Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts
Study Details
Study Description
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 |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| 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) |
Outcome Measures
Primary Outcome Measures
- major complications after liver transplantation [During the first year postoperatively]
post transplant complication Clavien >= III within 1 year after transplant
Secondary Outcome Measures
- Laboratory parameters post transplant [during first week, & 3,6,9,12 months]
Serum concentrations of bilirubin, AST, ALT, INR; Factor V
- Cholangiopathy [during 12 months after transplant]
Biliary complications
- hospital stay, ICU stay [during 12 months after transplant]
length of hospital and ICU stay after liver transplantation
- Patient and graft survival [during 12 months after transplant]
one year patient and graft survival
Eligibility Criteria
Criteria
Inclusion Criteria:
- Adult (≥18 years) patients with acute liver failure or liver cirrhosis (CHILD A, B or
- and/ or malignant liver tumors requiring liver transplantation
-
Whole liver graft
-
Signed informed consent
Exclusion Criteria:
-
Split graft
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Living donor liver transplantation
-
Grafts donated after cardiac arrest (DCD grafts)
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Domino transplantation
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Combined liver transplant
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Cold storage > 15h
-
acute and unexpected medical contraindication
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital of Zurich | Zurich | Switzerland | 8091 | |
| 2 | University of Zurich | Zurich | Switzerland | 8091 |
Sponsors and Collaborators
- University of Zurich
Investigators
- Principal Investigator: Philipp Dutkowski, Department of Surgery and Transplantation, University Hospital Zurich
Study Documents (Full-Text)
None provided.More Information
Publications
- de Rougemont O, Breitenstein S, Leskosek B, Weber A, Graf R, Clavien PA, Dutkowski P. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg. 2009 Nov;250(5):674-83. doi: 10.1097/SLA.0b013e3181bcb1ee.
- Dutkowski P, de Rougemont O, Clavien PA. Machine perfusion for 'marginal' liver grafts. Am J Transplant. 2008 May;8(5):917-24. doi: 10.1111/j.1600-6143.2008.02165.x. Review.
- Dutkowski P, Furrer K, Tian Y, Graf R, Clavien PA. Novel short-term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor. Ann Surg. 2006 Dec;244(6):968-76; discussion 976-7.
- 2011-0079