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

September 4, 2026 updated by: University Medical Center Groningen

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Innsbruck, Austria
        • Not yet recruiting
        • Medical University of Innsbruck
        • Contact:
        • Principal Investigator:
          • Stefan Schneeberger, MD, PhD
      • Vienna, Austria
        • Not yet recruiting
        • Medical University of Vienna
        • Contact:
        • Principal Investigator:
          • Deniz Uluk, MD
  • Belgium
      • Leuven, Belgium
        • Not yet recruiting
        • University Hospitals Leuven
        • Contact:
        • Principal Investigator:
          • Diethard Monbaliu, MD, PhD
  • Germany
      • Essen, Germany
        • Recruiting
        • University Hospital Essen
        • Contact:
        • Principal Investigator:
          • Ulf Neumann, MD, PhD
        • Sub-Investigator:
          • Zoltan Czigany, MD, PhD
  • Italy
      • Torino, Italy
        • Recruiting
        • A.O.U. Città della Salute e della Scienza
        • Contact:
        • Principal Investigator:
          • Damiano Patrono, MD, PhD
  • Netherlands
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen
        • Principal Investigator:
          • Vincent E de Meijer, MD, PhD
        • Contact:
  • Sweden
      • Stockholm, Sweden
        • Not yet recruiting
        • Karolinska Institutet
        • Contact:
        • Principal Investigator:
          • Gabriel Oniscu, MD, PhD
  • Switzerland
      • Bern, Switzerland
        • Not yet recruiting
        • Bern University Hospital
        • Principal Investigator:
          • Philipp Dutkowski, MD, PhD
        • Contact:
  • United Kingdom
      • London, United Kingdom
        • Not yet recruiting
        • Royal Free London NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • David Nasralla, MD, PhD
      • London, United Kingdom
        • Not yet recruiting
        • King's College Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Miriam Cortes Cerisuelo, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All postmortal livers accepted (transplanted and not-transplanted after machine perfusion) upon organ offer between 01.01.2021 and 31.12.2025 for patients >18 years at the time of liver transplantation.

Description

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:

    1. end-ischemic single- or dual hypothermic oxygenated MP [e(D)HOPE],
    2. end-ischemic (back-to-base) normothermic MP [eNMP],
    3. continuous (device-to-donor) normothermic MP [cNMP],
    4. e(D)HOPE followed by controlled oxygenated rewarming and normothermic MP [e(D)HOPE-COR-NMP)],
    5. e(D)HOPE followed by normothermic MP [e(D)HOPE-NMP], or
    6. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Actuarial survival 1-5 year post-transplantation
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).
Actuarial survival 1-5 year post-transplantation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Actuarial survival 1-5 year post-transplantation
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.
within the transplant-related admission, and 1 year post-transplantation
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.
within 1 year post-transplantation, up to 5 years post-transplantation
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).
within 1 year post-transplantation, up to 5 years post-transplantation
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
within 1 year post-transplantation, up to 5 years post-transplantation
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
within 1 year post-transplantation, up to 5 years post-transplantation
Incidence of re-transplantation
Time Frame: within 1 year post-transplantation, up to 5 years post-transplantation
Re-transplantation for any cause.
within 1 year post-transplantation, up to 5 years post-transplantation
Incidence of acute rejection
Time Frame: within 1 year post-transplantation, up to 5 years post-transplantation
within 1 year post-transplantation, up to 5 years post-transplantation
Incidence of chronic rejection
Time Frame: within 1 year post-transplantation, up to 5 years post-transplantation
within 1 year post-transplantation, up to 5 years post-transplantation
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
within 1 year post-transplantation, up to 5 years post-transplantation
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
within 1 year post-transplantation, up to 5 years post-transplantation
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
up to 1 week post-transplantation
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)
within 1 year post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Medical Center Groningen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
A.O.U. Città della Salute e della Scienza

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vincent E de Meijer, MD, PhD, University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 21, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 21, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UMCG_REFRAME-MP
  • METc 2026/180 (Registry Identifier: UMCG METc number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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