Normothermic Machine Perfusion (NMP) Compared to Static Cold Storage (SCS) in Donation After Brain Death (DBD) Kidney Transplantation; a Prospective Multicenter Randomized Controlled Trial (NMP-DBD)

Status: Recruiting
Location: See all (4) locations...
Intervention Type: Device, Procedure
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

Due to organ shortage in kidney transplantation (KT) several strategies have been implemented in an attempt to increase donor pool utilization, including transplantation of extended criteria donor (ECD) allografts. While the transplantation of ECD organs saves patients from waiting-list dropout, these pre-damaged organs exhibit an increased susceptibility to further injury during organ storage and transplantation. Static cold storage (SCS) involves the transportation of procured donor kidneys on ice and has remained the gold standard for organ preservation for decades. SCS relies on hypothermia to reduce cellular metabolism and oxygen demand while achieving a prolonged preservation time of organs. Upon reperfusion, the reintroduction of oxygen to the ischemic kidney leads to a respiratory burst with massive production of mitochondrial reactive oxygen species and subsequent sterile inflammation of the entire organ. This ischemia-reperfusion injury (IRI) is a central predictor of graft and patient survival. Current clinical preservation strategies are unable to meet the challenges of ECD allograft transplantation and there is a great demand to optimize preservation techniques for such high risk ECD allografts. Currently, two main paradigms prevail in the clinical approach to kidney allograft machine perfusion (MP) in regard to optimized preservation techniques: while end-ischemic hypothermic (HMP) and hypothermic oxygenated MP (HOPE) may be seen as dynamic alternatives of the traditional organ preservation based on hypothermia-induced deceleration of metabolism could not proof a beneficial effect on delayed graft function or primary graft failure, the impact of normothermic perfusion (NMP) on ECD kidney allografts is still missing. NMP aims at re-equilibration of cellular metabolism by preserving the organ at physiological temperatures whilst ensuring sufficient oxygen and nutrient supply. The present trial was therefore designed to provide first level-II evidence for NMP in human KT after donation after brain death (DBD). In total, 194 human kidney grafts will be randomized to either 4 hours of NMP directly before implantation (intervention group; n = 97) or to SCS (control group; n = 97) prior to transplantation. The primary endpoint will be kidney function after 6 months (6-months eGFR). Secondary endpoints include kidney function after 3 and 12 months, incidence of delayed graft function (DGF), primary non-function (PNF) and surgical complications assessed by the comprehensive complication index (CCI).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Signed informed consent

• Patients 18 years or older

• Patients suffering from end-stage kidney disease / kidney failure

• Listed for kidney transplantation

• Receiving ECD-allograft

Locations
Other Locations
Germany
Charité Universitaetsmedizin Berlin, Campus Mitte | Campus Virchow-Klinikum
RECRUITING
Berlin
Medizinische Hochschule Hannover (MHH), Department of Surgery and Transplantation
NOT_YET_RECRUITING
Hanover
University Hospital Heidelberg, Department of Surgery and Transplantation
NOT_YET_RECRUITING
Heidelberg
Ludwig-Maximilian's University, Campus Grosshadern, Department of General, Visceral, and Transplant Surgery
NOT_YET_RECRUITING
Munich
Contact Information
Primary
Georg Lurje, M.D.
georg.lurje@charite.de
+4930450652339
Backup
Deniz Uluk, M.D.
deniz.uluk@charite.de
+4930450622187
Time Frame
Start Date: 2022-05-10
Estimated Completion Date: 2025-12-31
Participants
Target number of participants: 194
Treatments
Experimental: Normothermic machine perfusion (NMP)
End-ischemic NMP will be performed immediately after arrival of the allocated and static cold stored ECD kidney graft. The study protocol aims a duration of 4 hours. Machine perfusion will be performed with a combination of patient's blood group matched packed red blood cells (RBC) and a special manufactured solution with the currently only certified device in Europe (XVIVO - KidneyAssist®). After 4 hours of perfusion and viability assessment, the kidney allograft will be disconnected from the device immediately prior to transplantation and flushed with three litres of Custodiol HTK solution via the renal artery. Then transplantation will be performed in typical method.
Active_comparator: Statical cold storage (SCS)
Conventional method kidney transplantation of statical cold stored and transported ECD kidney allograft. The allocated kidney allograft will be flushed with Custodiol HTK solution during back table preparation with the aim of immediate implantation into recipient.
Related Therapeutic Areas
Sponsors
Leads: Charite University, Berlin, Germany

This content was sourced from clinicaltrials.gov