search
Back to results

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

Primary Purpose

Kidney Transplant; Complications, Kidney Failure, Graft Dysfunction

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
End-ischemic normothermic oxygenated machine perfusion
Static cold storage
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Transplant; Complications focused on measuring ex-vivo machine perfusion, normothermic machine perfusion, kidney transplantation, extended criteria donation, donation after brain death, NMP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  • Recipients of living donor kidney transplants
  • Previous kidney transplantation
  • Combined transplantations (liver-kidney, kidney-pancreas, etc.)
  • Participation in other kidney related trials
  • Exposure to an investigational drug within 30 days prior to inclusion
  • Unwilling or unable to follow the procedures outlined in the protocol
  • Mentally or legally incapacitated

Sites / Locations

  • Charité Universitaetsmedizin Berlin, Campus Mitte | Campus Virchow-KlinikumRecruiting
  • Medizinische Hochschule Hannover (MHH), Department of Surgery and Transplantation
  • University Hospital Heidelberg, Department of Surgery and Transplantation
  • Ludwig-Maximilian's University, Campus Grosshadern, Department of General, Visceral, and Transplant Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Normothermic machine perfusion (NMP)

Statical cold storage (SCS)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Kidney function
Estimated glomerular filtration rate (eGFR)

Secondary Outcome Measures

Kidney function
Estimated glomerular filtration rates (eGFR)
Delayed graft function
Incidence (absolute and percentage numbers) and duration (in days) of delayed graft function (defined as the period between kidney transplant and last dialysis)
Functional delayed graft function
Incidence (absolute and relative numbers) and duration (in days) of functional DGF (defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplantation)
Creatinine change ratio
Creatinine change ratio at day 2 (referred to day 1) and Creatinine change ratio at day 5 (referred to pretransplant serum Creatinine)
Primary non function (PNF)
Incidence of PNF descriped as persisting dialysis dependency after kidney transplantation
Incidence and severity of postoperative complications
Assessed by the Clavien-Dindo complication score and the comprehensive complication index (CCI®)
Hospitalization
Duration of hospital stay
Cost analysis
Total costs of treatment and hospital stay
Recipient- and graft survival
One-year recipient- and graft survival
Acute rejection incidence
Biopsy proven acute rejection

Full Information

First Posted
August 23, 2021
Last Updated
June 10, 2022
Sponsor
Charite University, Berlin, Germany
search

1. Study Identification

Unique Protocol Identification Number
NCT05031052
Brief Title
Normothermic Machine Perfusion (NMP) Versus Static Cold Storage (SCS) in Human Kidney Transplantation
Acronym
NMP-DBD
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 10, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
The first human kidney transplantation (KT) was performed by Murray et al. in 1954 and has evolved as the standard treatment for kidney failure (previously referred to as end-stage renal disease (ESRD). In 2020, approximately 7067 patients were listed for KT in Germany, however only 1342 transplantations could be performed due to organ shortage. The number of patients on the waiting list substantially exceeds the number of donors. Around 390 patients died while waiting for a suitable organ on the waiting list, and another 492 patients dropped out due to morbidity and advancing disease. For increasing donor pool utilization several strategies have been aimed, including living donation, old-for-old KT and transplantation of extended criteria donor (ECD) allografts. While, ECD allografts are associated with a higher incidence of graft related complications and impaired postoperative outcome, novel preservation techniques such as ex-vivo machine perfusion (MP) of the donor allograft have been developed aiming at optimizing the function of marginal organs after transplantation. The common practice of static cold storage (SCS) organ preservation has changed little since the initial introduction of the original University of Wisconsin (UW) organ preservation solution in the late 1980s. Static organ preservation relies on hypothermia to decelerate metabolism and reduce oxygen demand to prolong ischemia tolerance and avoid rapid functional graft impairment, thereby delaying graft damage. While a significant amount of anaerobic metabolism continues at a low rate, the metabolism of the allograft does not cease completely during SCS. In addition, the lack of blood flow-derived shear stress causes a disruption of endogenous nitric-oxide (NO) production and a functional impairment of endothelial cells. Upon reperfusion, the reintroduction of oxygen-rich blood to the ischemic allograft leads to a respiratory-burst with massive reactive oxygen species (ROS) production, mitochondrial oxidative stress and a sterile inflammatory reaction that is pivotal to kidney injury. This cascade of ischemia-reperfusion injury (IRI) ultimately leads to an impaired outcome, especially in the ECD-KT setting. While high-quality grafts are usually less prone to IRI, ECD allografts exhibit an impaired microcirculation and an increased susceptibility to inflammatory and oxidative stress and, as such, poorly tolerate extended periods of cold storage. In recent years, MP has been recognized as a promising strategy in the context of ECD kidney transplantation. While SCS only prolongs storage time and limits the damage sustained during the period of cold ischemia, MP can reverse some of these effects. Hypothermic (HMP) and hypothermic oxygenated MP (HOPE) may be seen as dynamic cold organ preservation based on hypothermia-induced deceleration of metabolism, which aims to combine the positive effects of hypothermia observed in classical cold storage with the positive effects of dynamic preservation. In contrast normothermic perfusion (NMP) mimics physiological circumstances and provides sufficient oxygen and nutrient supply. End-ischemic HMP with oxygen (HOPE) presents is marked by active oxygenation of the perfusate during MP. Even though beneficials effects of HOPE were reported in preclinical studies, no significant impact on DGF, PNF or graft survival after one year in human KT could be demonstrated. In contrast to hypothermic preservation methods, data on NMP in human KT is limited. In fact, there are no registered randomized controlled clinical trials (RCT), comparing end-ischemic NMP versus SCS in donation after brain death (DBD), the only legal donation circumstance in Germany. The aim of this study is to investigate the impact of end-ischemic NMP compared to SCS in a multicenter prospective randomized controlled clinical trial (RCT) using ECD kidney allografts from DBD donors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Multicenter prospective randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
194 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Normothermic machine perfusion (NMP)
Arm Type
Experimental
Arm Description
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.
Arm Title
Statical cold storage (SCS)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
End-ischemic normothermic oxygenated machine perfusion
Other Intervention Name(s)
NMP
Intervention Description
Application of end-ischemic normothermic oxygenated machine perfusion at physiological temperatures for 4 hours.
Intervention Type
Procedure
Intervention Name(s)
Static cold storage
Other Intervention Name(s)
SCS
Intervention Description
Immediate implantation of kidney allograft after conventional and static preservation on ice
Primary Outcome Measure Information:
Title
Kidney function
Description
Estimated glomerular filtration rate (eGFR)
Time Frame
After 6 months postoperatively
Secondary Outcome Measure Information:
Title
Kidney function
Description
Estimated glomerular filtration rates (eGFR)
Time Frame
After 3- and 12 months postoperatively
Title
Delayed graft function
Description
Incidence (absolute and percentage numbers) and duration (in days) of delayed graft function (defined as the period between kidney transplant and last dialysis)
Time Frame
First 7 postoperative days
Title
Functional delayed graft function
Description
Incidence (absolute and relative numbers) and duration (in days) of functional DGF (defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplantation)
Time Frame
First 7 postoperative days
Title
Creatinine change ratio
Description
Creatinine change ratio at day 2 (referred to day 1) and Creatinine change ratio at day 5 (referred to pretransplant serum Creatinine)
Time Frame
Day 2 and day 5 postoperatively
Title
Primary non function (PNF)
Description
Incidence of PNF descriped as persisting dialysis dependency after kidney transplantation
Time Frame
After 3 months postoperatively
Title
Incidence and severity of postoperative complications
Description
Assessed by the Clavien-Dindo complication score and the comprehensive complication index (CCI®)
Time Frame
90-days and 1-year postoperatively
Title
Hospitalization
Description
Duration of hospital stay
Time Frame
Follow-up duration of 1-year
Title
Cost analysis
Description
Total costs of treatment and hospital stay
Time Frame
Follow-up duration of 1-year
Title
Recipient- and graft survival
Description
One-year recipient- and graft survival
Time Frame
Follow-up duration of 1-year
Title
Acute rejection incidence
Description
Biopsy proven acute rejection
Time Frame
Follow-up duration of 1-year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent Patients 18 years or older Patients suffering from end-stage kidney disease / kidney failure Listed for kidney transplantation Receiving ECD-allograft Exclusion Criteria: Recipients of living donor kidney transplants Previous kidney transplantation Combined transplantations (liver-kidney, kidney-pancreas, etc.) Participation in other kidney related trials Exposure to an investigational drug within 30 days prior to inclusion Unwilling or unable to follow the procedures outlined in the protocol Mentally or legally incapacitated
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Georg Lurje, M.D.
Phone
+4930450652339
Email
georg.lurje@charite.de
First Name & Middle Initial & Last Name or Official Title & Degree
Deniz Uluk, M.D.
Phone
+4930450622187
Email
deniz.uluk@charite.de
Facility Information:
Facility Name
Charité Universitaetsmedizin Berlin, Campus Mitte | Campus Virchow-Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georg Lurje, M.D.
Phone
+4930450652339
Email
georg.lurje@charite.de
First Name & Middle Initial & Last Name & Degree
M.D.
First Name & Middle Initial & Last Name & Degree
Georg Lurje, M.D.
Facility Name
Medizinische Hochschule Hannover (MHH), Department of Surgery and Transplantation
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florian Vondran, M.D.
Email
vondran.florian@mh-hannover.de
Facility Name
University Hospital Heidelberg, Department of Surgery and Transplantation
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arianeb Mehrabi, M.D.
Email
arianeb.mehrabi@med.uni-heidelberg.de
Facility Name
Ludwig-Maximilian's University, Campus Grosshadern, Department of General, Visceral, and Transplant Surgery
City
Munich
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Markus Guba, M.D.
Email
markus.guba@med.uni-muenchen.de
First Name & Middle Initial & Last Name & Degree
Dionysios Koliogiannis, M.D.
Email
dionysios.koliogiannis@med.uni-muenchen.de

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.hopeliver.com
Description
Study group webpage

Learn more about this trial

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

We'll reach out to this number within 24 hrs