Clinical trial NCT01317342: Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts
Official title: A Randomized Multicenter Study on the Effects of Hypothermic Oxygenated Perfusion (HOPE) on Human Liver Grafts Before Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatocellular Injury
Keywords: liver transplantation
machine liver perfusion
extended criteria liver grafts
donation after cardiac death
hypothermic machine liver perfusion
liver reperfusion injury
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2011-03-17
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: major complications after liver transplantation
timeFrame: During the first year postoperatively
Secondary outcomes:
measure: Laboratory parameters post transplant
timeFrame: during first week, & 3,6,9,12 months
measure: Cholangiopathy
timeFrame: during 12 months after transplant
measure: hospital stay, ICU stay
timeFrame: during 12 months after transplant
measure: Patient and graft survival
timeFrame: during 12 months after transplant
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital of Zurich
city: Zurich
country: Switzerland
facility: University of Zurich
Study officials:
affiliation: Department of Surgery and Transplantation, University Hospital Zurich
name: Philipp Dutkowski
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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. doi: 10.1097/01.sla.0000247056.85590.6b.