Dual Hypothermic Oxygenated Perfusion of DCD Liver Grafts in Preventing Biliary Complications After Transplantation

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).

Conditions

• Liver Failure
• End Stage Liver Disease
• Biliary Tract Diseases

Interventions

PROCEDURE

Dual hypothermic oxygenated perfusion

Dual hypothermic oxygenated perfusion using the Liver Assist

DEVICE

Liver Assist®

The Liver Assist® is the device used to give the intervention dual hypothermic perfusion.

PROCEDURE

Perfusion fluid

The perfusion fluid is Belzer machine perfusion solution University of Wisconsin (Bridge-to-Life, Ltd., Northbrook, IL).

DRUG

Glutathione

Glutathione in a dosage of 3 mmol/ is added to the perfusion fluid according to the intention of use of the perfusion fluid.

Sponsors & Collaborators

• Erasmus Medical Center

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• Universitaire Ziekenhuizen KU Leuven

  collaborator OTHER

• University Hospital, Ghent

  collaborator OTHER

• King's College Hospital NHS Trust

  collaborator OTHER

• Robert J. Porte

  lead OTHER

Principal Investigators

• Robert J. Porte, MD PhD Prof · University Medical Center Groningen

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-01-31

Primary Completion

2020-01-31

Completion

2020-01-31

Countries

• Belgium
• Netherlands
• United Kingdom

Study Locations