PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial

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

Official Title
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A Randomized, Double-blind, Placebo-controlled, Prospective, Multicenter, Parallel Group Study to Assess the Safety and Efficacy of Macitentan in Patients With Portopulmonary Hypertension

Conditions
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Portopulmonary Hypertension

Intervention / Treatment
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* Drug: Macitentan
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Main 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational treatment<br>Macitentan film-coated tablet 10 mg once daily. | Drug: Macitentan<br>* Macitentan film-coated tablet 10 mg once daily.<br>* Other names: ACT-064992;|
| Placebo Comparator: Placebo<br>Matching placebo tablet once daily. | Other: Placebo<br>* Matching placebo tablet once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR). | The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR. | From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) | 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. | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in WHO Functional Class (FC) | 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. | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | 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. | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) | mRAP is the mean blood pressure in the right atrium of the heart. | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) | 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. | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in Cardiac Index | 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). | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) | 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. | From enrollment/baseline to Week 12 in the DB treatment period | 
| Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) | 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. | From enrollment/baseline to Week 12 in the DB treatment period |