Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial

Rianne Van Rijn,M Thamara P R Perera,Nigel Heaton,Wojciech G Polak,Diethard Monbaliu,Xavier Rogiers,Shekar V K Mahesh,Roberto I Troisi,Henri G D Leuvenink,Bart Van Hoek,Yvonne De Vries,Joris I Erdmann,Jeroen De Jonge,Robert J Porte,Sarah Mertens,Paolo Muiesan,Aad P Van Den Berg

doi:10.1186/s12876-019-0956-6

Abstract

BackgroundThe major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation.MethodsThis is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation.DiscussionDHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial.Trial registrationThe trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283.

Highlights

The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS)
We aim to reduce the incidence of NAS after DCD liver transplantation with dual hypothermic oxygenated machine perfusion (DHOPE) to the level observed after donation after brain death (DBD) liver transplantation
The major drawback of DCD, compared to DBD, is the inevitable period of warm ischemia which leads to the depletion of intracellular energy sources, such as adenosine triphosphate (ATP) as well as other metabolic perturbations causing cellular injury and dysfunction [39, 40]

Summary

Introduction

The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. Utilization of livers with suboptimal quality or so called “extended criteria” donors, such as older donors, donors with fatty livers and donation after circulatory death (DCD) donors, have reduced the organ deficit in recent years. The percentage of DCD donors in the USA has increased from 1.1% in 1995 to 11.2% in 2010 [2]. The percentage of unused grafts increased from 9% in 2004 to 28% in 2010 in the USA which is mainly attributed to the growing number of DCD donors [2]

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