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

• Status: Recruiting
• Trial end date: 2023-04-23
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Attgeno AB
• Collaborator: Scandinavian CRO AB

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