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

Abstract

Background: 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). 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.

Methods: This 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.

Discussion: DHOPE 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 registration: The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283 .

Keywords: Adult; Cost; Donation after circulatory death; Incidence; Ischemic type biliary lesions; Survival.

Conflict of interest statement

Ethics approval and consent to participate

This trial will be conducted in accordance with the principles of the Declaration of Helsinki and as stated in Good Clinical Practice and in the laws governing human research in the Netherlands, Belgium and United Kingdom. The MEC of the University Medical Center Groningen and local ethical committees of all participating centers have approved this protocol. This protocol was endorsed by the board of directors of each participating hospital prior to the inclusion of subjects at the respective hospital. Informed consent will be obtained from each participating patient in oral and written form prior to randomization.

Ethical committees and study reference numbers:

1. Medisch Ethische Toetsingscommissie UMC Groningen METc 2015/131

2. Medisch Ethische Toetsings Commissie Erasmus MC MEC-2016-090

3. Commissie Medische Ethiek LUMC P16.325

4. Commissie Medische Ethiek UZ KU Leuven B322201629530

5. Commissie voor Medische Ethiek UZ Ghent 2016/1582

6. London – Surrey Research Ethics Committee 17/LO/2011

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Flow chart of study procedures. Abbreviations: DHOPE, dual hypothermic oxygenated machine perfusion