A Study to Evaluate the Efficacy, Safety and Tolerability of PDNO Infusion in Patients With Pulmonary Hypertension After Cardiopulmonary Bypass Surgery

Exclusion Criteria

• •History of chronic pulmonary hypertension (PH) (WHO group 1, 3, 4 or 5), not group 2 due to left heart disease
• •Patients with contraindications for pulmonary artery catheter (PAC)
• •History of severe chronic obstructive pulmonary disease
• •Left heart failure with ejection fraction (EF) \<35%
• •Non-ST elevation myocardial infarction (non-STEMI) or ST elevation myocardial infarction (STEMI) within 1 months prior to informed consent
• •Stroke (cerebrovascular lesion \[CVL\]), transient ischemic attack (TIA), AV block III within 3 months prior to informed consent or QTcF \>450ms at the time of screening
• •High inotropic requirement (no more than one inotrope treatment and the vasopressor norepinephrine at time of screening/postoperative evaluation)
• •(Increased) mediastinal bleeding \>100 mL/hour in mediastinal drainage at postoperative evaluation
• •Mechanical circulatory assistance (intra aortic balloon pump \[IABP\] or right/left-ventricular assist device \[R/L VAD\])
• •Echocardiographic evidence of significant tricuspid insufficiency
• •Body Mass Index (BMI) \>40 kg/m\^2
• •Estimated glomerular filtration rate (eGFR) \< 30 mL/min preoperative value
• •Methemoglobin \>3%
• •Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) (preoperative value)
• •Preoperative haemoglobin \<10 g/dL, postoperative: Hb \< 9 g/dL
• •Thrombocytopenia (platelet count \<100,000/mm\^3), preoperative value
• •Prothrombin time International ratio (INR) \> 1.3, preoperative value
• •Pregnant or lactating women, or with a positive pregnancy test at screening (for fertile women only)
• •Ongoing daily treatment the last 3 days with non-steroidal anti-inflammatory drugs (NSAIDs, excluding low dose, i.e. 75 mg, acetylsalicylic acid), new oral anticoagulants (NOACs), warfarin, heparin, clopidogrel (last 5 days). Low molecular weight heparin (LMWH) is not an exclusion criterion. Any use of PDE5 inhibitors (sildenafil, tadalafil, vardenafil and avanafil) within 48 hours prior to the administration of PDNO.
• •Known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated
• •History of allergy/hypersensitivity to PD or ongoing allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to PDNO
• •History of any other clinically significant disease or disorder
• •Participation in any interventional clinical study or has been treated with any investigational research products within 30 days or 5 half-lives, whichever is longer, prior to the initiation of screening