Acute Pulmonary Hypertension MedDRA version: 20.0 Level: HLT Classification code 10037401 Term: Pulmonary hypertensions System Organ Class: 100000004855
Conditions
Interventions
Product Code: PDNO
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PDNO
CAS Number: 950478-73-6
Current Sponsor code: PDNO
Other descriptive name: 2-(nitrosooxy)propan-1-ol
Concentrati
Sponsors
Attgeno AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to understand and willing to sign an ICF after information at the pre-op screening visit. 2. Male and female patients, age = 18 years on the date of the informed consent at the time of the pre-op screening visit.* 3. Planned to undergo elective cardiopulmonary bypass (CPB) for CABG, AVR or MVR w or w/o CABG. Non-elective (emergency) surgery patients are not eligible. Concomitant CryoMaze procedure and/or surgical left atrial appendix occlusion as a treatment for atrial fibrillation is routinely performed in some of these patients and may be done. 4. Diagnosed with echocardiographic signs of pulmonary artery systolic pressure (PASP) =40 mmHg, as estimated by doppler defined echocardiography using a modified Bernoulli equation: PASP ˜ 4 (tricuspid regurgitant jet velocity)2 + CVP. *evaluated from medical history Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: Patients must not enter the study if any of the following exclusion criteria are fulfilled: 1. History of chronic PH (WHO group 1, 3, 4 or 5), not group 2 due to left heart disease, as judged by the Investigator.* 2. Patients with contraindications for PAC. 3. History of severe chronic obstructive pulmonary disease, as judged by the Investigator.* 4. Left heart failure with ejection fraction (EF) 450ms at the time of screening.* 7. High inotropic requirement (No more than one inotrope treatment and the vasopressor norepinephrine at time of screening/postoperative evaluation). 8. (Increased) mediastinal bleeding >100 mL/hour in mediastinal drainage at postoperative evaluation. 9. Mechanical circulatory assistance (IABP or R/L VAD). 10. Echocardiographic evidence of significant tricuspid insufficiency as judged by the Investigator at screening.* 11. Body Mass Index (BMI) >40 kg/m2.* 12. Estimated glomerular filtration rate (eGFR) 3%. 14. 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). 15. Preoperative haemoglobin 1.3, preoperative value. 18. Pregnant or lactating women, or with a positive pregnancy test at screening (for fertile women only). 19. 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. 20. 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.* 21. 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.* 22. History of any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at increased risk because of participation in the study, or influence the results or the ability to participate in the study.* 23. 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.* *evaluated from medical history
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: Part I: To evaluate the dose-range efficacy of PDNO on pulmonary vascular resistance (PVR) in patients undergoing CPB surgery with post-operative aPH. Part II: To evaluate the dose titration efficacy of PDNO on PVR in patients undergoing CPB surgery with post-operative aPH. ;Secondary Objective: Secondary objectives Part I: To evaluate the selectivity and dose-range of PDNO as a pulmonary vasodilator. To explore the effects of PDNO right ventricular function. To evaluate safety and tolerability of PDNO in patients undergoing CPB surgery. To assess the exposure of PD. Secondary objectives Part II: Evaluate the selectivity and dose titration of PDNO as a pulmonary vasodilator. Valuate safety and tolerability of PDNO in patients undergoing CPB surgery. To assess the exposure of PD. Exploratory objectives Part I: To explore potential biomarkers and to explore PD metabolites. To assess levels of fractional exhaled NO (FeNO) before and during iv infusion of PDNO. ;Primary end point(s): Primary endpoint Part I: Mean change in PVR from baseline (mean of T0 and T1) to time point T2, T3, T4, T5 and T6, respectively. PVR, will be derived as the mean pulmonary artery pressure (MPAP) - pulmonary capillary wedge pressure (PCWP) divided by cardiac output (CO), (PVR=(MPAP-PCWP)/CO), as measured with a pulmonary artery catheter (PAC) including thermodilution-determined cardiac output. Primary endpoint Part II: Mean change in PVR from baseline (mean of T0 and T1) to time point T2. PVR, will be derived as the mean pulmonary artery pressure (MPAP) - pulmonary capillary wedge pressure (PCWP) divided by cardiac output (CO), (PVR=(MPAP-PCWP)/CO), as measured with a pulmonary artery catheter (PAC) including thermodilution-determined cardiac output. ;Timepoint(s) of evaluation of this end point: Assessments will be done at the following timepoints for Part I: T0 (-15 min) and T1 (0 min) with placebo T2 (15 min), T3 (30 min), T4 (45 min), T5 (60 m | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For Part I: Mean change in PVR/SVR ratio from baseline (mean of T0 and T1) to time point T2, T3, T4, T5 and T6, respectively. Ratio PVR / systemic vascular resistance (SVR). SVR is determined from (MAP-CVP)/CO. Part II: Mean change in PVR/SVR ratio from baseline (mean of T0 and T1) to time point T2. Ratio PVR / systemic vascular resistance (SVR). SVR is determined from (MABP-CVP)/CO. ;Timepoint(s) of evaluation of this end point: Assessments will be done at the following timepoints for Part I: T0 (-15 min) and T1 (0 min) with placebo T2 (15 min), T3 (30 min), T4 (45 min), T5 (60 min), and T6 (75 min) with 3, 10, 30, 45, 60 nmol/kg/min with PDNO respectively T7 (85 min) and T8 (95 min) with placebo) Assessments will be done at the following timepoints for Part II: Assessments will be done at the following timepoints T0 (-15 min) and T1 (0 min) with placebo T2 (ca30 min) with PDNO T4 and T5 with placebo) | — |
Countries
Sweden
Contacts
Public ContactAnna Runeson
Scandinavian CRO
Outcome results
None listed