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Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts

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ClinicalTrials.gov Identifier: NCT01317342
Recruitment Status : Completed
First Posted : March 17, 2011
Last Update Posted : March 25, 2021
Sponsor:
Information provided by (Responsible Party):
University of Zurich

Brief 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.


Condition or disease Intervention/treatment Phase
Hepatocellular Injury Device: Hypothermic oxygenated perfusion (HOPE) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 179 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Multicenter Study on the Effects of Hypothermic Oxygenated Perfusion (HOPE) on Human Liver Grafts Before Transplantation
Study Start Date : April 2015
Actual Primary Completion Date : August 30, 2020
Actual Study Completion Date : August 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Hypothermic oxygenated perfusion (HOPE)
Application of HOPE for 1 hour
Device: Hypothermic oxygenated perfusion (HOPE)
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

No Intervention: Control group: no intervention
Conventional cold storage (IGL-1)



Primary Outcome Measures :
  1. major complications after liver transplantation [ Time Frame: During the first year postoperatively ]
    post transplant complication Clavien >= III within 1 year after transplant


Secondary Outcome Measures :
  1. Laboratory parameters post transplant [ Time Frame: during first week, & 3,6,9,12 months ]
    Serum concentrations of bilirubin, AST, ALT, INR; Factor V

  2. Cholangiopathy [ Time Frame: during 12 months after transplant ]
    Biliary complications

  3. hospital stay, ICU stay [ Time Frame: during 12 months after transplant ]
    length of hospital and ICU stay after liver transplantation

  4. Patient and graft survival [ Time Frame: during 12 months after transplant ]
    one year patient and graft survival



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (≥18 years) patients with acute liver failure or liver cirrhosis (CHILD A, B or C) and/ or malignant liver tumors requiring liver transplantation
  • Whole liver graft
  • Signed informed consent

Exclusion Criteria:

  • Split graft
  • Living donor liver transplantation
  • Grafts donated after cardiac arrest (DCD grafts)
  • Domino transplantation
  • Combined liver transplant
  • Cold storage > 15h
  • acute and unexpected medical contraindication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01317342


Locations
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Switzerland
University Hospital of Zurich
Zurich, Switzerland, 8091
University of Zurich
Zurich, Switzerland, 8091
Sponsors and Collaborators
University of Zurich
Investigators
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Principal Investigator: Philipp Dutkowski Department of Surgery and Transplantation, University Hospital Zurich
Publications:
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Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01317342    
Other Study ID Numbers: 2011-0079
First Posted: March 17, 2011    Key Record Dates
Last Update Posted: March 25, 2021
Last Verified: March 2021
Keywords provided by University of Zurich:
liver transplantation
machine liver perfusion
extended criteria liver grafts
donation after cardiac death
hypothermic machine liver perfusion
liver reperfusion injury
Additional relevant MeSH terms:
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Hypothermia
Body Temperature Changes