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PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial

Phase 4
Completed
Conditions
Portopulmonary Hypertension
Interventions
Other: Placebo
Registration Number
NCT02382016
Lead Sponsor
Actelion
Brief Summary

24-week study to evaluate the efficacy and safety of macitentan for the treatment of portopulmonary hypertension.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
85
Inclusion Criteria
  • Male or female of at least 18 years of age
  • Confirmed diagnosis of portopulmonary hypertension

Main

Exclusion Criteria
  • Severe hepatic impairment
  • Severe obstructive or restrictive lung disease
  • Pulmonary veno-occlusive disease
  • Systolic blood pressure (SBP) < 90 mmHg at Screening
  • ALT/AST >= 3 x ULN
  • Bilirubin >= 3 mg/dL at Screening
  • Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboMatching placebo tablet once daily.
Investigational treatmentMacitentanMacitentan film-coated tablet 10 mg once daily.
Primary Outcome Measures
NameTimeMethod
Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR).From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period

The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)From enrollment/baseline to Week 12 in the DB treatment period

NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary hypertension (PH). The relative change from baseline to Week 12 in NT-proBNP is expressed as a ratio of Week 12 to baseline NT-proBNP.

Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)From enrollment/baseline to Week 12 in the DB treatment period

mRAP is the mean blood pressure in the right atrium of the heart.

Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2)From enrollment/baseline to Week 12 in the DB treatment period

SVO2 help assess tissue oxygen delivery. It describes the percentage of oxygen bound to hemoglobin in the blood which returns to the heart. This reflects the amount of residual oxygen in the blood after oxygen extraction by the tissues throughout the body.

Change From Baseline to Week 12 in Cardiac IndexFrom enrollment/baseline to Week 12 in the DB treatment period

The cardiac index is an assessment of the function of the heart and relates the cardiac output to the patient's body size (the patient's body surface area).

Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR)From enrollment/baseline to Week 12 in the DB treatment period

TPR is the resistance the pulmonary circulation that must be overcome in order for the blood flow to occur. It takes into account the blood pressure in the pulmonary arteries and the cardiac output. It is an important measurement to monitor the function of the pulmonary circulation and detect disease progression or improvement.

Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD)From enrollment/baseline to Week 12 in the DB treatment period

The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.

Change From Baseline to Week 12 in WHO Functional Class (FC)From enrollment/baseline to Week 12 in the DB treatment period

Changes from baseline to Week 12 in WHO FC were dichotomized as worsening (i.e., change \> 0) versus no change or improvement (i.e., change ≤ 0). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.

Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP)From enrollment/baseline to Week 12 in the DB treatment period

mPAP is the mean blood pressure inside the pulmonary artery which moves the blood from the heart to the lungs. Monitoring of mPAP can detect small changes in the function of the heart.

Trial Locations

Locations (51)

David Geffen School of Medicine, UCLA

🇺🇸

Los Angeles, California, United States

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

🇨🇿

Prague, Czechia

Hospital Universitario12 Octubre

🇪🇸

Madrid, Spain

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

🇨🇿

Prague, Czechia

The Royal Free Hospital/ Cardiology Department

🇬🇧

London, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

🇬🇧

Sheffield, United Kingdom

Thoraxklinik des Universitätsklinikums Heidelberg Zentrum für pulmonale Hypertonie Studienkoordination

🇩🇪

Heidelberg, Germany

Hospital Clinico i Provincial Servicio de Neumología

🇪🇸

Barcelona, Spain

Boston University

🇺🇸

Boston, Massachusetts, United States

Kentuckiana Pulmonary Associates

🇺🇸

Louisville, Kentucky, United States

University of Miami

🇺🇸

Miami, Florida, United States

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

🇩🇪

Dresden, Germany

Keck School of Medicine

🇺🇸

Los Angeles, California, United States

UCSD

🇺🇸

La Jolla, California, United States

Emory Healthcare

🇺🇸

Atlanta, Georgia, United States

Piedmont Healthcare

🇺🇸

Austell, Georgia, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

University of New Mexico Health Science Center

🇺🇸

Albuquerque, New Mexico, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Baylor University Medical Center

🇺🇸

Dallas, Texas, United States

Cleveland Clinic - Department of Cardiovascular Medicine

🇺🇸

Cleveland, Ohio, United States

UPMC Montefiore

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center Division of NeuroCritical Care 75390-8550

🇺🇸

Dallas, Texas, United States

University of Colorado Health Sciences Center Aurora

🇺🇸

Aurora, Colorado, United States

Mayo Clinic -Clinical Studies Unit

🇺🇸

Phoenix, Arizona, United States

UCSF

🇺🇸

San Francisco, California, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Methodist Hospital

🇺🇸

San Antonio, Texas, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Medizinische Hochschule Hannover, Abteilung Pneumologie

🇩🇪

Hannover, Germany

CHU Toulouse - Hôpital Larrey Hôpital de Jour et Semaine

🇫🇷

Toulouse, France

CHRU Hôpital Cavale Blanche Brest

🇫🇷

Brest, Bretagne, France

Universitätsklinikum Giessen und Marburg GmbH Justus-Liebig Universität Giessen 35392

🇩🇪

Giessen, Germany

Mayo Clinic Florida - Pulmonary Dept.

🇺🇸

Jacksonville, Florida, United States

Hôpital Kremlin Bicêtre Service de Pneumologie

🇫🇷

Paris, France

CHU Côte de Nacre, Service de Pneumologie

🇫🇷

Caen, France

Hôpital cardiologique, Service de cardiologie 59037 Lille Cedex"

🇫🇷

Lille, France

Hôpital Pontchaillou - CHU Rennes Service de Cardiologie et des Maladies Vasculaires Rennes Cedex 9 35033"

🇫🇷

Rennes, France

University of Florida - Divison of Pulmonary Critical Care & Sleep

🇺🇸

Gainesville, Florida, United States

Servico de Hipertensao Pulmonar - Complexo Hospitalar Santa Casa Irmandade Santa de Misericordia de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Universitätsklinikum Leipzig, Department Innere Medizin, Abteilung Pneumologie

🇩🇪

Leipzig, Germany

University of Florida College of Medicine

🇺🇸

Jacksonville, Florida, United States

South Miami Hospital

🇺🇸

South Miami, Florida, United States

Hôpital Cardiologique et Pneumologique Louis Pradel 69677 Bron cedex"

🇫🇷

Lyon, France

NHS Greater Glasgow and Clyde Trust

🇬🇧

Glasgow, Scotland, United Kingdom

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP)

🇧🇷

Sao Paulo, Brazil

CHRU de Grenoble, Hôpital Albert Michallon

🇫🇷

Grenoble, Rhône- Alpes, France

CHU Rouen

🇫🇷

Rouen, France

University of Wisconsin-Madison

🇺🇸

Madison, Wisconsin, United States

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