Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial

Abstract

Background: Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF.

Methods: The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg-1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group).

Discussion: Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation.

Trial registration: ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016.

Keywords: Cyclosporine A; Delayed graft function; Kidney; Preconditioning; Transplantation.

Conflict of interest statement

Ethics approval and consent to participate

The study will be conducted in accordance with the Helsinski Declaration and the French laws and regulations (Code de la Santé Publique, article L.1121–1/Loi de Santé Publique n°2004–806 du 9 août 2004 relative à la politique de santé publique et ses décrets d’application du 27 août 2006) and the International Conference on Harmonization (ICH) E6 Guideline for Good Clinical Practice. Absence of opposition to research will be obtained from the next-of-kin of brain dead donors by the attending intensivist. Written informed consent (additional file) to analyze their data will be obtained from the recipients of the preconditioned kidneys by their attending nephrologist. A central ethic committee approved the study for all centers (comité de protection des personnes Sud-Est VI, Clermont-Ferrand, France) on 21 March 2017 with the registration number 2014–003544-12. The study was registered at Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Overview of enrollment, interventions and assessments of the Cis-A-rein study. DGF delayed graft function, SGF slow graft function