Normothermic Machine Perfusion (NMP) Versus Static Cold Storage (SCS) in Human Kidney Transplantation

NCT05031052 | Unknown DMC

• 1 other identifier: EA4/172/21
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Kidney Transplant; Complications; Kidney Failure; Graft Dysfunction

Keywords

ex-vivo machine perfusion; normothermic machine perfusion; kidney transplantation; extended criteria donation; donation after brain death; NMP

Outcome Measures

Primary Outcomes (1)

• Kidney function

  Estimated glomerular filtration rate (eGFR)

  After 6 months postoperatively

Secondary Outcomes (10)

• Kidney function

  After 3- and 12 months postoperatively

• Delayed graft function

  First 7 postoperative days

• Functional delayed graft function

  First 7 postoperative days

• Creatinine change ratio

  Day 2 and day 5 postoperatively

• Primary non function (PNF)

  After 3 months postoperatively

Study Arms (2)

Normothermic machine perfusion (NMP)

EXPERIMENTAL

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.

Device: End-ischemic normothermic oxygenated machine perfusion

Statical cold storage (SCS)

ACTIVE COMPARATOR

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.

Procedure: Static cold storage

Interventions

End-ischemic normothermic oxygenated machine perfusion DEVICE

Application of end-ischemic normothermic oxygenated machine perfusion at physiological temperatures for 4 hours.

Also known as: NMP

Normothermic machine perfusion (NMP)

Static cold storage PROCEDURE

Immediate implantation of kidney allograft after conventional and static preservation on ice

Also known as: SCS

Statical cold storage (SCS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Patients 18 years or older
• Patients suffering from end-stage kidney disease / kidney failure
• Listed for kidney transplantation
• Receiving ECD-allograft

You may not qualify if:

• Recipients of living donor kidney transplants
• Previous kidney transplantation
• Combined transplantations (liver-kidney, kidney-pancreas, etc.)
• Participation in other kidney related trials
• Unwilling or unable to follow the procedures outlined in the protocol
• Mentally or legally incapacitated

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (4)

Charité Universitaetsmedizin Berlin, Campus Mitte | Campus Virchow-Klinikum

Berlin, 13353, Germany

RECRUITING

Medizinische Hochschule Hannover (MHH), Department of Surgery and Transplantation

Hanover, 30625, Germany

NOT YET RECRUITING

University Hospital Heidelberg, Department of Surgery and Transplantation

Heidelberg, 69120, Germany

NOT YET RECRUITING

Ludwig-Maximilian's University, Campus Grosshadern, Department of General, Visceral, and Transplant Surgery

Munich, 81377, Germany

NOT YET RECRUITING

Related Publications (1)

• Tingle SJ, Thompson ER, Figueiredo RS, Moir JA, Goodfellow M, Talbot D, Wilson CH. Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD011671. doi: 10.1002/14651858.CD011671.pub3.

  PMID: 38979743 DERIVED

Related Links

• Study group webpage

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Georg Lurje, M.D.

CONTACT

+4930450652339; georg.lurje@charite.de

Deniz Uluk, M.D.

CONTACT

+4930450622187; deniz.uluk@charite.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant HPB- and Transplant Surgeon

Model Details: Multicenter prospective randomized controlled trial

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: September 1, 2021
• Study Start: May 10, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: June 13, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)