NCT01317342

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
179

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 10, 2011

Completed
7 days until next milestone

First Posted

Study publicly available on registry

March 17, 2011

Completed
4 years until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 30, 2020

Completed
Last Updated

March 25, 2021

Status Verified

March 1, 2021

Enrollment Period

5.4 years

First QC Date

March 10, 2011

Last Update Submit

March 22, 2021

Conditions

Hepatocellular Injury

Keywords

liver transplantationmachine liver perfusionextended criteria liver graftsdonation after cardiac deathhypothermic machine liver perfusionliver reperfusion injury

Outcome Measures

Primary Outcomes (1)

  • major complications after liver transplantation

    post transplant complication Clavien \>= III within 1 year after transplant

    During the first year postoperatively

Secondary Outcomes (4)

  • Laboratory parameters post transplant

    during first week, & 3,6,9,12 months

  • Cholangiopathy

    during 12 months after transplant

  • hospital stay, ICU stay

    during 12 months after transplant

  • Patient and graft survival

    during 12 months after transplant

Study Arms (2)

Hypothermic oxygenated perfusion (HOPE)

ACTIVE COMPARATOR

Application of HOPE for 1 hour

Device: Hypothermic oxygenated perfusion (HOPE)

Control group: no intervention

NO INTERVENTION

Conventional cold storage (IGL-1)

Interventions

Hypothermic oxygenated perfusion (HOPE)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

Hypothermic oxygenated perfusion (HOPE)

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University Hospital of Zurich

Zurich, 8091, Switzerland

Location

University of Zurich

Zurich, 8091, Switzerland

Location

Related Publications (4)

  • 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.

    PMID: 19806056BACKGROUND

  • 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.

    PMID: 18416733BACKGROUND

  • 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.

    PMID: 17122622BACKGROUND

  • 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.

    PMID: 36681160DERIVED

Study Officials

  • Philipp Dutkowski

    Department of Surgery and Transplantation, University Hospital Zurich

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 10, 2011

First Posted

March 17, 2011

Study Start

April 1, 2015

Primary Completion

August 30, 2020

Study Completion

August 30, 2020

Last Updated

March 25, 2021

Record last verified: 2021-03

Locations

CH(2)