A study to evaluate the efficacy and safety of inhaled carbon monoxide on kidney function in patients who have received kidney transplants

INTERVENTION: Participants will be randomised (3:1 for Part A, and 1:1 for Part B) to receive 3 doses of inhaled CO (iCO) or placebo (medical air), with the aim of achieving (but not exceeding) a peak carboxyhaemoglobin (COHb) concentration of 10% (using an online tool to guide dosimetry). The iCO will be administered for a maximum of 90 minutes at 450 ppm (dose 1) or 300 ppm (doses 2 and 3). Dose 1 will be administered intra‐operatively at the time of kidney transplantation via the anesthesia circuit. Doses 2 and 3 will be administered post‐operatively via a respiratory mask. Dose 2 will be administered 18‐30 hours after dose 1, and; dose 3 will be administered 18‐30 hours after dose 2. Participants will be followed for 84 days. CONDITION: Prevention of delayed graft function in kidney transplant recipients ; Urological and Genital Diseases PRIMARY OUTCOME: Primary Outcome Measure (Safety):; Part A and Part B: The safety of iCO will be defined by the incidence of all reported adverse effects (AEs) including reported seriousness and relatedness as well as events leading to discontinuation of treatment or withdrawal from the trial at 84 days. The occurrence of AEs will be detected by monitoring vital signs, blood oxygenation, serum hematology and chemistry, urinalysis, and cardiac status by both telemetry and electrocardiograms (ECGs). AEs will be coded using MedDRA. The severity of AEs will be graded for severity (mild, moderate, severe or life‐threatening) based on the investigator’s assessment. The safety assessment will have an additional focus on pre‐specified administration‐associated events defined as recipient death, graft loss, and acute cardiovascular, respiratory and neurological adverse event reactions.; ; Primary Efficacy Objective (Part B only): ; The rate of delayed graft function (DGF) in kidney transplant recipients with DGF, defined by the need for at least one dialysis treatment within 7 days of transplant, at 84 days.; SECONDARY OUTCOME: Part B:; 1. Total number, timing and purpose of any dialysis required during the 84‐day period posttransplant; 2. Trajectory of change in serum creatinine, estimated glomerular filtration rate (eGFR) over the first 72 hours and 7 days post‐reperfusion of a donor kidney; 3. Creatinine Reduction Ratio: [(Creatinine Post‐Operative Day 1‐Creatinine Post‐Operative Day 2) / Creatinine Post‐Operative Day 1] X100 (Post‐operative Day 1 = Day after transplant date); 4. Daily urine volume post‐transplant prior to discharge from the hospital; 5. Urinary marker of kidney injury (NGAL and KIM‐1) up to discharge from hospital; INCLUSION CRITERIA: 1. Male and female adult subjects (age 18‐75) undergoing deceased kidney‐only transplants, including machine‐perfused kidneys. 2. Recipients of both donation after brainstem death (DBD) and donation after circulatory death (DCD) kidney transplants will be included. 3. Clinically stable in the opinion of the Investigator. 4. Willing and able to comply with the requirements of the study protocol (including required study visits). 5. Able to provide written informed consent (including consent for the use and disclosure of research‐related health information). 6. A female subject is eligible to enter the study if she is: 6.1. Not pregnant or nursing 6.2. Female subjects of childbearing potential must have a negative serum pregnancy within 48 hours prior to transplant surgery and must use a highly acceptable method of contraception for at least 3 months prior to the first administration of trial drug and for 28 days after the last administration of