Clinical trial NCT06874296: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Liver Transplantation
Liver Diseases
Surgery
Keywords: Liver Transplantation
Extended Criteria Donors
Normothermic Machine Perfusion
Discarded Liver Grafts
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2025-03-13
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The treatment in the intervention arm will be available for patient for 12 months after randomization. Patients who have not yet received a graft after 12 months and are therefore still on the waiting list are administratively censored.
Primary purpose: TREATMENT

Brief summary: 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).

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

Primary outcomes:
measure: Time-to-Transplant
timeFrame: From date of randomization to liver transplantation (up to 12 months after date of randomization)
Secondary outcomes:
measure: Death
timeFrame: From date of randomization to death (up to 12 months after date of randomization)
measure: Disease Progression
timeFrame: From date of randomization to event (up to 12 months after date of randomization)
measure: Proportion of Patients Recovered on the Waitlist
timeFrame: From date of randomization to event (up to 12 months after date of randomization)
measure: Number of patients listed for transplantation after 12 months
timeFrame: 12 months after randomization
measure: Overall patient survival
timeFrame: From date of randomization to death (up to 24 months after date of randomization)
measure: Patient-reported Quality of Life
timeFrame: up to 24 months
measure: Graft utilization rate
timeFrame: up to 12 months
measure: Inpatient Costs for Liver Transplantation
timeFrame: First 90 days after liver transplantation
Other outcomes:
measure: 3-month Graft Survival
timeFrame: Within 3 months after date of liver transplantation
measure: 3-month Patient Survival
timeFrame: Within 3 months after date of liver transplantation
measure: Patient Survival
timeFrame: 12 months after liver transplantation
measure: Early graft function
timeFrame: Until 10 days after liver transplantation
measure: Intensive Care Unit Stay
timeFrame: First 30 days after liver transplantation
measure: Length of Hospital Stay
timeFrame: First 90 days after liver transplantation
measure: Comprehensive Complication Index
timeFrame: Until 90 days after liver transplantation
measure: Biliary Complications
timeFrame: Until 12 months after liver transplantation
measure: Graft Survival
timeFrame: 12 months after liver transplantation
measure: Acceptance Rate
timeFrame: Until 12 months after randomization
measure: Graft-Rescue Rate
timeFrame: Until 12 months after randomization
measure: Risk of Graft Loss
timeFrame: On day of liver transplantation (within the 12 month intervention period after date of randomization)
Locations:
city: Berlin
country: Germany
facility: Department of Surgery Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin
Study officials:
References: