Hypothermic Oxygenated Perfusion for Extended Criteria Donors in Liver Transplantation (HOPExt)

NCT03929523 | Completed DMC

• 2 other identifiers: 69HCL19_00342019-A00546-51
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 8

Brief Summary

Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs have been used for liver transplantation. These ECD liver grafts are, however, known to be associated with a higher rate of early allograft dysfunction (EAD) and primary non-function because of a greater vulnerability to ischemia-reperfusion injury. The end-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. The study aim is to assess the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative EAD within the first 7 postoperative days (POD) compared to simple cold static storage. The study is comparative open-label, multicenter, national, prospective, randomized, in two parallel groups, using the gold standard procedure as control.

Conditions

Liver Transplantation

Keywords

Liver Transplantation; Liver machine perfusion; extended criteria donor

Outcome Measures

Primary Outcomes (1)

• Early allograft dysfunction (EAD) according to Olthoff criteria.

  EAD is defined by the presence of at least one of the following criteria: * Bilirubin level \> 10 mg/dL (i.e. 171 µmol/L) on POD 7 * International Normalized Ratio (INR) \> 1.6 on POD 7 * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels \> 2000 IU/L within the first 7 PODs Additionally EAD will be also assessed by the MEAF score and the L-GrAFT risk factor.

  During the first postoperative week

Secondary Outcomes (10)

• Model of Early Allograft Function score (MEAF score).

  During the first 3 postoperative days.

• Liver Graft Assessment Following Transplantation risk factor (L-GrAFT)

  During the first 10 postoperative days.

• Untargeted liver graft metabolic profiling

  Day of liver transplantation (Day 0)

• Occurrence of post-reperfusion syndrome

  Day of liver transplantation (Day 0)

• 90-day morbidity and mortality

  During the first 90 days after surgery.

Study Arms (2)

HOPE group

EXPERIMENTAL

hypothermic oxygenated perfusion

Device: End-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE)

Control group

ACTIVE COMPARATOR

classic static cold storage

Device: classic static cold storage

Interventions

End-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) DEVICE

In the experimental group, ECD liver grafts will first undergo a classical static cold (4°C) storage with Institute George Lopez (IGL-1)® solution from graft harvesting until transport to the transplantation center. They will then undergo a hypothermic oxygenated perfusion (HOPE) via the portal vein for a period of 1 to 4 hours (minimum 1 hour) after the "back-table" phase (graft preparation), in parallel with the recipient hepatectomy, using the CE-certified Liver Assist® perfusion pump/device (Organ Assist®, the Netherlands) with Machine Perfusion Solution (Belzer-MPS, CE-certified).

HOPE group

classic static cold storage DEVICE

The control group will consist of a classic static cold (4°C) storage with Institute George Lopez (IGL-1)® solution from graft harvesting until liver transplantation, which is the gold standard procedure in liver transplantation

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent prior to the performance of any study specific procedure
• Affiliated to the French social security system
• Recipient age ≥ 18 years
• Patients undergoing primary liver transplantation.
• Candidate for a first elective liver transplantation, whatever the indication, with a liver graft harvested from a brain-dead ECD defined by the presence of at least one of the following criteria:
• Donor age \> 65 years
• Intensive care unit stay \> 7 days
• BMI \> 30
• Proven macro-steatosis biopsy ≥ 30%
• Natremia \> 155 mmol/L at any time
• AST \> 150 IU/mL at any time
• ALT \> 170 IU/mL at any time.

You may not qualify if:

• Fulminant hepatic failure
• Retransplantation
• Split liver transplantation
• Living donor liver transplantation
• Grafts donated after cardiac arrest (DCD grafts)
• Domino transplantation
• Combined liver transplant
• Unexpected medical contraindication to liver transplantation
• Patient participating in other interventional research, excluding routine care research (old regulation) and category 2 research not interfering with primary endpoint analysis
• Patient under legal protection
• Patient deprived of liberty by a judicial or administrative decision
• Patient refusing to participate in the study
• Pregnant or lactating women
• Inability to understand information concerning the protocol

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (8)

Department of HPB surgery and liver transplantation Beaujon University Hospital

Clichy, 92210, France

Location

CHU Grenoble Alpes - Department of HPB surgery and liver transplantation

Grenoble, 38000, France

Location

Department of HPB surgery and liver transplantation Claude Huriez University Hospital

Lille, 59037, France

Location

Hospices Civils de Lyon

Lyon, 69004, France

Location

APHP - Pitié Salpétrière

Paris, 75013, France

Location

Department of HPB surgery and liver transplantation Pontchaillou University Hospital

Rennes, 35033, France

Location

Hôpital Hautepierre - Department of HPB surgery and liver transplantation

Strasbourg, 67200, France

Location

Department of HPB surgery and liver transplantation Paul Brousse University Hospital

Villejuif, 94804, France

Location

Related Publications (2)

• Pradat P, Pantel S, Maynard M, Lalande L, Thevenon S, Adam R, Allard MA, Robin F, Rayar M, Boleslawski E, Scatton O, Chirica M, Faitot F, Bachellier P, Soubrane O, Mohkam K, Mabrut JY, Lesurtel M. End-ischemic hypothermic oxygenated perfusion for extended criteria donors in liver transplantation: a multicenter, randomized controlled trial-HOPExt. Trials. 2023 Jun 6;24(1):379. doi: 10.1186/s13063-023-07402-0.

  PMID: 37280696 BACKGROUND

• Lesurtel M, Mohkam K, Allard MA, Adam R, Robin F, Rayar M, Boudjema K, Chebaro A, Boleslawski E, Savier E, Scatton O, Girard E, Chirica M, Dokmak S, Soubrane O, Faitot F, Bachellier P, Hervieu V, Guerre P, Atfeh J, Pantel S, Thevenon S, Maynard M, Pradat P, Mabrut JY. A French multicenter randomized controlled trial of hypothermic oxygenated perfusion in extended criteria donor liver transplantation. Am J Transplant. 2025 Oct 17:S1600-6135(25)03053-9. doi: 10.1016/j.ajt.2025.10.006. Online ahead of print.

  PMID: 41110608 RESULT

Study Officials

• Mickael LESURTEL

  APHP Beaujon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 29, 2019
• Study Start: September 10, 2019
• Primary Completion: March 13, 2023
• Study Completion: March 13, 2023
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)