Renal Ex Vivo Warm Advanced Resuscitation Through Machine Perfusion

Study Overview
=================
Brief Summary
-----------------
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).

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

Conditions
-----------------
Kidney Transplant; Complications

Intervention / Treatment
-----------------
* Procedure: Normothermic machine perfusion


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Hypothermic machine perfusion<br> | |
| Active Comparator: Normothermic machine perfusion<br> | Procedure: Normothermic machine perfusion<br>* 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<br>|

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 |