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Clinical Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction

Phase 2
Completed
Conditions
Pulmonary Hypertension
Interventions
Drug: Placebo
Registration Number
NCT02070991
Lead Sponsor
Actelion
Brief Summary

Study to evaluate if macitentan is safe and tolerable enough to be used for treatment of subjects with combined pre- and post-capillary pulmonary hypertension (CpcPH) due to left ventricular dysfunction.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
63
Inclusion Criteria
  1. Males and Females >=18 years of age
  2. Subjects with combined pre-and post-capillary Pulmonary Hypertension (CpcPH) due to left ventricular dysfunction (subset of WHO groups 2.1 and 2.2)
  3. Optimized diuretic therapy
Exclusion Criteria
  1. Types of Pulmonary Hypertension other than WHO groups 2.1 and 2.2 (Nice classification)
  2. Administration of PAH-specific therapy (i.e., Endothelin receptor antagonists (ERAs), Prostanoids, Phosphodiesterase 5 (PDE-5) inhibitors, guanylate cyclase stimulators)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MacitentanMacitentanoral tablet, 10 mg once daily.
PlaceboPlaceboMatching placebo, once daily.
Primary Outcome Measures
NameTimeMethod
Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatmentFrom randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day

The main endpoint is the number of participants who had at least one of the following: A) significant fluid retention, defined as increase in body weight at any time by ≥ 5% or ≥ 5 kg from baseline due to fluid overload and/or parenteral administration of diuretics. B) Worsening of NYHA functional class from baseline.

Secondary Outcome Measures
NameTimeMethod
PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at RestFrom randomization up to end of treatment period (Week 12)

Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC).

Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)From randomization up to end of treatment period (Week 12)
NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at RestFrom randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Cardiac Index (CI)From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG)From randomization up to end of treatment period (Week 12)

Trial Locations

Locations (32)

Medical University of Vienna and AKH Cardiology

🇦🇹

Vienna, Austria

The Lindner Clinical Trial Center

🇺🇸

Cincinnati, Ohio, United States

Krankenhaus der Elisabethinen Linz, 2. Interne Abteilung

🇦🇹

Linz, Austria

Ospedali Riuniti Di Trieste

🇮🇹

Trieste, Italy

Hôpital Erasme, Cliniques Universitaires de Bruxelles, Cardiologie

🇧🇪

Brussels, Belgium

Houston Methodist Hospital - Heart Failure/Pulm Hypertension

🇺🇸

Houston, Texas, United States

IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine)

🇨🇿

Praha, Czechia

Hospital Reina Sofia Servicio de Cardiologia

🇪🇸

Cordoba, Spain

Boston University School of Medicine

🇺🇸

Boston, Massachusetts, United States

Kentuckiana Pulmonary Associates

🇺🇸

Louisville, Kentucky, United States

University of Michigan Internal Medicine Cardiology, Pulmonary Hypertension Program

🇺🇸

Ann Arbor, Michigan, United States

Washington University School of Medicine - Center for Advanced Med

🇺🇸

Saint Louis, Missouri, United States

University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie

🇧🇪

Leuven, Belgium

Vancouver General Hospital - The Lung

🇨🇦

Vancouver, Canada

FN Brno-Bohunice, I. interní kardiologická klinika

🇨🇿

Brno, Czechia

DRK Klinken Berlin Kopenick Klinik für Innere Medizin Kardiologie

🇩🇪

Berlin, Germany

FN Olomouc, 1. Interní klinika - kardiologická

🇨🇿

Olomouc, Czechia

Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie

🇨🇿

Praha, Czechia

Hôpital Charles Nicolle Service de Cardiologie

🇫🇷

Rouen cedex, France

Universitätsklinik Schleswig-Holstein Campus Kiel Klinik für Innere Medizin III Kardiologie und Angiologie

🇩🇪

Kiel, Germany

Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin)

🇩🇪

Köln, Germany

Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Großhadern Schwerpunkt Pneumologie

🇩🇪

Munich, Germany

Carmel Medical Center, Pulmonary Unit

🇮🇱

Haifa, Israel

Kaplan Medical Centre / Pulmonary Institute and Department of Medicine

🇮🇱

Rehovot, Israel

Institute of Pulmonology Hadassah Medical Centre : Ein Karem

🇮🇱

Jerusalem, Israel

A.O. Universitaria Policlinico S. Orsola-Malpighi - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale - Unità Operativa di Cardiologia

🇮🇹

Bologna, Italy

The Chaim Sheba Medical Center / The Institute of Pulmonology, Physiology and Exercise

🇮🇱

Tel-Hashomer, Israel

Hospital Vall d´Hebron Servicio de Cardiologia

🇪🇸

Barcelona, Spain

Hospital Clinic Servicio de Cardiologia

🇪🇸

Barcelona, Spain

Hospital Universitario 12 Octubre Servicio de Cardiología

🇪🇸

Madrid, Spain

Centre Hospitalier Universitaire Vaudois Service de Cardiologie

🇨🇭

Lausanne, Switzerland

Universitätsklinik für Kardiologie Schweizer Herz- und Gefässzentrum Bern

🇨🇭

Bern, Switzerland

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