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

• Published in: BMC gastroenterology Vol. 19; no. 1; p. 40
• Main Authors: van Rijn, Rianne, van den Berg, Aad P, Erdmann, Joris I, Heaton, Nigel, van Hoek, Bart, de Jonge, Jeroen, Leuvenink, Henri G D, Mahesh, Shekar V K, Mertens, Sarah, Monbaliu, Diethard, Muiesan, Paolo, Perera, M Thamara P R, Polak, Wojciech G, Rogiers, Xavier, Troisi, Roberto I, de Vries, Yvonne, Porte, Robert J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12-03-2019; BioMed Central; BMC
• Subjects: Adult; Analysis; Bile ducts; Brain death; Care and treatment; Cholestasis - prevention & control; Clinical trials; Cost; Cryopreservation; Death; Donation after circulatory death; Donations; Double-Blind Method; Endothelium; Gastroenterology; Humans; Hypothermia, Induced - methods; Incidence; Ischemia; Ischemic type biliary lesions; Kidneys; Liver; Liver transplantation; Liver Transplantation - adverse effects; Medical research; Mitochondria; Multicenter Studies as Topic; Organ Preservation - methods; Organ transplantation; Perfusion; Perfusion - methods; Postoperative Complications; Preservation; Prevention; Randomized Controlled Trials as Topic; Reperfusion; Reperfusion injury; Reperfusion Injury - prevention & control; Rodents; Stricture; Studies; Study Protocol; Surgery; Survival; Tissue and Organ Procurement - methods; Tissue donation; Tissue Donors; Transplants & implants; United States > US; Adult; Donation after circulatory death; Cost; Survival; Ischemic type biliary lesions; Incidence
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-019-0956-6

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.
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.
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.
The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283 .