Intermittent Versus Continuous Surface O2 During HMP of DCD Kidneys

Study Overview
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Brief Summary
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The aim of the study is to evaluate the feasibility of this bubble and surface oxygenation and to determine the optimal timing of surface oxygenation (continuous versus intermittent) as alternative for membrane-oxygenated kidneys, originating from DCD donors, during HMP on early graft function in clinical practice.

Detailed Description
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Kidneys originating from deceased donors after circulatory death (DCD), category 3 and 5 (controlled) will be preserved from procurement until transplantation on hypothermic machine perfusion conditions and prospectively randomized into 2 study groups: 1) intermittent surface oxygenation during HMP (surface oxygenation interrupted during organ transport (2-4h)(I-HMPO2 group), and 2) continuous surface oxygenation during HMP (surface oxygenation during the whole machine preservation period included organ transport)(C-HMPO2 group).

Official Title
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A Prospective Feasibility Trail to Compare the Efficacy of Intermittent Surface Oxygenation With Continuous Surface Oxygenation During Hypothermic Machine Perfusion of Kidneys Donated After Circulatory Death

Conditions
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Delayed Graft Function, Kidney Transplant; Complications, Ischemia Reperfusion Injury, Mitochondrial

Intervention / Treatment
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* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Listed for a renal transplantation due to end stage renal disease Willingness to comply with the protocol procedures for the duration of the study included scheduled follow-up visits and examinations. Exclusion Criteria: Multi-organ recipients Dual kidney transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Kidneys originating from deceased donors after circulatory death (DCD), category 3 and 5 (controlled) will be preserved from procurement until transplantation on hypothermic machine perfusion conditions and prospectively randomized into 2 study groups: 1) intermittent surface oxygenation during HMP (surface oxygenation interrupted during organ transport (2-4h)(I-HMPO2 group), and 2) continuous surface oxygenation during HMP (surface oxygenation during the whole machine preservation period included organ transport)(C-HMPO2 group)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I-HMPO2<br>intermittent surface oxygenation during hypothermic machine perfusion (surface oxygenation interrupted during organ transport) | Drug: Oxygen<br>* Active oxygenation during hypothermic machine perfusion by bubble and surface oxygenation. Intermittent surface oxygenation is compared with continuous surface oxygenation during hypothermic machine perfusion<br>* Other names: feasibility of bubble and surface oxygenation applied to the LifePort Kidney Transporter (Organ Recovery Systems, Diegem, Belgium);|
| Active Comparator: C-HMPO2<br>continuous surface oxygenation during HMP (surface oxygenation during the whole machine preservation period included organ transport) | Drug: Oxygen<br>* Active oxygenation during hypothermic machine perfusion by bubble and surface oxygenation. Intermittent surface oxygenation is compared with continuous surface oxygenation during hypothermic machine perfusion<br>* Other names: feasibility of bubble and surface oxygenation applied to the LifePort Kidney Transporter (Organ Recovery Systems, Diegem, Belgium);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional delayed graft function | defined as the absence of a decrease in the serum creatinine level of at least 10% per day for at least 3 consecutive days in the first 7 days after transplantation (not including patients in whom acute rejection of calcineurin inhibitor toxicity is proven on biopsy) | first 7 days after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for dialysis after transplantation | Number of dialysis sessions after transplantation | 0-30 days after transplantation | 
| Delayed graft function | defined as the need for dialysis in the first 7 days after transplantation and preceding the return of kidney function | first 7 days after transplantation | 
| Serum creatinine reduction ratio | alternative definition of DGF= CRR2 < or = 30% | Day 1-2 after transplantation | 
| Graft survival | Functional kidney graft at 7 days, 3, 6, and 12 months | From 1-365 days after transplantation | 
| Patient survival (censored and uncensored for death) | Patient survival at 7 days, 3, 6, and 12 months | From 1-365 days after transplantation | 
| Glomerular filtration rate at 1 year after transplantation | 24-hour creatinine clearance | At 1 year after transplantation (window 30 days) | 
| Estimated glomerular filtration rate | eGFR defined by the CKD-EPI equation (Chronic Kidney Disease Epidemiology Collaboration) at 3, 6 and 12 months after transplantation | At 3, 6, and 12 months after transplantation with window of 10 days | 
| Primary non-function | defined as the continued need for dialysis at 3 months after transplantation | Until 3 months after transplantation | 
| Biopsy-proven acute rejection | Biopsy-proven acute rejection during the 1 year after transplantation | Until 1 year after transplantation with window of 10 days | 
| Metabolic analysis on kidney preservation tissue | Metabolic analysis by 1D proton NMR (e.g., succinate, lactate, acetate, formate, hypoxanthine) on a tissue sample taken before (= baseline) and at the end of the preservation period before transplantation of the kidney | Baseline and pre-surgery | 
| Metabolic analysis on kidney preservation tissue | Metabolic analysis by liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS) (succinate, glutamate, lactate, ATP, ADP, AMP, NADH, NAD+) on a tissue sample taken before (= baseline) and at the end of the preservation period before transplantation of the kidney | Baseline and pre-surgery | 
| Metabolic analysis on preservation fluid | Metabolic analysis by 1D proton NMR and fluorescence on a perfusion fluid sample taken before (= baseline) and at the end of the preservation period before transplantation of the kidney | Baseline and pre-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bubble and surface oxygenation, Hypothermic oxygenated machine perfusion, Kidney preservation