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Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts

This study is currently recruiting participants.
Verified September 2011 by University of Zurich
Sponsor:
Information provided by (Responsible Party):
University of Zurich
ClinicalTrials.gov Identifier:
NCT01317342
First received: March 10, 2011
Last updated: September 23, 2011
Last verified: September 2011
History of Changes
  Purpose

The purpose of this study is, in a phase II 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 Intervention Phase
Hepatocellular Injury
 Device: Hypothermic oxygenated perfusion (HOPE)
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blinded Randomized Study on the Effects of Hypothermic Oxygenated Perfusion (HOPE) on Human Liver Grafts Before Transplantation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Postoperative peak ALT levels in blood serum (area under the curve) [ Time Frame: During the first week postoperatively ] [ Designated as safety issue: No ]
    Serum ALT (Alanin Aminotransferase)


Secondary Outcome Measures:
  • Postoperative outcome (Dindo/Clavien classification) [ Time Frame: Subjects will be followed for one year postoperatively ] [ Designated as safety issue: Yes ]
  • Hospital- and ICU stay [ Time Frame: postoperative course ] [ Designated as safety issue: No ]
    Duration of hopitalization and ICU stay

  • Inflammatory response and reperfusion injury [ Time Frame: before and after preservation, during reperfusion (0-3 hr) after liver implantation ] [ Designated as safety issue: No ]
    Liver samples taken after procurement, before HOPE, after HOPE or after cold storage, respectively, and at the end of implantation before closure of the abdomen to evaluate the amount of ischemia reperfusion (I/R) injury.

  • Patient and graft survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    one year patient and graft survival

  • outcome (Clavien/Dindo classification)in terms of extended criteria donor grafts [ Time Frame: 1 year postoperatively ] [ Designated as safety issue: No ]
    Subgroup analysis


Estimated Enrollment: 70
Study Start Date: September 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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 (www.randomizer.at). 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.

Interim Analysis:

Interim analysis will take be performed for safety and ethical purposes. As soon as we reach 20 patients per randomized group, data will be analyzed by an independent Data Monitoring Committee. The trial will be immediately stopped if one of the following is satisfied:

  1. Efficacy: If the mean ALT levels are statistically significantly higher (p<0.001, Student's T-test) in the HOPE group when compared to the Control group.
  2. Safety: If the proportion of complications (Grade ≥ III) is statistically significantly higher (p<0.05, Fischer's Exact 2-sided Test) in the HOPE group when compared to the Control group.

Subgroup analysis:

A subgroup analysis will be performed in terms of adjusting to extended criteria donor grafts.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (more than 18 years) patients with liver cirrhosis (CHILD B or C) and/ or malignant liver tumors requiring liver transplantation

Exclusion Criteria:

  • Graft macrosteatosis > 60 %,
  • Donor AST (serum) > 300 U/L
  • Donor ALT (serum) > 200 U/l
  • split graft
  • living donor liver grafts
  • hepatic encephalopathy of recipient
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01317342

Contacts
Contact: Philipp Dutkowski, Professor, MD 0041 44 255 4236 philipp.dutkowski@usz.ch

Locations
Switzerland
University Hospital of Zurich Not yet recruiting
Zurich, Switzerland, 8091
Contact: Philipp Dutkowski, PD, MD     0041 44 255 4236     philipp.dutkowski@usz.ch    
Contact: Michelle De Oliveira, MD     0041 44 255 3300     michelle.deoliveira@usz.ch    
Principal Investigator: Philipp Dutkowski, Professor, MD            
Sub-Investigator: Michelle De Oliveira, MD            
University of Zurich Recruiting
Zurich, Switzerland, 8091
Contact: Philipp Dutkowski, Professor     0041 44 255 4236     philipp.dutkowski@usz.ch    
Sponsors and Collaborators
University of Zurich
Investigators
Principal Investigator: Philipp Dutkowski, PD, MD Department of Surgery and Transplantation, University Hospital Zurich
  More Information

Publications:

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01317342     History of Changes
Other Study ID Numbers: 2011-0079
Study First Received: March 10, 2011
Last Updated: September 23, 2011
Health Authority: Switzerland: Federal Office of Public Health

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:
Hypothermia
Liver Diseases
Body Temperature Changes
Signs and Symptoms
Digestive System Diseases

ClinicalTrials.gov processed this record on May 23, 2013