Renal Ex Vivo Warm Advanced Resuscitation Through Machine Perfusion (REWARM)

Renal Ex Vivo Warm Advanced Resuscitation Through Machine Perfusion - The REWARM Study

The REWARM study is an open label, randomized controlled clinical efficacy study, with primary outcome renal function 6 months after transplantation of kidneys recovered from deceased donors aged 50 years or older. Prior to transplantation, kidney grafts in the intervention group will receive 4-6 hours of NMP, following standard HMP and kidneys in the control group will only receive standard treatment, being HMP. It is a multi-center trial. Given the total annual 50+ deceased donor kidney transplantation volume of the three participating transplant centers combined, inclusions in the study are expected to last 2.5-3 years, aiming for a total of 140 patients in each of the two arms (280 patients total).

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant; Complications
• Intervention / Treatment: Procedure: Normothermic machine perfusion

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cyril Moers, MD, PhD; Phone Number: 0619602619; Email: c.moers@umcg.nl
• Study Contact Backup: Name: Kirsten Ma, PhD; Phone Number: 0625651635; Email: k.f.ma@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients receiving their first or second kidney transplant;
• Patients receiving a graft from a ≥ 50-year-old donor;
• Patients receiving a graft from a DCD or DBD donor;
• Patients receiving a kidney transplant in the UMCG, the Erasmus MC, or the LUMC;
• Patients receiving a graft stored on HMP;
• Patients ≥ 18 years of age;
• Patients having provided written informed consent.

Exclusion Criteria:

• Patients receiving their third or subsequent kidney transplant;
• Patients receiving a graft from a donor < 50 years;
• Patients receiving a graft not stored on HMP;
• Patients receiving a graft from a donor that underwent normothermic regional perfusion (NRP);
• Patients receiving a kidney transplant in another center than the UMCG, Erasmus MC, or LUMC;
• Patients receiving a multi-organ transplantation;
• Patients receiving a kidney with complex arterial anatomy (3 or more arteries);
• Recipients < 18 years of age.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Hypothermic machine perfusion
Active Comparator: Normothermic machine perfusion	Procedure: Normothermic machine perfusion; To determine whether a 4-6 hour period of normothermic machine perfusion, following standard hypothermic machine perfusion, results in better graft function after transplantation, compared to hypothermic machine perfusion preservation alone of kidneys recovered from deceased donors aged 50 years or older

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft function at twelve months after transplantation	The primary endpoint of this study is graft function at twelve months after transplantation, defined as the estimated glomerular filtration rate (eGFR).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient and graft survival	Patient and graft survival up to 12 months after transplantation	12 months
Occurence of delayed graft function (DGF) in the first 7 days after transplantation	DGF defined as dialysis requirement in the first week after transplantation, excluding dialysis for one-time hyperkaliemia in the first two days post-transplant	7 days
Duration of delayed graft function (DGF) in the first 7 days after transplantation	DGF defined as dialysis requirement in the first week after transplantation, excluding dialysis for one-time hyperkaliemia in the first two days post-transplant	7 days
Number of participants with primary non-function (PNF)	Incidence of primary non-function (PNF) defined as a permanent lack of graft function starting after transplantation.	12 months
Number of participants with biopsy-proven acute rejection		12 monts
estimated Glomerular Filtration Rate	eGFR at day 7, and 1, 3 and 6 months after transplantation	6 months
(serious) adverse events	Number of adverse (device) events and serious adverse (device) events	12 months
Postoperative complications		12 months
The mean serum concentration of creatinine in umol/L for each study arm	Biochemical analysis of graft function with patient serum and urine levels of creatinine at postoperative day 0-7, and 1, 3, 6 and 12 months after transplantation	12 months
The mean serum concentration of urea in umol/L for each study arm	Biochemical analysis of graft function with patient serum and urine levels of urea at postoperative day 0-7, and 1, 3, 6 and 12 months after transplantation	12 months
The mean serum concentration of sodium in umol/L for each study arm	Biochemical analysis of graft function with patient serum and urine levels of sodium at postoperative day 0-7, and 1, 3, 6 and 12 months after transplantation	12 months
The mean serum concentration of potassium in umol/L for each study arm	Biochemical analysis of graft function with patient serum and urine levels of potassium at postoperative day 0-7, and 1, 3, 6 and 12 months after transplantation	12 months
The mean serum concentration of proteins in umol/L for each study arm	Biochemical analysis of graft function with patient serum and urine levels of protein at postoperative day 0-7, and 1, 3, 6 and 12 months after transplantation	12 months

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2023
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): September 1, 2027

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 15911

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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