Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH

Eligibility Criteria

• * WHO Category I PAH
• * Resting mPAP ≥ 25 mmHg with a wedge pressure of ≤ 15mmHg during right heart catheterization.
• * Need for parenteral TRE as determined by the PH specialist caring for the patient
• * Patients with a mean arterial pressure \<60, and/or requiring vasopressor support
• * Patients whom expected device (i.e. ECMO, RVAD) assistance or early pulmonary transplantation (within 3 months) seems inevitable
• * Patients with a left ventricular ejection fraction \<50% or clinical, echocardiographic, and/or catheterization data consistent with heart failure with preserved ejection fraction (HFpEF) and/or moderate-severe aortic or mitral valve abnormality
• * Patients with severe restrictive lung disease (FVC\<70% predicted) and/or obstructive lung disease (FEV1 \<70% predicted and FEV1/FVC \<70%).
• * Patients with a history of pulmonary embolism within the last three months or evidence of chronic pulmonary embolism.
• * Patients with a known contraindication to right heart catheterization.
• * Patients whom have received active or previous pulmonary vasoactive medication within the previous 12 weeks.
• * PAH associated with significant venous or capillary involvement (PCWP \> 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
• * Pulmonary Hypertension belonging to groups 2 to 5 of the WHO classification.
• * Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
• * Estimated creatinine clearance \< 30 mL/min
• * Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal.
• * Hemoglobin \< 75% of the lower limit of the normal range.
• * Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
• * Pregnant or breast-feeding.
• * Females must either abstain from intercourse (when it is in line with their preferred and usual lifestyle), or
• * Use 2 medically acceptable, highly effective forms of contraception for the duration of study, and at least 30 after discontinuing study drug.
• * Known concomitant life-threatening disease with a life expectancy \< 12 months.
• * Body weight \< 40 kg and/or \>150 kg.
• * Any condition that prevents compliance with the protocol or adherence to therapy.
• * Concurrent therapy with strong CYP3A4 inhibitors/inducers (i.e. protease inhibitors, azole antibiotics, macrolides), theophylline, and any medication in the PI's opinion may substantially potentiate the hypotensive effect of RIO.
• * Treatment with nitrates of any kind within the 4 weeks prior to enrollment.
• * Known hypersensitivity to drugs of the same class as TRE and/or RIO, or any of their excipients.
• * Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
• * Recent (\<6 months) hemoptysis and/or history of severe hemoptysis requiring intervention (bronchial artery embolization).