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NCT Number: NCT03929523

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

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.

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Key information

Conditions

Liver Transplantation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of HPB surgery and liver transplantation Beaujon University Hospital, Clichy, France

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About this study

This multicentric randomized controlled trial concerns adult patients undergoing whole liver transplantation in any of the 8 participating centers in France, who will receive an ECD liver graft from a brain-dead donor.

After providing written informed consent prior to the performance of any study specific procedure, the recruited patients will be randomized either in the experimental group (HOPE group) or in the control group.

In the HOPE group, ECD liver grafts will 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).

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.

The primary endpoint will be early allograft dysfunction (EAD) according to Olthoff's criteria, which will be compared with the Model of Early Allograft Function score (MEAF score) and the Liver Graft Assessment Following Transplantation risk factor (L-GrAFT).

According to the primary endpoint, a sample size of 133 patients per randomized group (266 in total) is needed. The duration of the inclusion period is expected to be 36 months with a 1-year follow-up for each patient.

The potential impacts of the study are expected on 3 levels: (1) for the patient, decreased postoperative morbidity and mortality of liver transplantation with ECD donors; (2) for the French liver transplantation community, familiarization with liver machine perfusion, and (3) economically, decreased costs of liver transplantation (health economic analysis included in the study).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

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).

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

Primary outcomes

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

    Time frame: During the first postoperative week

    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.

Secondary outcomes

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

    Time frame: During the first 3 postoperative days.

    The MEAF score includes bilirubin, ALT max and INR max at postperative day 3. Range 0 (better outcome) to 10 (worse outcome)

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

    Time frame: During the first 10 postoperative days.

    L-GrAFT includes aspartate aminotransferase (AST), INR, total bilirubin and platelets every day until postoperative day 10. Range -6 (better outcome) to +6 (worse outcome)

  3. Untargeted liver graft metabolic profiling

    Time frame: Day of liver transplantation (Day 0)

    Untargeted liver graft metabolic profiling (by High-Resolution Nuclear Magnetic Resonance - 1H HR-Nuclear Magnetic Resonance (NMR) Spectrometer) on liver graft biopsies on the back-table before and after liver machine perfusion.

  4. Occurrence of post-reperfusion syndrome

    Time frame: Day of liver transplantation (Day 0)

    Defined as a 50% decrease in median arterial pressure during the 5 minutes following the graft revascularization

  5. 90-day morbidity and mortality

    Time frame: During the first 90 days after surgery.

    Severe postoperative complications (Dindo-Clavien ≥3) / death

  6. Length of intermediate care unit stay (days)

    Time frame: From randomization until intermediate care unit discharge, estimated up to 7 days

    Duration of intermediate care unit stay

  7. Length of hospital stay (days)

    Time frame: From randomization until hospital discharge, estimated up to 21 days

    Duration of hospital stay

  8. Liver contrast-enhanced MRI including a Magnetic Resonance CholangioPancreatography (MRCP)

    Time frame: Within 1 year after liver transplantation

    Assessment of intra- and extrahepatic biliary complications (except for patients who underwent a re-transplanted during the study).

  9. 3-month and one-year patient and graft survivals

    Time frame: within one year after liver transplantation

    Actuarial graft and patient's survival rates

  10. Hospital costs (Euros) of liver transplantation

    Time frame: At one year after liver transplantation

    Hospital costs of liver transplantation

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

End-ischemic Hypothermic Oxygenated Perfusion for Extended Criteria Donors in Liver Transplantation - A Multicenter, Randomized Controlled Trial

Acronym: HOPExt

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Apr 29, 2019
Registry last updated
Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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