Prolonged dual hypothermic oxygenated machine preservation (DHOPE-PRO) in liver transplantation: study protocol for a stage 2, prospective, dual-arm, safety and feasibility clinical trial

Abstract

Introduction: End-ischaemic preservation of a donor liver by dual hypothermic oxygenated machine perfusion (DHOPE) for 2 hours prior to transplantation is sufficient to mitigate ischaemia-reperfusion damage and fully restore cellular energy levels. Clinical studies have shown beneficial outcomes after transplantation of liver grafts preserved by DHOPE compared with static cold storage. In addition to graft reconditioning, DHOPE may also be used to prolong preservation time, which could facilitate logistics for allocation and transplantation globally.

Methods and analysis: This is a prospective, pseudo-randomised, dual-arm, IDEAL-D (Idea, Development, Exploration, Assessment, Long term study-Framework for Devices) stage 2 clinical device trial designed to determine safety and feasibility of prolonged DHOPE (DHOPE-PRO). The end-time of the donor hepatectomy will determine whether the graft will be assigned to the intervention (16:00-3:59 hour) or to the control arm (4:00-15:59 hour). In total, 36 livers will be included in the study. Livers in the intervention group (n=18) will undergo DHOPE-PRO (≥4 hours) until implantation the following morning, whereas livers in the control group (n=18) will undergo regular DHOPE (2 hours) prior to implantation. The primary endpoint of this study is a composite of the occurrence of all (serious) adverse events during DHOPE and up to 30 days after liver transplantation.

Ethics and dissemination: The protocol was approved by the Medical Ethical Committee of Groningen, METc2020.126 in June 2020, and the study was registered in the Netherlands National Trial Registry (https://www.trialregister.nl/) prior to initiation.

Trial registration number: NL8740.

Keywords: clinical trials; liver; liver transplantation.

Figure 1

Flow chart of this study. DBD, donation after brain death; DCD, donation after circulatory death; DHOPE-PRO, prolonged dual hypothermic oxygenated machine perfusion; DHOPE-CON, regular dual hypothermic oxygenated machine perfusion; HBV, viral hepatitis B; HCV, viral hepatitis C; HU, high-urgency; MELD, model for end-stage liver disease.

Figure 2

Study design. AKI, acute kidney injury; CCI, Comprehensive Complications Index; DBD, donation after brain death; DCD, donation after circulatory death; DHOPE-PRO, prolonged dual hypothermic oxygenated machine perfusion; DHOPE-CON, regular dual hypothermic oxygenated machine perfusion; LT, liver transplantation; SADE, serious adverse device event; SAE, serious adverse event; SCS, static cold storage; UMCG, University Medical Centre Groningen.