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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.
• Устройство 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.
• Устройство 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.
• Устройство 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.
• Устройство 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.
• Устройство Normothermic regional perfusion (any device)
  Normothermic regional perfusion followed by static cold storage or any ex situ machine perfusion protocol.
• Другое Static cold storage
  Preservation with static cold storage only, not preceeded by NRP, nor followed by ex situ machine perfusion.

Первичные конечные точки

• Death-censored graft survival [Срок оценки: Actuarial survival 1-5 year post-transplantation]
• Overall patient survival [Срок оценки: Actuarial survival 1-5 year post-transplantation]

Вторичные конечные точки (12)

• Overall graft survival [Срок оценки: Actuarial survival 1-5 year post-transplantation]
• Incidence of major liver-related complications [Срок оценки: within the transplant-related admission, and 1 year post-transplantation]
• Incidence of graft loss due to complications [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Total number of clinically significant biliary complications [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of biliary complications [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of vascular complications [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of re-transplantation [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of acute rejection [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of chronic rejection [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of recurrence of primary disease [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of kidney injury [Срок оценки: within 1 year post-transplantation, up to 5 years post-transplantation]
• Incidence of primary non-function [Срок оценки: up to 1 week post-transplantation]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Великобритания · 2 центра

• King's College Hospital NHS Foundation Trust — London
• Royal Free London NHS Foundation Trust — London

Австрия · 1 центр

• Medical University of Vienna — Vienna

Бельгия · 1 центр

• University Hospitals Leuven — Leuven

Германия · 1 центр

• University Hospital Essen — Essen

Италия · 1 центр

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

Нидерланды · 1 центр

• University Medical Center Groningen — Groningen

Швеция · 1 центр

• Karolinska Institutet — Stockholm

Швейцария · 1 центр

• University Hospital Basel — Basel

Идентификаторы

NCT: NCT07585890 · UMCG_REFRAME-MP · METc 2026/180

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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