Evaluation of a Marine OXYgen Carrier for Organ Preservation

Study Overview
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Brief Summary
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Preventing ischemia/reperfusion injuries (IRIs) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRIs is delayed graft function (DGF). The medical device HEMO2life®, an oxygen carrier developed by the Hemarina French Company, is a natural extracellular hemoglobin (Hb) isolated from the marine lugworm Arenicola marina. This biopolymer of high molecular weight ( 3,600 kDa) has a large oxygen binding capacity, carrying up to 156 oxygen molecules when saturated (4 for human Hb). It releases oxygen according to a simple gradient and exhibits an intrinsic superoxide dismutase-like activity preventing both the occurrence of potentially harmful heme-protein-associated free radical species and the release of Hb degradation products. Recently a safety study in 60 renal grafts using HEMO2life® as additive to organ preservation solution (Oxyop study, NCT02652520) was completed, that confirmed that the use of HEMO2life® is safe for patients and grafts. In the Oxyop study, even if the protocol was not designed to show a benefit of the use of HEMO2life®, significantly less delayed graft function (DGF) and a shorter renal function recovery was observed. The present research focuses on the efficacy of HEMO2life®, which is an oxygen carrier added in preservation solution in kidney transplantation.

Official Title
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Evaluation of a Marine OXYgen Carrier for Organ Preservation : a Multicenter Randomized Study Evaluating the Efficacy of HEMO2life® Versus Standard of Care in Renal Transplantation

Conditions
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End Stage Renal Diseases

Intervention / Treatment
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* Procedure: Kidney transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Kidney graft: Any pair of kidneys retrieved in an adult donor in one of first line participating centers. Any pair of kidneys from a deceased donor after brain or cardiac death For Patient: Male or female renal allograft recipients at least 18 years old Patient who signed an inform consent form Patient receiving one graft from an included pair of kidneys Exclusion criteria : For kidney : Graft from a living donor Graft dedicated to a multi-organ transplantation or 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEMO2life<br>HEMO2life® will be used for ex vivo graft preservation at the dose of 1g per liter of preservation solution. | Procedure: Kidney transplant<br>* Organ preserved in preservation solution<br>|
| Other: Control<br>Organ preserved in preservation solution routinely used according to the local practice | Procedure: Kidney transplant<br>* Organ preserved in preservation solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of HEMO2life® as an additive to standard organ preservation solution to prevent delayed graft function following renal transplantation. | Delayed graft function defined as the requirement for dialysis during the first week after transplantation will be compared as per the confirmatory testing strategy | From day 0 to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess and compare graft and patient survival in the two groups. | Graft and patient survival at one year | From month 0 to month 12 | 
| Efficacy of HEMO2life® on renal parameters compared with standard of care | Evaluation using DGF assessed with alternative definitions: more than one dialysis session, need for dialysis except for hyperkaliemia or overhydration reason, time to reach a creatinine value of 250 µmol/l, DGF duration and using Renal function (creatinine value and eGFR) | From month 0 to month 12 | 
| Efficacy in specific populations depending on type of donors and the type of preservation solution. | Rate of primary non function | From month 0 to month 12 | 
| Evaluate the impact of HEMO2Life® on the degree and progression of interstitial fibrosis on the pre-implantation and 3 month biopsies | Rate of biopsy-proven acute rejection at one year | biopsies pre-implantation and month 3 | 
| Evaluate the impact of HEMO2life® on quality of life following renal transplant at Month-1, 3 and 12. | Quality of life assess using the generic self-administered questionnaire EuroQol-5 Dimensions (EQ-5D) and a specific questionnaire for renal transplant recipients in the French language: the ReTransQol (RTQ) [0-100]. For RTQ, higher score mean a better outcome. | From Day 0 to month 12 | 
| Safety profile of HEMO2life® post transplant | Safety profile of HEMO2life® post transplant based on 3 analysis : graft safety, recipient safety, graft function | From organ preservation to month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplantation, Organ preservation