Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts
Condition: Hepatocellular Injury
MeSH terms: Hypothermia
Study type: Interventional

Summary: 
      The purpose of this study is, in a randomized trial, to test a newly developed machine
      perfusion technique of human liver allografts before transplantation.

      Ischemia-reperfusion injury is universal in organ transplantation and leads to varying
      degrees of graft dysfunction. Despite this fact, the preservation method in organ
      transplantation has been left unchanged for many years and remains simple static cold
      storage. Given the scarce donor supply, an increasing number of so called marginal or
      extended criteria donor organs have been used for liver transplantation, grafts which were
      previously rarely considered. In addition, allocation policy has changed in many countries,
      and livers are currently often distributed by the severity of the recipient's disease. As a
      result, transplant candidates present sicker, with higher MELD (Model for end stage liver
      disease) scores, at the time of transplant,and the risk of graft dysfunction or even failure
      due to reperfusion injury is high after the use of marginal livers in sick recipients.

      Machine liver perfusion techniques have been significantly improved during the past decade to
      decrease reperfusion injury, and a number of promising results show beneficial effects in
      various animal transplant models by either normothermic or hypothermic oxygenated continuous
      liver perfusion. These techniques generally require machine liver perfusion immediately after
      organ procurement. However, continuous perfusion has several drawbacks, including major
      logistic efforts and risk of organ damage during perfusion and transport.

      Our group, therefore, focused on the practicability of machine liver perfusion. We developed
      an endischemic hypothermic oxygenated perfusion (HOPE) concept through the portal vein only.
      This technique can be easily applied in the operation room shortly before transplantation of
      the recipient, thus after organ transport and back table preparation.

      Recently, the beneficial effect of a similar approach has been confirmed in human liver
      grafts by a phase I non randomized trial. These results prove feasibility and safety of an
      endischemic hypothermic machine perfusion approach and warrant further randomized studies.
    

Detailed description: 
      The study consists on two groups, a perfusion group and a control group. Patients on the
      waiting list for liver transplantation with proven written consent will be recruited and
      randomized during organ procurement. Randomization will be performed by computer (secutrial).
      Perfusion will be started in the operation room after regular organ procurement, transport
      and back table preparation. The perfusion procedure will not delay the implantation due to
      the fact that recipient hepatectomy usually takes 2 hours. During this procedure, hypothermic
      oxygenated perfusion (HOPE group) for one hour will be performed vs continued cold storage
      (Control group).

      We will use commercially available and approved IGL solution (Institut George Lopez) as
      perfusate for machine perfusion.

      Subjects will be followed for one year after transplantation.

      10 European centers are participating in this study, Randomization is stratified by center.
    

Intervention name(s): Hypothermic oxygenated perfusion (HOPE)
Intervention type(s): Device
Intervention description(s): Application of HOPE for 1 hour, perfusion rate 150-300 ml/min, pressure controlled, perfusion pressure < 3 mm Hg, perfusion route portal vein, recirculating system, perfusion volume 2 L, perfusate Institute George Lopez solution (IGL-1), perfusate temperature 4-6 °C, perfusate oxygenation 150-200 mm Hg
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: liver transplantation; machine liver perfusion; extended criteria liver grafts; donation after cardiac death; hypothermic machine liver perfusion; liver reperfusion injury