Heme Arginate in Transplantation Study (HOT2)
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|ClinicalTrials.gov Identifier: NCT03646344|
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : April 17, 2019
Organ shortage for transplant has necessitated use of kidneys from older donors, increasing the chance that the kidney will not work immediately or for as long as expected. The investigators gave the drug heme arginate (HA) to 20 kidney transplant patients in the first 24 hours after transplant, and showed that it may reduce kidney injury and is safe. The investigators plan to conduct a large study recruiting 600 patients to determine whether HA treatment increases the number of kidney transplants that work immediately. If successful, HA may be introduced into clinical practice at the end of this study.
Patients will be invited to take part in the study once listed for a kidney transplant. Further discussions will be had with them when admitted for transplant, and they will be offered the opportunity to participate. Consent will not be taken until the patient is admitted for transplantation. Following consent, participants will be randomised to receive either 2 doses of the study drug, HA, or a salt water solution, one at the time of transplant, and one approximately 24 hours later. Otherwise, treatment will be the same as any other patient undergoing a kidney transplant. Information about recovery from surgery, and specifically about kidney function, will be collected, but will not require additional blood tests. The study period ends after the first 7 days post-transplant, although longer term data will be collected from routine follow up appointments. Participants will be asked to complete a simple quality of life questionnaire 3 times: just before transplant, at approximately one week and three months after transplant.
|Condition or disease||Intervention/treatment||Phase|
|Renal Transplant Rejection Renal Transplant Failure||Drug: Heme Arginate 25 MG/ML Drug: 0.9% Sodium-chloride||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||600 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Multi-centre, parallel group 1:1 randomised placebo controlled trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||There will be an unblinded member of the research team (the individual administering the intervention) but otherwise the participant, the other members of the research team, the clinical team and blinded assessors will be blinded to the intervention.|
|Official Title:||Heme Arginate in Transplantation Study - a Multi-centre Blinded Parallel-group Randomised Trial of Heme Arginate Versus Placebo to Reduce Delayed Graft Function in Kidney Transplant Recipients|
|Actual Study Start Date :||March 12, 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2020|
Active Comparator: Active Group
Will receive Heme Arginate (IMP) at a dose of 3mg/kg over 30mins. Participants will receive infusions of the IMP at 2 time-points, the first prior to surgery (transplantation), and the second 20-28 hours later. At each infusion, the IMP will be followed by a 100ml infusion of 0.9% Sodium Chloride over 15mins.
Drug: Heme Arginate 25 MG/ML
IMP - to be administered at a dose of 3mg/kg to a maximum dose of 250mg over 30 mins. Participants will receive intervention twice during the trial, one on Day 0 (day of transplantation) and then again on D1 (20-28 hours after dose 1).
Placebo Comparator: Placebo Group
Will receive a 100ml infusion of 0.9% Sodium Chloride (placebo) over 30mins. Participants will receive infusions at 2 time-points, the first prior to surgery, and the second 20-28 hours later. At each infusion, the placebo will be followed by a further 100ml infusion of 0.9% Sodium Chloride over 15mins.
Drug: 0.9% Sodium-chloride
Placebo - 100ml of 0.9% Sodium Chloride will be given over 30 mins. Participants will receive intervention twice during the trial, one on Day 0 (day of transplantation) and then again on D1 (20-28 hours after dose 1).
- Delayed Graft Function [ Time Frame: 1 week post transplant ]The incidence of delayed graft function, defined as failure of a spontaneous fall in creatinine of >10% for each 3 consecutive day period in the first week following transplantation, with comparison between the two randomised groups.
- Requirement for dialysis [ Time Frame: 1 week post transplant ]The number of participants requiring dialysis within the first week post-transplant
- Time to functioning graft [ Time Frame: 1 week ]The number of days to functioning graft, defined as the spontaneous fall in creatinine of greater than, or equal to 10% over a period of 3 consecutive days in the first 7 days post transplant
- Length of hospital stay [ Time Frame: 3 months ]The number of days spent in hospital, along with level of care (ward/HDU/ITU), for the index admission (transplantation admission)
- Creatinine levels [ Time Frame: 3 months ]Serum creatinine levels at 1 and 3 months post-transplant across both randomised groups
- Acute rejection [ Time Frame: 3 months ]The number of participants with biopsy-proven acute rejection within the first 3 months post-transplant
- SF36 Quality of Life [ Time Frame: Up to 3 months post transplant ]A comparison of differences between groups in patient reported quality of life using the SF36
- Cost per QALY gained [ Time Frame: Up to 3 months post transplant ]Using data derived from the SF36 to weight survival for quality of life, Quality Adjusted Life Year (QALY) will be assessed
- 1 Year graft survival [ Time Frame: 1 year ]Graft survival rates at 1 year post transplant will be obtained from routinely collected data and differences between treatment groups assessed.
- 1 year recipient survival [ Time Frame: 1 year ]Recipient survival rates at 1 year post transplant will be obtained from routinely collected data and differences between treatment groups assessed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03646344
|Contact: Jean Antonelli||01316519920||Jean.Antonelli@ed.ac.uk|
|NHS Lothian - Royal Infirmary of Edinburgh||Recruiting|
|Edinburgh, Lothian, United Kingdom, EH16 4SA|
|Contact: Jean Antonelli 01316519920 Jean.Antonelli@ed.ac.uk|
|Principal Investigator: Andrew Sutherland|
|Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh||Active, not recruiting|
|Edinburgh, United Kingdom, EH16 4UX|
|Principal Investigator:||Lorna Marson||University of Edinburgh|