Dual Hypothermic Oxygenated Perfusion of DCD Liver Grafts in Preventing Biliary Complications After Transplantation (DHOPE-DCD)

Robert J. Porte

Status and phase: Completed; Phase 3

Conditions: Liver Failure; End Stage Liver Disease; Biliary Tract Diseases

Treatments: Drug: Glutathione; Device: Liver Assist®; Procedure: Dual hypothermic oxygenated perfusion; Procedure: Perfusion fluid

Study type: Interventional

Funder types: Other

Identifiers

NCT02584283

DHOPE-DCD Trial

Details and patient eligibility

About

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).

Enrollment: 157 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients (≥ 18 years old)
• Signed informed consent
• Willing and able to attend follow-up examinations
• Donor liver graft from a controlled donation after circulatory death (Maastricht category III)
• Donors with a body weight ≥40 kg

Exclusion criteria

• Simultaneous participation in another clinical trial that might possibly influence this trial
• Mental conditions rendering the subject incapable to understand the nature, scope and consequences of the trial
• Listed for liver transplantation due to fulminant liver failure or retransplantation because of primary non-function
• Recipient positive test for HIV
• Donor positive for HIV antigen, hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody
• Simultaneous transplantation of another organ
• Patients with contra-indications for MRCP (i.e. pacemaker)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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157 participants in 2 patient groups

Dual hypothermic oxygenated perfusion

Experimental group

Description:

The liver is procured with a segment of supratruncal aorta. The intervention is restricted to the liver graft after arrival in the transplant center and before implantation. The donor liver is subjected to 2 hours of hypothermic oxygenated perfusion via the portal vein and the supratruncal aorta applied by the Liver Assist®. Before perfusion, the liver is flushed via the portal vein with 1 L Belzer machine perfusion solution. The perfusion is pressure controlled and set to a mean of 25 mmHg (arterial) and 5 mm Hg (portal). The perfusion fluid is 4 L Belzer machine perfusion solution with additional 3 mmol/L glutathione. The perfusion fluid is 12°C, when the temperature is set at 10°C. The oxygen flow is set at 0.5 mL/min of 100% oxygen on each of the two membrane oxygenators.

Treatment:

Device: Liver Assist®

Procedure: Dual hypothermic oxygenated perfusion

Drug: Glutathione

Procedure: Perfusion fluid

Care as usual

No Intervention group

Description:

The donor liver is procured with a segment of 5 cm circular supratruncal aorta left attached to the coeliac trunc. The patients randomized to the control group will receive a liver graft preserved by conventional SCS without any further intervention.