Peritransplant eculizumab does not prevent delayed graft function in deceased donor kidney transplant recipients: Results of two randomized controlled pilot trials.Schroppel, B., Akain, E. et al. (2019).
American Journal of Transplantation [record in progress].
This report aimed to explore the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent delayed graft function (DGF) in recipients of deceased donor kidney transplants in two, randomized controlled trials: the pilot study and multicentre study.
Patients in the pilot study were randomized to receive either saline placebo or Ecu at a dose of 1200mg, prior to transplant surgery. Patients in the Multicenter study were randomized to either saline placebo or two doses of Ecu (an initial dose of 1200mg and second dose of 900mg after 12-24hrs of the initial dose). All patients were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and followed for 6 months.
8 participants were recruited for the pilot study. The inclusion criteria for participation was ≥18 years of age, recipient of a primary kidney transplant from a deceased, “standard criteria donor” (SCD) with cold ischemia time (CIT) of >24 hours, or from an “extended criteria donor” (ECD) kidney. A total of 19 participants from the multicenter trial were included; these subjects were eligible on the basis of being ≥18 years of age, the recipient of a primary, HLA‐mismatched, kidney transplant from a deceased, SCD kidney with CIT of 18 to 40 hours, or from an ECD kidney.
The primary outcome of the pilot study was the composite of DGF alongside slow graft function (SGF). DGF was defined by at least one dialysis treatment during the first 7 days after transplantation. Whereas, for the multicenter study, the primary endpoint was the need for at least one dialysis treatment during the first 7 days after transplantation, regardless of cause.
This is a pooled analysis of two small (unpublished) double-blinded, randomised controlled trials evaluating the efficacy and safety of anti-C5 monoclonal antibody eculizumab (Ecu) to reduce the rate of delayed graft function (DGF) in adult recipients of standard criteria donor or extended criteria donor kidneys. A small single-centre pilot study included 8 participants and was followed by a multicentre study including 19 patients, which was terminated early as the results of the similar PROTECT study showed no efficacy for Ecu in reducing DGF. The research pharmacist prepared the Ecu infusion and used a web-based randomisation application to randomise patients to Ecu or saline. Infusion bags were covered by the pharmacist to ensure blinding of all study personnel and participants throughout the study. Power analysis showed that 48 patients were needed to providing 50% power to detect a reduction in DGF from 40% to 17.5% (the goal of the multicentre study was justify a subsequent larger study). Data were analysed according to the intention to treat principle which included all randomised patients who received the study drug. Data were analysed for each trial separately and a pooled analysis of both trials was performed despite some differences in the design of the two studies and definition of DGF. The small studies and the pooled analysis did not find significant differences between the Ecu and control arms in terms of DGF and adverse events, which is similar to the results of the PROTECT study.
ClinicalTrials.gov - NCT01403389 and NCT01919346