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

Not Applicable

Completed

• Conditions: Reperfusion Injury; Hypothermic Oxygenated Machine Perfusion
• Interventions: Procedure: HOPE; Other: Conventional cold storage

• Registration Number: NCT03378817
• Lead Sponsor: University Hospital, Aachen

Brief Summary

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).

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 Timeline

• Study Start: 2017-12-05
• Study First Submitted: 2017-12-08
• Study First Submitted QC: 2017-12-14
• Study First Posted: 2017-12-20
• Primary Completion: 2019-09-30
• Study Completion: 2020-03-30
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-03
• Last Update Posted: 2020-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hypothermic oxygenated perfusion (HOPE)	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)
Conventional cold storage	Conventional cold storage	Conventional static cold storage (CCS) on temperature 0-4 °C from organ procurement (historical case matched group)

Primary Outcome Measures

Name	Time	Method
DGF	7 days post-transplant	DGF (defined as the need for dialysis in the first 7-days post-transplantation)

Secondary Outcome Measures

Name	Time	Method
Perfusion Parameter	During HOPE	Flow and thus renal resistance
Renal function	Subjects will be followed 6 months postoperatively	Renal function (serum creatinine and estimated glomerular filtration rate (eGFR))
postoperative complications	Subjects will be followed 6 months postoperatively	Clavien-Dindo complication score
CRR2, CRR5	5 days post-transplant	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)
Cumulative postoperative complications	Subjects will be followed 6 months postoperatively	Comprehensive complication index (CCI)
Duration of intensive care stay	Subjects will be followed 6 months postoperatively	Duration of ICU stay
Duration of hospital stay	Subjects will be followed 6 months postoperatively	Duration of hospitalisation
Graft survival	Subjects will be followed 6 months postoperatively	Six months graft survival

Trial Locations

Locations (1)

Department of Surgery and Transplantation, University Hospital RWTH Aachen; 🇩🇪 Aachen, Germany