Administrative information
Title {1} | Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: Study protocol for a multicenter randomized trial |
---|---|
Trial registration {2a and 2b} | ClinicalTrials.gov, ID: NCT04181710. registered on November 29, 2019 |
Protocol version {3} | February 22 nd, 2022, Version 3 |
Funding {4} | This study was supported by a grant from the French Ministry of Health (PHRCN 2018), and was cosponsored by HEMARINA |
Author details {5a} | 1Department of Nephrology, Hôpital de la Cavale Blanche, CHRU de Brest, Brest, France. 2Centre d'Investigation Clinique INSERM CIC 1412, Hôpital de la Cavale Blanche, CHRU de Brest, Brest, France, 3Public Agency for Clinical Research and Innovation (DRCI), Brest University Hospital, Brest, France, 4Department of Urology, Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris AP-HP, Hôpitaux Universitaire de la Pitié Salpétrière-Charles Foix, Paris, France. 5Department of Nephrology, CHU la Milétrie, Poitiers, France. 6Department of Urology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 7Department of Urology, Hôpital Bretonneau, CHRU de Tours, Tours, France. 8Department of Nephrology, CHU Dupuytren, Limoges, France. 9Department of Nephrology, CHU de Rennes, France. 10Department of Nephrology and Urology, CHU d’Angers, Angers, France. 11Department of Nephrology and Urology, CHU de Nantes, Nantes, France. 12Department of Nephrology and Urology, Hôpital Pellegrin, Bordeaux, France. 13Department of Nephrology and Urology, Hôpital Rangueil, CHU de Toulouse, Toulouse, France. 14HEMARINA, Aéropôle Centre, Morlaix, France |
Name and contact information for the trial sponsor {5b} | Brest University Hospital Direction de la Recherche et de l’Innovation Avenue Foch 29,609 BREST CEDEX—FRANCE Phone: + 33.2.98.22.39.79 Fax: + 33.2.98.22.31.83 |
Role of sponsor {5c} | Monitoring of the collected data and screening forms in each participating centre will be carried out by the sponsor. The funding source has no influence on trial design, trial conduct, data handling, data analysis or writing of the manuscript |
Introduction
Background and rationale {6a}
Objectives {7}
-
To quantify the efficacy of HEMO2life® used as an additive to standard organ preservation solution to prevent DGF following renal transplantation.
-
To assess and compare graft and patient survival in the two groups (standard of care versus HEMO2life®)
-
To assess the efficacy of HEMO2life® on renal parameters compared with the standard of care.
-
To assess efficacy in specific populations with different donor types and preservation method (standard donors, ECD, DCD, SCS, machine perfusion, different perfusion solutions).
-
To evaluate the impact of HEMO2life® on the degree and progression of interstitial fibrosis before implantation and in 3-month biopsies.
-
To assess the safety profile of HEMO2life® for the graft and the graft recipient.
Trial design {8}
Methods: Participants, interventions and outcomes
Study setting {9}
Eligibility criteria {10}
Inclusion criteria
-
any pair of kidneys retrieved from an adult donor in one of the first-line participating centers.
-
any pair of kidneys from a deceased donor after brain or cardiac death (DBD or DCD) who was not opposed of the use of its donation to help scientific research (checking of the French National Registry for Refusal of Organ Donation).
-
male or female renal allograft recipient at least 18 years old.
-
patient who signed an informed consent form.
-
patient receiving one graft from an included pair of kidneys.
Exclusion criteria
-
graft from a living donor.
-
graft dedicated to multiorgan transplantation or dual kidney transplantation.
-
donor registered in the French National Registry for Refusal of Organ Donation
-
age less than 18 years.
-
refusal to participate in the study.
Who will take informed consent? {26a}
Donor
Recipient
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
-
Primary outcome: The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation.
-
Secondary outcomes: Efficacy and safety secondary outcomes will be collected.
-
rate of PNF.
-
graft and patient survival at one year.
-
rate of biopsy-proven acute rejection at one year.
-
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, and number of dialysis sessions.
-
renal function (creatinine value and estimated glomerular filtration rate (eGFR)) at Days 7, 14, and 30 and months 3 and 12; areas under the concentration curves (AUCs) of creatinine and eGFR from D0 to D30.
-
protocol biopsy analysis (preimplantation and at month 3) in a subgroup of 100 patients per group: A) comparison of the chronic scores of tubule-interstitial damage according to the Banff classification [29]: tubular atrophy (ct score ranging from 0 to 3) and chronic interstitial fibrosis (ci score ranging from 0 to 3); and of vascular damage: fibrous intimal thickening (cv score ranging from 0 to 3) and arteriolar hyalinosis (ah score ranging from 0 to 3). B) Analysis of interstitial fibrosis using automated quantitative image analysis (Institut Pasteur-France) and comparison of the progression of interstitial fibrosis in a subgroup of 100 patients per group.
-
quality of life: at 1, 3 and 12 months, using the generic self-administered questionnaire EQ-5D and a specific questionnaire for renal transplant recipients in the French language: the ReTransQol (RTQ) [30].
Safety
Participant timeline {13}
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: Blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
-
Signed informed consent
-
Compliance of the study’s protocol and its described procedures
-
QC of the collected data into the e-CRF: accuracy, missing data, consistency between these data and those of “source” (medical files, original of the laboratory results, etc.)
Confidentiality {27}
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
-
All complete and concordant (according to the type of conservation: cold storage or perfusion machine) randomized pairs fulfilling the inclusion criteria with no exclusion criterion.
-
Preemptive grafts will be excluded
-
Randomized pairs who do not receive HEMO2life® will be excluded, provided that HEMO2life® cancellation is not related to graft function.
-
All randomized grafts fulfilling the inclusion criteria and no exclusion criterion will be included.
-
Preemptive grafts will be excluded
-
Randomized pairs who do not receive HEMO2life® will be excluded provided that HEMO2life® cancellation is not related to graft function.