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NCT Number: NCT07585890

Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe

Machine perfusion (MP) has become routine clinical practice in liver transplantation. However, as the field has matured, direct randomized comparisons between distinct MP modalities have become increasingly impractical, given that donor and graft characteristics often predetermine the optimal preservation strategy. Consequently, many studies continue to reference historical benchmark cohorts from the pre-perfusion era, or use risk scores developed before routine utilization of MP. These cohorts, while once valuable, fail to account for the paradigm shift that MP has introduced. Likewise, commonly used donor- and recipient-based risk scores were developed prior to the adoption of MP. While these scores aim to assess survival or morbidity after transplantation, none of them guide decisions about MP use or the most suitable perfusion protocol. As MP technologies continue to evolve there is a critical need for an updated reference framework that accurately reflects current clinical practice and captures the best achievable outcomes across all MP modalities.

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Key information

Conditions

End-stage Liver Disease (ESLD) Acute Liver Failure Digestive System Diseases End Stage Liver Disease Fibrosis Hepatic Insufficiency Liver Cirrhosis Liver Diseases Liver Failure Liver Failure, Acute Liver Transplantation Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

A.O.U. Città della Salute e della Scienza, Torino, Italy

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About this study

The aim of this study is to establish a reference framework for liver transplantation outcomes in the era of routine clinical machine perfusion. In addition, based on the collected real-world observational data, a target trial emulation approach will be applied.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • All postmortal livers accepted (transplanted and not-transplanted after machine perfusion) upon organ offer for patients >18 years at the time of liver transplantation.
  • All donor types (DBD, DCD)
  • Preservation either with static cold storage alone or combined with machine perfusion (MP).
  • Donor livers underwent MP as part of routine clinical practice and the choice of perfusion protocol was made according to institutional standard practice.
  • Eligible MP protocols are:
  • end-ischemic single- or dual hypothermic oxygenated MP [e(D)HOPE],
  • end-ischemic (back-to-base) normothermic MP [eNMP],
  • continuous (device-to-donor) normothermic MP [cNMP],
  • e(D)HOPE followed by controlled oxygenated rewarming and normothermic MP [e(D)HOPE-COR-NMP)],
  • e(D)HOPE followed by normothermic MP [e(D)HOPE-NMP], or
  • Normothermic regional perfusion followed by SCS or an ex situ MP protocol.
  • A minimum follow-up of 12 months after liver transplantation is required.

Exclusion criteria

  • Livers that were allocated to a MP protocol as part of a prospective randomized or interventional clinical trial comparing different preservation techniques or any other invention.
  • Living donor liver transplantation

Treatment and study plan

Endischemic hypothermic oxygenated machine perfusion (any device)

Device

Endischemic single- or dual hypothermic oxygenated machine perfusion. Normothermic regional perfusion prior to single- or dual hypothermic oxygenated machine perfusion is eligible for inclusion.

Endischemic (back-to-base) normothermic machine perfusion (any device)

Device

Endischemic (back-to-base) normothermic machine perfusion. Normothermic regional perfusion prior to endischemic (back-to-base) normothermic machine perfusion is eligible for inclusion.

Continuous (device-to-donor) normothermic machine perfusion (any device)

Device

Continuous (device-to-donor) normothermic machine perfusion. Normothermic regional perfusion prior to continuous (device-to-donor) normothermic machine perfusion is eligible for inclusion.

Endischemic HOPE-COR-NMP (any device)

Device

Endischemic single or dual hypothermic oxygenated machine perfusion followed by controlled oxygenated rewarming and normothermic machine perfusion.

Normothermic regional perfusion prior to HOPE-COR-NMP is eligible for inclusion.

Endischemic HOPE-NMP (any device)

Device

Endischemic single or dual hypothermic oxygenated machine perfusion followed by normothermic machine perfusion.

Normothermic regional perfusion prior to HOPE-NMP is eligible for inclusion.

Normothermic regional perfusion (any device)

Device

Normothermic regional perfusion followed by static cold storage or any ex situ machine perfusion protocol.

Static cold storage

Other

Preservation with static cold storage only, not preceeded by NRP, nor followed by ex situ machine perfusion.

Primary outcomes

  1. Death-censored graft survival

    Time frame: Actuarial survival 1-5 year post-transplantation

    Defined as the time from liver transplantation until re-transplantation or death due to graft failure (analyzed using time-to-event methods).

  2. Overall patient survival

    Time frame: Actuarial survival 1-5 year post-transplantation

    Defined as time from liver transplantation until re-transplantation or all-cause death (analyzed using time-to-event methods).

Secondary outcomes

  1. Overall graft survival

    Time frame: Actuarial survival 1-5 year post-transplantation

    Defined as time from liver transplantation until re-transplantation or all-cause death (analyzed using time-to-event methods)

  2. Incidence of major liver-related complications

    Time frame: within the transplant-related admission, and 1 year post-transplantation

    Incidence of at least one biliary or vascular complication graded as Clavien-Dindo IIIb or higher, following the grading recommendations published: de Goeij FHC, Wehrle CJ, Abbassi F, et al. Mastering the narrative: Precision reporting of risk and outcomes in liver transplantation. J Hepatol. 2025;82(4):729-743. doi:10.1016/j.jhep.2024.11.013. Additionally, scoring accoring the Comprehensive Complication Index.

  3. Incidence of graft loss due to complications

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Graft loss as a result of complications assessed separately for biliary complications, vascular complications, and rejection.

  4. Total number of clinically significant biliary complications

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Total number of any biliary complications requiring interventions (Clavien-Dindo grade IIIa or higher).

  5. Incidence of biliary complications

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Biliary complications include:

    • Post-transplant cholangiopathy
    • Anastomotic strictures
    • Biliary leakage

  6. Incidence of vascular complications

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Vascular complications include:

    • Hepatic artery thrombosis
    • Portal vein thrombosis
    • Venous outflow tract obstruction

  7. Incidence of re-transplantation

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Re-transplantation for any cause.

  8. Incidence of acute rejection

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

  9. Incidence of chronic rejection

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

  10. Incidence of recurrence of primary disease

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Histologically or radiologically confirmed recurrence, including recurrence of malignancies

  11. Incidence of kidney injury

    Time frame: within 1 year post-transplantation, up to 5 years post-transplantation

    Kidney injury includes:

    • Acute kidney injury
    • New-onset chronic kidney disease

  12. Incidence of primary non-function

    Time frame: up to 1 week post-transplantation

    Liver graft failure within the first 7 days of transplantation with patent liver vessels leading to re-transplantation or patient death

  13. Patient-centered outcomes (measure of recovery and healthcare utilization)

    Time frame: within 1 year post-transplantation

    Length of intensive care unit stay and length of initial hospital stay (starting at day of transplantation until day of discharge, measured in days)

Study contacts

Contact information is provided by the study sponsor or research team.

Sabrina Stimmeder, MD

CONTACT

[email protected]

‭+31503612896‬

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Collaborators

  • A.O.U. Città della Salute e della Scienza

Registry information

Official study title

Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe (REFRAME-MP)

Acronym: REFRAME-MP

Important dates

Study start
2026
Primary completion
2026
Study completion
2030
First posted
May 14, 2026
Registry last updated
May 14, 2026

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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