STUDY OBJECTIVES Primary objective To evaluate the effect of macitentan 10 mg on pulmonary vascular resistance (PVR) as compared to placebo in subjects with pulmonary hypertension (PH) after left ventricular assist device (LVAD) implantation. Secondary objectives To evaluate the effect of macitentan 10 mg as compared to placebo on cardio-pulmonary hemodynamics and disease severity in subjects with PH after LVAD implantation. To evaluate the safety and tolerability of macitentan 10 mg in subjects with PH after LVAD implantation. Exploratory objectives To explore the potential effect of macitentan 10 mg as compared to placebo on right ventricular function in subjects with PH after LVAD implantation. To explore the potential effect of macitentan 10 mg as compared to placebo on selected clinical events in subjects with PH after LVAD implantation. To explore the potential effect of macitentan 10 mg as compared to placebo on renal function as measured by glomerular filtration rate (GFR) in subjects with PH after LVAD implantation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
57
2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
#125_Mayo Clinic Arizona
Phoenix, Arizona, United States
#144_University of Arizona
Tucson, Arizona, United States
#106_Cedars-Sinai Medical Center
Beverly Hills, California, United States
#154_University of California San Diego
La Jolla, California, United States
#110_Sutter Heart Institute
Sacramento, California, United States
Pulmonary Vascular Resistance (PVR) Ratio of Week 12 to Baseline
PVR ratio equals to Week 12 PVR / Baseline PVR. PVR represents the resistance against which the right ventricle needs to pump. PVR was calculated using the following formula: mean pulmonary arterial pressure (mPAP) - pulmonary artery wedge pressure (PAWP)/cardiac output (CO); where mPAP and PAWP were measured at end-expiration and CO was measured in triplicate using the thermodilution method.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
mRAP was collected in the eCRF (electronic case record form). Right atrial pressure (RAP) is the blood pressure in the right atrium of the heart. Change from baseline to Week 12 in mRAP was measured at rest and no correction for multiple testing was applied.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)
mPAP was collected in the eCRF. The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Change from baseline to Week 12 in mPAP was measured at rest and no correction for multiple testing was applied.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Pulmonary Arterial Wedge Pressure (PAWP)
PAWP was collected in the eCRF. PAWP is pressure within the pulmonary arterial system when the catheter tip is 'wedged' in the tapering branch of one of the pulmonary arteries. Change from baseline to Week 12 in PAWP was measured at rest and no correction for multiple testing was applied.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Cardiac Index (CI)
CI was calculated as Cardiac Output (CO)/body surface area (BSA), where CO is Thermodilution Cardiac Output (Liters per minute \[L/min\]) and BSA (m\^2) equals to 0.007184\*weight\^0.425 (kilograms)\*height\^0.725 (centimeter). CI was represented in liters per minute per square meter (L/min/m\^2). Change from baseline to Week 12 in CI was measured at rest and no correction for multiple testing was applied.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR)
TPR was calculated as mPAP/CO where mPAP is mean pulmonary arterial pressure and CO is cardiac output. Change from baseline to Week 12 in TPR was calculated at rest and no correction for multiple testing was applied.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SvO2)
Mixed venous oxygen saturation measures the end result of oxygen consumption and delivery. Change from baseline to Week 12 in SvO2 was reported and measured at rest and no correction for multiple testing was applied.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) Levels
NT-proBNP levels in the blood are used for diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in Participants World Health Organization (WHO) Functional Class (FC)
WHO FC is a classification which reflects disease severity based on symptoms. WHO Functional Classification of pulmonary hypertension comprises of Class I (participants with pulmonary hypertension but without resulting limitation of physical activity), II (participants with pulmonary hypertension resulting in slight limitation of physical activity), III (participants with pulmonary hypertension resulting in marked limitation of physical activity) and IV (participants with pulmonary hypertension with inability to carry out any physical activity without symptoms). Change from baseline in WHO FC was reported. WHO FC was categorized as worsening (change greater than \[\>\] 0); improvement (change less than \[\<\] 0); or no change (change equals to \[=\] 0).
Time frame: Baseline to Week 12
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#132_University of California San Francisco
San Francisco, California, United States
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Washington D.C., District of Columbia, United States
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Orlando, Florida, United States
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Chicago, Illinois, United States
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Oak Lawn, Illinois, United States
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