Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts

NCT ID: NCT01317342

Last Updated: 2021-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 179 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-08-30

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.

Conditions

Hepatocellular Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Hypothermic oxygenated perfusion (HOPE)

Application of HOPE for 1 hour

Group Type: ACTIVE_COMPARATOR

Hypothermic oxygenated perfusion (HOPE)

Intervention Type: DEVICE

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

Control group: no intervention

Conventional cold storage (IGL-1)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philipp Dutkowski

Role: PRINCIPAL_INVESTIGATOR

Department of Surgery and Transplantation, University Hospital Zurich

Locations

University Hospital of Zurich

Zurich, , Switzerland

University of Zurich

Zurich, , Switzerland

Countries

Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 19806056 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18416733 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17122622 (View on PubMed)

Schlegel A, Mueller M, Muller X, Eden J, Panconesi R, von Felten S, Steigmiller K, Sousa Da Silva RX, de Rougemont O, Mabrut JY, Lesurtel M, Cerisuelo MC, Heaton ND, Allard MA, Adam R, Monbaliu D, Jochmans I, Haring MPD, Porte RJ, Parente A, Muiesan P, Kron P, Attia M, Kollmann D, Berlakovich G, Rogiers X, Petterson K, Kranich AL, Amberg S, Mullhaupt B, Clavien PA, Dutkowski P. A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation. J Hepatol. 2023 Apr;78(4):783-793. doi: 10.1016/j.jhep.2022.12.030. Epub 2023 Jan 19.

Reference Type: DERIVED

PMID: 36681160 (View on PubMed)

Other Identifiers

2011-0079

Identifier Type: -

Identifier Source: org_study_id