Dual Hypothermic Oxygenated Perfusion of DCD Liver Grafts in Preventing Biliary Complications After Transplantation
Status:
Completed
Trial end date:
2020-01-01
Target enrollment:
Participant gender:
Summary
Rationale: Recent publications report good results of controlled donation after circulatory
death (DCD) Maastricht category III liver transplantation when strict donor-recipient
matching is applied and ischemia times are kept to a minimum. However a major concern remains
the high rate of biliary complications after transplantation of DCD livers. Non-anastomotic
biliary strictures (NAS) occur in 29% of patients receiving a DCD graft whereas the incidence
of NAS in recipients of donation after brain death (DBD) liver grafts is 11%. NAS are
associated with higher morbidity and increased cost of liver transplantation. Injury to the
biliary epithelium and the peribiliary vascular plexus occurring during donor warm ischemia
and static cold storage (SCS) has been identified as a major risk factor for development of
NAS. Machine perfusion has been proposed as an alternative strategy for organ preservation,
offering the opportunity to improve the quality of the organ by providing oxygen to the
graft. Experimental studies have shown that end-ischemic dual hypothermic oxygenated machine
perfusion (DHOPE) helps liver grafts to recover from ischemia by restoring mitochondrial
function. Moreover, DHOPE has been shown to provide better preservation of peribiliary
vascular plexus of the bile ducts, which could be an important step forward in reducing the
incidence of NAS after transplantation.
Objective: To study the efficacy of end-ischemic DHOPE in reducing the incidence of NAS
within six months after controlled DCD (Maastricht category III) liver transplantation.
Study design: An international, multicenter, prospective, randomized, controlled,
interventional, clinical trial with a two parallel arm approach (treatment/control).
Study population: Adult patients (≥18 yrs old) undergoing a liver transplantation with a
liver graft procured from a controlled DCD donor (Maastricht category III) with a body weight
≥40 kg.
Intervention: In the intervention group liver grafts will be subjected to two hours of
hypothermic, oxygenated perfusion at the end of SCS and before implantation. In the control
group donor liver grafts will be preserved in accordance to standard practice by SCS only.
Main study parameters/endpoints: The incidence and severity of symptomatic NAS as diagnosed
by an Adjudication committee (who are blinded for the group assignment) by means of magnetic
resonance cholangiopancreatography (MRCP).
Phase:
Phase 3
Details
Lead Sponsor:
Robert J. Porte
Collaborators:
Erasmus Medical Center King's College Hospital NHS Trust Leiden University Medical Center Universitaire Ziekenhuizen Leuven University Hospital, Ghent