Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure

NCT02775539 | Unknown Phase 2 DMC

• 1 other identifier: SPHERE-HF
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Pulmonary Hypertension; Mirabegron; Heart Failure; Pulmonary Vascular Resistance Abnormality

Keywords

Pulmonary hypertension; Mirabegron; Heart failure; B3 adrenergic

Outcome Measures

Primary Outcomes (1)

• Change in pulmonary vascular resistance (PVR) from baseline to week 16 assessed by right heart catheterization (RHC).

  16 weeks

Secondary Outcomes (14)

• Change from baseline in 6-minute walking distance

  16 weeks

• Change from baseline in NYHA functional class

  16 weeks

• Change from baseline in quality of life

  16 weeks

• Change from baseline in dyspnea Borg score

  16 weeks

• Change from baseline in mean PAP as assessed by RHC

  16 weeks

Study Arms (2)

Mirabegron

ACTIVE COMPARATOR

Oral mirabegron, starting with 50 mg once a day and titrated till a maximum of 200 mg once a day.

Drug: Mirabegron

Placebo

PLACEBO COMPARATOR

Oral placebo, similarly titrated to ensure blindness.

Drug: Placebo

Interventions

Mirabegron DRUG

Patients will receive 50 to 200 mg of mirabegron once a day during 16 weeks. Dose will be titrated during the first 8 weeks.

Mirabegron

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III: lead
• Hospital Clinic of Barcelona: collaborator
• Hospital Universitario 12 de Octubre: collaborator
• Puerta de Hierro University Hospital: collaborator
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: collaborator

Related Publications (1)

• Garcia-Lunar I, Blanco I, Fernandez-Friera L, Prat-Gonzalez S, Jorda P, Sanchez J, Pereda D, Pujadas S, Rivas M, Sole-Gonzalez E, Vazquez J, Blazquez Z, Garcia-Picart J, Caravaca P, Escalera N, Garcia-Pavia P, Delgado J, Segovia-Cubero J, Fuster V, Roig E, Barbera JA, Ibanez B, Garcia-Alvarez A. Design of the beta3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial. JACC Basic Transl Sci. 2020 Mar 11;5(4):317-327. doi: 10.1016/j.jacbts.2020.01.009. eCollection 2020 Apr.

  PMID: 32368692 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure

Interventions

mirabegron

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Central Study Contacts

Ana García-Álvarez, MD, PhD

CONTACT

003491 4531200; anagarci@clinic.ub.es

Borja Ibañez, MD, PhD

CONTACT

003491 4531200; bibanez@cnic.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2016
• First Posted: May 17, 2016
• Study Start: June 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: June 1, 2019
• Last Updated: May 17, 2016

Record last verified: 2016-05