A prospective, randomized, single-blind, multicentre, phase III study on organ preservation with Custodiol-N solution compared with Custodiol® solution in organ transplantation (kidney, liver and pancreas)

Abstract

Background: Organ preservation before transplantation is still a challenge. Both the University of Wisconsin and Bretschneider's histidine-tryptophan-ketoglutarate (HTK; Custodiol®) solution are standard for liver, kidney and pancreas preservation. Organ preservation with both solutions is comparable; recently, however, Custodiol® solution has been modified to Custodiol-N according to the needs of today. Thus, our study was defined to study its effect in clinical transplantation. Methods: Patients undergoing kidney transplantation (n = 412) (including approximately 30 combined kidney-pancreas) or liver transplantation (n = 202) receive grafts that have been cold stored in either Custodiol® or Custodiol-N to demonstrate noninferiority of Custodiol-N regarding both graft function and graft injury after transplantation. Discussion: Preclinical data have clearly shown that Custodiol-N is superior to Custodiol® in cold static organ preservation via mechanisms including inhibition of hypoxic cell injury, cold-induced cell injury and avoidance of adverse effects during warm exposure to the solution. Further clinical safety data on Custodiol-N for cardioplegia are available. Thus, this study was designed to compare Custodiol® with Custodiol-N for the first time in a prospective, randomized, single-blinded, multicentre, phase III clinical transplantation trial.

HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution—A Promising New Tool in Solid Organ Preservation

“…HTK-N has been successfully used in two animal models of DCD liver [ 38 ] and kidney donation [ 67 ]. However, the available clinical data are limited, and DCD organs are excluded in the current multicenter clinical trial on HTK-N in kidney, liver and pancreas transplantation [ 64 ]. Parallel to the increased utilization of DCD organs is rise of machine perfusion in solid organ transplantation [ 5 ].…”

“…A prospective, randomized, single blind multicenter phase III study currently aims to demonstrate non-inferiority of graft preservation with HTK-N compared with HTK [64]. The study focuses on graft function and injury after transplantation of kidney, liver or combined kidney-pancreas.…”

Custodiol-N Is Superior to Custodiol® Solution in Experimental Rat Uterus Preservation

“…Based on literature, modulation of the solution used for uterus graft static cold storage (SCS) could prevent ROS formation with resulting in reduced cell damage [17]. On the basis of Custodiol ® solution, the novel Custodiol-N solution was developed and supplemented with glycine and alanine to inhibit formation of hypoxia-induced plasma membrane pores and fortified with iron chelators, including deferoxamine and LK-614, to inhibit cold-induced cell injury as well as L-arginine to decrease microcirculatory disturbances [26,27]. Moreover, mannitol has been replaced by sucrose.…”

“…The complete composition of the preservation solution is compiled in Table 1. In previous experiments, Custodiol-N proved to be superior to Custodiol ® solution concerning inhibition of hypoxic cell injury and cold-induced cell injury [26,[28][29][30]. An ongoing prospective, randomized, single blind, multicenter, phase III comparison study intends to demonstrate non-inferiority of Custodiol-N against Custodiol ® in kidney, combined kidney-pancreas and liver transplantation (ClinicalTrials.gov Identifier: NCT03627013) [21].…”

“…However, currently, no studies using the novel Custodiol-N for preserving the uterus were published. 2 2 2 Arginine -3 3 Alanine -5 5 Sucrose -33 33 Mannitol 30 --Glycine -10 10 Deferoxamine --0.025 LK-615 --0.0075 Data modified from Kniepeiss et al [26]. Custodiol-N base solution is Custodiol-N without iron chelators, deferoxamine, and LK-615.…”