An interventional study of Pump Eligible - Normothermia - Pump Both Kidneys and Pump Eligible - Hypothermia and Pump Right Kidney in Brain Death, Organ Donation and Organ Transplant Failure or Rejection, sponsored by University of California, San Francisco. Completed at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-14.
Sponsored by University of California, San Francisco · Not applicable, Interventional, and Prevention
To protect kidney function during the transplantation process by comparing mild hypothermia in the deceased organ donor before organs are recovered and pulsatile perfusion of the kidney after recovery and prior to transplantation.
BACKGROUND: In the initial Mild Hypothermia Randomized Control Trial (RCT), in collaboration with the Organ Procurement and Transplant (OPTN) Region 5 Donor Management Goals (DMG) Workgroup and Web Portal, the research team was able to conduct a multi-center RCT examining the benefits of mild hypothermia in donors after neurologic determination of death (DNDDs) on the outcomes of kidney transplantation. The trial was stopped early by the Data and Safety Monitoring Board (DSMB) due to a significant positive benefit to kidney transplant recipients, including a 38% reduction in the odds of delayed graft function (DGF, the primary outcome measure of the trial). The results of this study have been published in the New England Journal of Medicine (July 2015). This research offers a zero-cost intervention that can substantially increase transplant success as well as the pool of potential donors.
To expand upon the success of the hypothermia study, the team is conducting a new RCT to test whether hypothermia is as effective as machine perfusion (MP) of kidneys from DNDDs. In an RCT conducted by the Eurotransplant International Foundation in 2009 (Moers et al. NEJM), the protective effect of MP (OR = 0.57) was similar to that found in the Mild Hypothermia Trial (OR = 0.62). However, the cost of MP can be very significant for organ procurement organizations (OPOs) and transplant centers. MP of kidneys from deceased donors has been increasingly adopted by many centers even though clinical and cost effectiveness studies remain uncertain in the United States. Between 2012 and 2014, out of 31,798 kidneys available for transplant, 11,998 (38%) of them were machine perfused. Over the same three-year period, the number of kidneys pumped annually increased by over 20%. This is an opportune time to investigate the effectiveness of MP compared to mild hypothermia, as there are enough OPOs currently using MP that if mild hypothermia was found to be a non-inferior intervention, there would be considerable cost savings. Similarly, over 60% of kidneys do not receive machine perfusion and findings that demonstrates a benefit of machine perfusion would likely lead to rapid increase in use. In addition, DGF still occurs in up to 56% of high-risk kidneys despite using one of these protective measures and their combined use may be the best approach moving forward. Either way, a new evidence-based standard will be created that will significantly affect the way kidney transplants are handled.
METHODS: This will be a pragmatic multi-site randomized controlled trial that bases enrollment on each OPO/Donation Service Area's current pumping criteria. There will be two main groups of DNDDs,
(1) normothermia (36.5-37.5 C) plus MP of both kidneys (standard of practice control group), (2) mild hypothermia (34-35 C) plus MP of the left kidney only, and (3) mild hypothermia plus MP of the right kidney only.
In this manner, the same number of kidneys will be randomized to each of the three treatment strategies (MP alone, mild hypothermia alone, or MP + hypothermia). It is important to note that kidneys from "pump eligible"/higher risk DNDDs will still receive one form of protection and possibly two.
In contrast, "not pump eligible" DNDDs will only be randomized to one of two groups: (1) therapeutic mild hypothermia or (2) normothermia. Being that the Mild Hypothermia Trial was stopped early for efficacy in the overall DNDD population, there was insufficient statistical power to confirm a benefit in standard criteria donors (p=0.1 at stoppage). The purpose of this arm of the trial is to validate the protective effect of hypothermia in a larger sample size of lower-risk / "not pump eligible" donors.
The following objectives will be addressed by the trial:
Determine the non-inferiority of a hypothermia-only strategy to a standard pump-only strategy in high risk DNDDs
Evaluate the superiority of a combined hypothermia+MP strategy to both hypothermia or MP alone in high risk DNDDs
Evaluate the superiority of mild hypothermia versus standard of care normothermia in lower risk, "not pump eligible" DNDDs
Determine the safety of the hypothermia strategy with respect to the function of "bystander"organs (e.g., heart, lung)
This protocol has been approved by the OPTN Region 5 Research Committee. In addition, the following steps have been or will be taken:
A National communication was sent via TransplantPro to allow for a two-week period for public comment.
Only donors whose families and/or advanced directives (donor registry) have authorized research will be included in the study.
All organ offers from DNDDs enrolled in the study will include a message in the Donor Highlights section of DonorNet®, a copy of the study summary will be attached to the record, and allocation/transplantation will occur based on standard practice.
There will not be any interaction between the study team and the transplant recipients and no additional data will be collected.
Recipient graft function data will be derived from standard UNet forms and obtained from the OPTN in a de-identified format.
74 studies on the registry are indexed under Brain Death; 10 are open to participants now.
This study's enrollment of 1,427 is above the median of 154 across 39 interventional studies indexed under Brain Death.
Browse Brain Death studies →University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.
Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Normothermia and Machine Perfusion Deceased Donors will be kept normothermic (36.5-37.5 C) prior to organ recovery. Recovered kidneys will receive machine perfusion prior to implantation.
Other: Pump Eligible - Normothermia - Pump Both Kidneys
Deceased Donors will be kept mildly hypothermic (34-35 C) for at least 12 hours prior to organ recovery. Right Kidney will receive machine perfusion prior to implantation and the Left Kidney will receive cold storage.
Other: Pump Eligible - Hypothermia and Pump Right Kidney
Deceased Donors will be kept mildly hypothermic (34-35 C) for at least 12 hours prior to organ recovery. Left Kidney will receive machine perfusion prior to implantation and the Right Kidney will receive cold storage.
Other: Pump Eligible - Hypothermia and Pump Left Kidney
Deceased Donors will be kept normothermic (36.5-37.5 C) prior to organ recovery.
Other: Not Pump Eligible - Normothermia
Deceased Donors will be kept mildly hypothermic (34-35 C) for at least 12 hours prior to organ recovery.
Other: Not Pump Eligible - Hypothermia
Normothermia and Machine Perfusion Deceased Donors will be kept normothermic (36.5-37.5 C) prior to organ recovery. Recovered kidneys will receive machine perfusion prior to implantation.OPO's protocol
Deceased Donors will be kept mildly hypothermic (34-35 C) for at least 12 hours prior to organ recovery. Right Kidney will receive machine perfusion prior to implantation and the Left Kidney will receive cold storage. Recovered kidneys will be placed in University of Wisconsin for cold storage until reimplantation.
Deceased Donors will be kept mildly hypothermic (34-35 C) for at least 12 hours prior to organ recovery. Left Kidney will receive machine perfusion prior to implantation and the Right Kidney will receive cold storage.
Deceased Donors will be kept normothermic (36.5-37.5 C) prior to organ recovery. Pulsatile Perfusion of kidney grafts based on the respective OPO's protocol
Deceased Donors will be kept mildly hypothermic (34-35 C) for at least 12 hours prior to organ recovery.
Delayed Graft Function in Kidney Allografts
The incidence of DGF in kidneys from deceased donors enrolled in this trial, obtained from publically available OPTN data.
Time frame: 7 days
Allograft and Recipient survival for all transplanted organs
Allograft and Recipient survival for all transplanted organs from deceased donors enrolled in this trial obtained from publically available OPTN data.
Time frame: 1 year
Plan to share: No
Ran from Jul 2017 to primary completion in Jun 2022, 58 months.
Of 14 interventional studies with no phase under Brain Death, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 24 and three quarters within 52. This study's 58 months is above that.
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This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.
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