Two-Drug combo may boost outcomes for High-Risk PAH patients

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Initial PAH diagnosis \< 6 months preceding randomisation * Negative vasoreactivity test * Treatment-naïve PAH (group 1): idiopathic, heritable, associated with drugs and toxin, associated with connective tissue disease, HIV infection or systemic-to-pulmonary congenital shunt corrected for more than one year * Meet all of the following hemodynamic criteria by means of a RHC prior to screening: * mPAP≥25 mmHg and * PAWP\<15 mmHg and * with PVR≥3 WU • Presence of at least two of the following criteria, as listed in the European pulmonary hypertension guidelines: * History of essential hypertension * Diabetes mellitus (any type) * Obesity (defined by a BMI ≥30 kg/m2) * Coronary heart disease (established by any of the following: history of myocardial infarction, history of percutaneous coronary intervention, angiographic evidence of coronary artery disease (\>50% stenosis in ≥1 vessel), positive ST, previous coronary artery bypass graft, stable angina) * Participant able to understand the study procedures * For women of childbearing potential (WOCBP), effective form of contraception\* from screening up to 1 month following discontinuation of the last study treatment * Affiliation to the french social security regime * Signed written informed consent Exclusion Criteria: * Porto-pulmonary hypertension * Uncorrected systemic-to-pulmonary congenital shunt * Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or CT pulmonary angiography * Patients listed for lung or heart-lung transplantation at time of screening * Patients on any PAH-specific drug therapy at any time preceding randomisation * Known moderate-to-severe restrictive lung disease (i.e., total lung capacity \< 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second \[FEV1\] \< 60% of predicted, with FEV1 / forced vital capacity \< 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema). * Known or suspected pulmonary veno-occlusive disease (PVOD) * Severe renal insufficiency (creatinine clearance \< 30 mL/min) * Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin \> 3 x ULN or serum AST and/or ALT \> 3xULN (assessed by local laboratory at screening) and/or Child-Pugh Class C. * Haemoglobin \< 10 g/dL * Patient under guardianship curatorship, deprived of liberty * Pregnant women, or breast-feeding women * Treatment with other PDE-5i for erectile dysfunction * Ongoing or planned treatment with nitrates and/or doxazosin. * Ongoing or planned treatment with riociguat * Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤28 days preceding randomisation