430 ms in male or >450 ms in female;

• Concomitant use of specific pulmonary vasodilator therapy (i.e. endothelin receptor antagonists, phosphodiesterase -5 inhibitors, guanylate cyclase stimulators).

• Concomitant use of digoxin, flecainide, propafenone, dabigatran, tricycle antidepressants, or another strong inhibitors of CYP2D6 (with the exception of betablockers).

• Significant obstructive lung disease (FEV1/FVC<0.7 associated with FEV1<50% of predicted value).

• Significant restrictive lung disease (TLC<60%).

• Participation in another clinical trial.

• Female with childbearing potential.

• Known hypersensitivity to mirabegron or to any of its excipients.