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

This is an open-label, multicenter study evaluating the dose, effect, safety and tolerability of intravenous PDNO infusion given to patients undergoing cardiopulmonary bypass (CPB) surgery with post-operative acute pulmonary hypertension (aPH).


Eligibility Criteria:
Inclusion Criteria:

* Ability to understand and willing to sign an informed consent form (ICF)
* Male and female patients, age ≥ 18 years
* Planned to undergo elective cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG), aortic valve repair (AVR) or mitral valve repair (MVR) with or without CABG
* Diagnosed with echocardiographic signs of pulmonary artery systolic pressure (PASP) \>50 mmHg , as estimated by doppler defined echocardiography using a modified Bernoulli equation: PASP ≈ 4 (tricuspid regurgitant jet velocity)\^2 + central venous pressure (CVP)

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