Hypothermic Oxygenated Machine Perfusion of Extended Criteria Kidney Allografts From Brain Death Donors

Hypothermic Oxygenated Machine Perfusion of Extended Criteria Kidney Allografts From Brain Death Donors - a Prospective Cohort Study

Kidney transplantation (KT) has emerged as the mainstay of treatment for end-stage kidney disease. In an effort to address the widening gap between demand and supply of donor organs, there has been an increase in the numbers of "marginal" or functionally impaired renal allografts that had to be accepted for KT over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function (PNF) and/or delayed graft function (DGF). Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in pre-clinical experiments and in a few clinical series of donation after cardiac death (DCD) in liver transplantation. The present trial is an investigator-initiated pilot study on the effects of HOPE on ECD-allografts in donation after brain death (DBD) KT. Fifteen kidney allografts will be submitted to 2 hours of HOPE before implantation and are going to be compared to a case matched group transplanted after conventional cold storage (CCS).

Study Overview

• Status: Completed
• Conditions: Reperfusion Injury; Hypothermic Oxygenated Machine Perfusion
• Intervention / Treatment: Other: Conventional cold storage; Procedure: HOPE

Detailed Description

The present trial is an investigator-initiated pilot study on the effects of HOPE on ECD-allografts in DBD KT. Fifteen kidney allografts with defined inclusion/exclusion criteria will be submitted to 2 hours of HOPE via the renal artery before implantation and are going to be compared to a case matched group of 30 patients (1:2 matching) transplanted after CCS. Besides the clinical evaluation of HOPE-"reconditioned" allograft function, a targeted biomarker analysis is planned using tissue, serum, and urine samples as the translational and basic research aspect of the present study.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Department of Surgery and Transplantation, University Hospital RWTH Aachen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Dialysis-requiring Patients, suffering from end stage kidney disease, listed for KT and receiving ECD organs at the Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany. Informed consent is obtained from all subjects participating in the trial by a qualified member of the study team.

ECD is defined as followed: deceased donors > 60 years and older, and those aged between 50-59 years with at least two of the following conditions: cerebrovascular cause of death, serum Creatinine greater than 1.5 mg/dL (132.6 µmol/L), history of arterial hypertension

Exclusion Criteria:

1. Recipients of living donor kidney transplants
2. Previous kidney transplantation
3. Participation in other kidney related trials
4. The subject received an investigational drug within 30 days prior to inclusion
5. The subject is unwilling or unable to follow the procedures outlined in the protocol
6. The subject is mentally or legally incapacitated
7. Non-German or non-English speakers
8. Family members of the investigators or employees of the participating department
9. The subject is mentally or legally incapacitated
10. The subject suffers from uncontrolled bacterial or viral infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional cold storage; Conventional static cold storage (CCS) on temperature 0-4 °C from organ procurement (historical case matched group)	Other: Conventional cold storage; No intervention
Experimental: Hypothermic oxygenated perfusion (HOPE); HOPE for 1 hour via the renal artery in a recirculating and pressure controlled system, Belzer (UW) machine perfusion solution, perfusate temperature 0-4 °C, perfusate oxygenation pO2 of 60-80 kPa Other Name: Hypothermic machine perfusion (HMP)	Procedure: HOPE; HOPE for 1 hour via the renal artery in a recirculating and pressure controlled system, Belzer (UW) machine perfusion solution, perfusate temperature 0-4 °C, perfusate oxygenation pO2 of 60-80 kPa Other Name: Hypothermic machine perfusion (HMP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DGF	DGF (defined as the need for dialysis in the first 7-days post-transplantation)	7 days post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR2, CRR5	Creatinine reduction ratio day 2 (CRR2= creatinine day 1-creatinine day 2/creatinine day 1) and CRR5 (CRR5=pre-transplant creatinine-creatinine day 5/pre-transplant creatinine)	5 days post-transplant
postoperative complications	Clavien-Dindo complication score	Subjects will be followed 6 months postoperatively
Cumulative postoperative complications	Comprehensive complication index (CCI)	Subjects will be followed 6 months postoperatively
Duration of intensive care stay	Duration of ICU stay	Subjects will be followed 6 months postoperatively
Duration of hospital stay	Duration of hospitalisation	Subjects will be followed 6 months postoperatively
Graft survival	Six months graft survival	Subjects will be followed 6 months postoperatively
Renal function	Renal function (serum creatinine and estimated glomerular filtration rate (eGFR))	Subjects will be followed 6 months postoperatively
Perfusion Parameter	Flow and thus renal resistance	During HOPE

Collaborators and Investigators

• Sponsor: University Hospital, Aachen
• Investigators: Principal Investigator: Georg Lurje, M.D., RWTH Aachen University

Publications and helpful links

General Publications

• Meister FA, Czigany Z, Rietzler K, Miller H, Reichelt S, Liu WJ, Boecker J, Moeller MJ, Tolba RH, Hamesch K, Strnad P, Boor P, Stoppe C, Neumann UP, Lurje G. Decrease of renal resistance during hypothermic oxygenated machine perfusion is associated with early allograft function in extended criteria donation kidney transplantation. Sci Rep. 2020 Oct 20;10(1):17726. doi: 10.1038/s41598-020-74839-7.
• Meister FA, Czigany Z, Bednarsch J, Bocker J, Amygdalos I, Morales Santana DA, Rietzler K, Moeller M, Tolba R, Boor P, Rohlfs W, Neumann UP, Lurje G. Hypothermic Oxygenated Machine Perfusion of Extended Criteria Kidney Allografts from Brain Dead Donors: Protocol for a Prospective Pilot Study. JMIR Res Protoc. 2019 Oct 14;8(10):e14622. doi: 10.2196/14622.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2017
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): March 30, 2020

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): April 7, 2020
• Last Update Submitted That Met QC Criteria: April 3, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Kidney transplantation; Extended criteria donor; Donation after brain death; HOPE
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Neurobehavioral Manifestations; Death; Unconsciousness; Consciousness Disorders; Body Temperature Changes; Coma; Reperfusion Injury; Hypothermia; Brain Death
• Other Study ID Numbers: EK 184-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No