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

Prior treatment

• Patients whom expected device (i.e. ECMO, RVAD) assistance or early pulmonary transplantation (within 3 months) seems inevitable
• Patients whom have received active or previous pulmonary vasoactive medication within the previous 12 weeks.
• 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.
• 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.
• Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.

Other illness

• 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.
• 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.
• Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
• Any condition that prevents compliance with the protocol or adherence to therapy.
• Known hypersensitivity to drugs of the same class as TRE and/or RIO, or any of their excipients.
• Recent (\<6 months) hemoptysis and/or history of severe hemoptysis requiring intervention (bronchial artery embolization).

Lab values

• 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
• 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.

Other

• Patients with a mean arterial pressure \<60, and/or requiring vasopressor support
• Body weight \< 40 kg and/or \>150 kg.

• 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