Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Endischemic hypothermic oxygenated machine perfusion (any device), Endischemic (back-to-base) normothermic machine perfusion (any device), Continuous (device-to-donor) normothermic machine perfusion (any device), Endischemic HOPE-COR-NMP (any device).
- Who it may be relevant to
- Registry conditions: End-stage Liver Disease (ESLD), Acute Liver Failure, Liver Cirrhosis, Liver Transplantation. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Austria, Belgium, Germany, Italy, Netherlands +3
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe (REFRAME-MP)
Overview
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.
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.
Interventions
- Device Endischemic hypothermic oxygenated machine perfusion (any 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. - Device Endischemic (back-to-base) normothermic machine perfusion (any device)
Endischemic (back-to-base) normothermic machine perfusion. Normothermic regional perfusion prior to endischemic (back-to-base) normothermic machine perfusion is eligible for inclusion. - Device Continuous (device-to-donor) normothermic machine perfusion (any device)
Continuous (device-to-donor) normothermic machine perfusion. Normothermic regional perfusion prior to continuous (device-to-donor) normothermic machine perfusion is eligible for inclusion. - Device Endischemic HOPE-COR-NMP (any 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. - Device Endischemic HOPE-NMP (any 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. - Device Normothermic regional perfusion (any device)
Normothermic regional perfusion followed by static cold storage or any ex situ machine perfusion protocol. - Other Static cold storage
Preservation with static cold storage only, not preceeded by NRP, nor followed by ex situ machine perfusion.
Primary outcome measures
- Death-censored graft survival [Time frame: Actuarial survival 1-5 year post-transplantation]
- Overall patient survival [Time frame: Actuarial survival 1-5 year post-transplantation]
Secondary outcome measures (12)
- Overall graft survival [Time frame: 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 graft loss due to complications [Time frame: 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]
- Incidence of biliary complications [Time frame: 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]
- Incidence of re-transplantation [Time frame: 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]
- Incidence of chronic rejection [Time frame: 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]
- Incidence of kidney injury [Time frame: within 1 year post-transplantation, up to 5 years post-transplantation]
- Incidence of primary non-function [Time frame: up to 1 week post-transplantation]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United Kingdom · 2 centers
- King's College Hospital NHS Foundation Trust — London
- Royal Free London NHS Foundation Trust — London
Austria · 1 center
- Medical University of Vienna — Vienna
Belgium · 1 center
- University Hospitals Leuven — Leuven
Germany · 1 center
- University Hospital Essen — Essen
Italy · 1 center
- A.O.U. Città della Salute e della Scienza — Torino
Netherlands · 1 center
- University Medical Center Groningen — Groningen
Sweden · 1 center
- Karolinska Institutet — Stockholm
Switzerland · 1 center
- University Hospital Basel — Basel
Identifiers
NCT: NCT07585890 · UMCG_REFRAME-MP · METc 2026/180