a study to evaluate the efficacy, safety and tolerability of pdno infusion in patients with pulmonary hypertension after cardiopulmonary bypass surgery

Conditions: Pulmonary Hypertension

Summary: 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

Keywords: acute pulmonary hypertension