Clinical Research Directory

Inclusion Criteria: * Signed informed consent prior to any trial-mandated procedure * Male or female ≥ 18 and ≤ 70 years of age * Symptomatic treatment-naïve PAH patients (group I) with confirmed diagnosis of one of the following subgroups: * idiopathic pulmonary arterial hypertension (IPAH) * hereditary pulmonary arterial hypertension (HPAH) * Drug and toxin-induced pulmonary arterial hypertension (DPAH) * PAH associated with Connective Tissue Disease * PAH with corrected congenital heart disease 4. Intermediate-high risk patients rated acc. the simplified four-strata risk-assessment tool or intermediate-low risk with severe hemodynamic impairment as defined in current PH guidelines i.e., mean right atrial pressure (RAP) ≥ 20 mmHg, cardiac index (CI) \< 2.0 L/min, stroke volume index (SVI) \< 31 mL/m2 and/or pulmonary vascular resistance (PVR) ≥ 12 WU * Right Heart Catheterization (RHC) meeting all the following criteria: * Mean pulmonary arterial pressure (mPAP) \> 20 mmHg * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg * PVR \> 2 Wood Units * Women of childbearing potential must not be pregnant or lactating, must perform regular pregnancy tests, if sexually active, agrees to continue to use reliable method(s) of contraception until study completion Exclusion Criteria: * PAH patients (group I) belonging to one of the following subgroups: * Schistosomiasis * HIV infection * Portal hypertension * Diffuse systemic sclerosis * Uncorrected congenital heart disease including uncorrected systemic-to-pulmonary shunts * Any PAH-specific drug therapy in the past 3 months * Patients responding to vasoreactivity testing with calcium channel blockers (CCB) * Post-capillary PH and left heart disease * Known or suspected pulmonary veno-occlusive disease (PVOD) * Any PH due to lung disease * Any disorder of the respiratory system expressed by Diffusing Capacity of Lung for Carbon Monoxide (DLCO) \<40% and a noticeable imaging result (e.g., CT) and (Total Lung Capacity) TLC \<60% and (Forced Expiratory Volume) FEV1 \<70% by plethysmography (a pulmonary function test) * Patients with need of ambulatory or long-term oxygen therapy * Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) \> 480 msec at screening * Body mass index (BMI) \> 35 (kg/m2) * Age \> 70 years * History of restrictive, constrictive or congestive cardiomyopathy, atrial septostomy, any symptomatic coronary disease events within 6 months, severe uncontrolled arterial hypertension, acutely decompensated heart failure and myocardial infarction within 30 days, significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease, chronic systemic hypotension, unstable angina pectoris, permanent/persistent atrial fibrillation and/or need for pacemaker * Patients with acute anemia with hemoglobin (Hb) values \<11g/dL * Cerebrovascular accident within 3 months * Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin \> 3× upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) \> ULN and/or Child-Pugh Class C * Documented renal insufficiency with Glomerular Filtration Rate (GFR) \<30 ml/min * Patients with untreated sleep apnea * Patient with other cardiovascular, liver, renal, hematologic, gastrointestinal (including active gastrointestinal ulcer), immunologic, endocrine (e.g., uncontrolled diabetes), metabolic, or central nervous system disease and acute bleeding and injuries (e.g., intracranial hemorrhage) that, in the opinion of the investigator, may adversely affect the safety of the patient and /or efficacy of the therapy or significantly limit the lifespan (\< 12 months) * Patients with major surgery in the last 12 months * Known history of alcohol abuse * Treatment of a a cytochrome P450 (CYP)2C8 enzyme inducer (e.g., rifampicin) ≤ 28 days and/or treatment of a CYP2C8 enzyme inhibitor (e.g., gemfibrozil) ≤ 28 days * Treatment with another investigational drug (planned, or taken ≤ 12 weeks) * Hypersensitivity to any of the trial treatments or any excipient of their formulations * Pregnancy, breastfeeding, or intention to become pregnant during the trial * Any other significant disease or disorder which, in the opinion of the investigator, may put the patients at risk when participating in the trial * Any factor or condition likely to affect protocol compliance of the patient, as judged by the investigator.