Assessing Declined Liver Grafts With Normothermic Machine Perfusion to Reduce Transplant Waiting Time

Official title

Pilot, Open, Prospective, Randomized, Multicenter Trial On Quality Assessment Of Declined Liver Grafts By Normothermic Ex Vivo Machine Perfusion For Decreasing Time To Transplantation

Overview

The goal of this study is to find out if quality assessment by normothermic machine perfusion can be used to safely increase the number of usable donor livers, helping more people get transplants faster and with better results. This process keeps a donated liver working outside the body before transplantation, allowing surgeons to assess whether livers previously considered unsuitable can still be used. The main questions this study aims to answer are: * Does this method help patients get a transplant sooner? * Can this method make more livers available for transplant? * Does it improve survival and health after transplant? Participants in this study must be on the waiting list for a liver transplant with a ReMELD-Na-Score of 21 or less (equivalent to MELD ≤25) and must not qualify for certain special exceptions. Participants will be randomly placed into one of two groups: * Experimental group: In addition to regular organ offers, these participants may receive a liver that was initially not considered for transplantation but meets quality standards after at least four hours of machine perfusion. * Control group: These participants will receive a liver through the usual transplant process. The main measure of success is how quickly participants receive a transplant. Researchers will also look at other important factors, such as survival rates, quality of life, hospital stay, and complications after transplant. This study may help improve liver transplantation by making better use of available donor livers, reducing waiting times, and improving patient outcomes.

Detailed description

Liver transplantation is the treatment of choice for patients with advanced liver cirrhosis, hepatocellular carcinoma within the Milan criteria, and severe metabolic or autoimmune liver diseases. However, organ shortage remains a significant issue, particularly in Germany, where only 58% of patients on the waiting list received a transplant in 2022. Patients with MELD ≤25, who are ineligible for \[Non\]-Standard Exception criteria, face particularly long waiting times and lower transplant rates.

Despite the shortage, approximately 24% of all liver grafts in Germany are declined due to donor age, macrosteatosis, or prolonged cold ischemia. Emerging technologies, such as NMP, allow for objective graft quality assessment before transplantation. Several non-randomized studies in the UK, Netherlands, Australia, and the USA have demonstrated the potential of NMP to increase organ utilization. The ExTra trial is the first randomized controlled study to investigate whether declined liver grafts, following NMP-based quality assessment, can safely and effectively reduce the waiting time for patients with ReMELD-Na-Score ≤ 21(equivalent to MELD ≤25).

Interventions

• Device Quality Assessment with Normothermic Machine Perfusion (NMP)
  Quality assessment using NMP in the experimental arm is performed according to previously published viability criteria for initially declined liver grafts, which are mandatory for all participating study centers, with minor device-specific modifications. These criteria are based on the Birmingham criteria used in the VITTAL trial for viability assessment of DBD and DCD grafts with the OrganOx Metra device and are comparable to the Groningen criteria used with the LiverAssist and PerLife device,

Primary outcome measures

• Time-to-Transplant [Time frame: From date of randomization to liver transplantation (up to 12 months after date of randomization)]

Secondary outcome measures (8)

• Death [Time frame: From date of randomization to death (up to 12 months after date of randomization)]
• Disease Progression [Time frame: From date of randomization to event (up to 12 months after date of randomization)]
• Proportion of Patients Recovered on the Waitlist [Time frame: From date of randomization to event (up to 12 months after date of randomization)]
• Number of patients listed for transplantation after 12 months [Time frame: 12 months after randomization]
• Overall patient survival [Time frame: From date of randomization to death (up to 24 months after date of randomization)]
• Patient-reported Quality of Life [Time frame: up to 24 months]
• Graft utilization rate [Time frame: up to 12 months]
• Inpatient Costs for Liver Transplantation [Time frame: First 90 days after liver transplantation]

Eligibility criteria

Inclusion criteria

• Able to consent
• ≥ 18 years old
• Listed in status "transplantable" by the transplant conference of the study centre for liver transplantation, according to the guidelines of the German Medical Association valid at the time of inclusion
• ReMELD-Na-Score ≤ 21 (equivalent to MELD ≤25), not eligible for \[non\]standard exceptions
• Medically suitable and informed for transplantation with an organ that fulfils extended donor criteria (Eurotransplant ECD criteria)
• Patient information and written consent to participate in the Extra trial
• No participation in another interventional study during participation

Exclusion criteria

• Listed for retransplantation
• High-Urgency Listing
• Listed for combined organ transplantation
• Pregnancy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 10 centers

• University Medical Center Hamburg-Eppendorf — Hamburg
• University Hospital RWTH Aachen — Aachen
• University Hospital Bonn — Bonn
• University Hospital Muenster — Münster
• Department of Surgery Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitä — Berlin
• Department of General, Visceral and Transplant Surgery, Hannover Medical School — Hanover
• Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU — München
• Department of Surgery, University Hospital Regensburg — Regensburg
• … and 2 more centers

Identifiers

NCT: NCT06874296 · 20024292 · 543051616

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗