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

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, 12-week 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

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Macitentan
* Drug: Placebo


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

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: Macitentan<br>oral tablet, 10 mg once daily. | Drug: Macitentan<br>* oral tablet, 10 mg once daily<br>* Other names: ACT-064992;|
| Placebo Comparator: Placebo<br>Matching placebo, once daily. | Drug: Placebo<br>* matching placebo<br>* Other names: matching placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment | 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. | From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest |  | From randomization up to end of treatment period (Week 12) | 
| PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest | Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC). | From 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 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pre- and post-capillary pulmonary hypertension, CpcPH