Prevention of delayed graft function in kidney transplant recipients Urological and Genital Diseases
Conditions
Interventions
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 carboxyhaemog
dose 3 will be administered 18-30 hours after dose 2. Participants will be followed for 84 days.
Sponsors
Proterris Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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 trial drug, as defined in the protocol. 6.3. In order to be considered “not of childbearing potential,” female subjects must be postmenopausal for at least 1 year at Screening and 1 year of amenorrhea, or have been irreversibly surgically sterilized by complete hysterectomy, oophorectomy, or bilateral tubal ligation for at least 6 months prior to the first administration of the trial drug. 7. Male subjects whose female partners are of childbearing potential (defined as above) must agree to use an acceptable method of birth control for the duration of trial treatment and for 28 days after the last administration of trial drug.
Exclusion criteria
Exclusion criteria: 1. Age less than 18 years or greater than 75. 2. Patients who lack mental capacity to give informed consent. 3. Multi-organ transplant recipients. 4. Subjects who are currently or, in the past 60 days, have been on experimental or unapproved medications, or who have been actively enrolled in a clinical trial investigating new therapies. Subjects enrolled in other observational (non-interventional) studies will not be excluded. 5. Subjects with significant pre-transplant anemia, whose serum Hb is 7.7 g/dL and therefore remain in the trial. 6. Subjects who are Jehovah’s witnesses or other subjects who will not accept blood transfusions. 7. Subjects who, in the opinion of the investigator, have unstable medical issues rendering them at significantly greater risk for adverse events in the peri-operative period, and specifically patients with a recent new-onset ( 40 kg/m2 14. Subjects who are being transplanted pre-emptively (not yet on dialysis) 15. Are pregnant, plan to become pregnant during this trial, are nursing mothers or are unwilling to use an acceptable method of contraception for the duration of the trial. 16. Have any serious or active medical or psychiatric illness, which in the opinion of the Investigator, would interfere with subjects’ treatment, assessment, or compliance with the protocol. 17. Have a history or suspicion of unreliability, poor cooperation, or non-compliance with medical treatment. 18. Have previously been randomized in this trial. 19. Have any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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] x 100 (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 | — |
Countries
England, United Kingdom
Contacts
Public ContactKourosh Saeb Cooke
Outcome results
None listed