Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts

Hepatocellular Injury Clinical Trial

Official title:

A Randomized Multicenter Study on the Effects of Hypothermic Oxygenated Perfusion (HOPE) on Human Liver Grafts Before Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01317342
• Other study ID #: 2011-0079
• Status: Completed
• Phase: N/A
• Start date: April 2015
• Est. completion date: August 30, 2020

Study information

• Verified date: March 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: August 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatocellular Injury
• Hypothermia

Intervention

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

Locations

Country	Name	City	State
Switzerland	University Hospital of Zurich	Zurich
Switzerland	University of Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (3)

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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	major complications after liver transplantation	post transplant complication Clavien >= III within 1 year after transplant	During the first year postoperatively
Secondary	Laboratory parameters post transplant	Serum concentrations of bilirubin, AST, ALT, INR; Factor V	during first week, & 3,6,9,12 months
Secondary	Cholangiopathy	Biliary complications	during 12 months after transplant
Secondary	hospital stay, ICU stay	length of hospital and ICU stay after liver transplantation	during 12 months after transplant
Secondary	Patient and graft survival	one year patient and graft survival	during 12 months after transplant