Dual Hypothermic Oxygenated Perfusion of DCD Liver Grafts in Preventing Biliary Complications After Transplantation
Condition: Liver Failure; End Stage Liver Disease; Biliary Tract Diseases
MeSH terms: Liver Diseases; Liver Failure; End Stage Liver Disease; Biliary Tract Diseases
Study type: Interventional
Phase: Phase 3

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).
    


Intervention name(s): Dual hypothermic oxygenated perfusion; Liver Assist®; Perfusion fluid; Glutathione
Intervention type(s): Procedure; Device; Procedure; Drug
Intervention description(s): Dual hypothermic oxygenated perfusion using the Liver Assist; The Liver Assist® is the device used to give the intervention dual hypothermic perfusion.; The perfusion fluid is Belzer machine perfusion solution University of Wisconsin (Bridge-to-Life, Ltd., Northbrook, IL).; Glutathione in a dosage of 3 mmol/ is added to the perfusion fluid according to the intention of use of the perfusion fluid.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Liver Transplantation; Donation after Circulatory Death; Machine Perfusion