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. 2023 May 1;24(1):302.
doi: 10.1186/s13063-023-07302-3.

Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial

Yannick Le Meur  1   2 , Emmanuel Nowak  3   4 , Benoit Barrou  5 , Antoine Thierry  6 , Lionel Badet  7 , Matthias Buchler  8 , Jean-Philippe Rerolle  9 , Leonard Golbin  10 , Agnès Duveau  11 , Jacques Dantal  12 , Pierre Merville  13 , Nassim Kamar  14 , Leïla Demini  15 , Franck Zal  15
Affiliations

Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial

Yannick Le Meur et al. Trials. .

Abstract

Background: Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts.

Methods: OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation.

Discussion: The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation.

Trial registration: ClinicalTrials.gov, ID: NCT04181710 . registered on November 29, 2019.

Keywords: Clinical trial; Delayed Graft Function (DGF); HEMO2life®; Ischemia–Reperfusion Injury (IRI); Kidney IRI; Transplantation.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships that may be considered potential competing interests: Franck Zal is the founder of and holds stock in HEMARINA, the company that produces M101. Leila Demini is a collaborator of HEMARINA and does not have HEMARINA stock. Yannick Le Meur received consulting fees from HEMARINA. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the trial design. H2L: HEMO2life®. SOC: Standard of Care
Fig. 2
Fig. 2
The flowchart depicts the entire confirmatory testing strategy. This implementation will allow the investigator to make inferences on the overall population and/or on a prespecified subgroup (cold storage). The methodology developed by Alosh and Huque [31], which requires meeting some consistency constraints as a prerequisite for testing the next hypothesis, will be used. This proposed methodology requires first testing global efficacy at a reduced alpha level α0. Based on this result and on a consistency constraint within the complementary subgroup (machine perfusion), the efficacy for the cold storage subgroup may also be tested. The variability (standard deviation) is assumed to be similar in the two subgroups. Therefore, the significance level for the subgroup of interest αS is derived from the proportions of the subgroups, which are expected to be balanced within the global sample, i.e., 50% cold storage and 50% machine perfusion. This yields an αS equal to 0.02633 (two-sided) to control for the familywise error rate (FWER) strongly
See this image and copyright information in PMC

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