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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Diseases; Liver Transplantation; Surgery
• Intervention / Treatment: Device: Quality Assessment with Normothermic Machine Perfusion (NMP)

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).

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathanael Raschzok, MD; Phone Number: +49 30 450 552 001; Email: nathanael.raschzok@charite.de
• Study Contact Backup: Name: Simon Moosburner, MD; Phone Number: +49 30 450 552 595; Email: simon.moosburner@charite.de

Study Locations

• Germany
  • Hanover, Germany
    • Recruiting
    • Department of General, Visceral and Transplant Surgery, Hannover Medical School
    • Contact: Philipp Felgendreff, MD; Phone Number: +49 0511 532-6534/6527; Email: felgendreff.philipp@mh-hannover.de
  • München, Germany
    • Recruiting
    • Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich
    • Contact: Michael Eder; Phone Number: +49 089 4400-76573; Email: kcs@med.uni-muenchen.de
  • Regensburg, Germany
    • Recruiting
    • Department of Surgery, University Hospital Regensburg
    • Contact: Stefan Brunner; Phone Number: +49 0941 944-6809; Email: Stefan.Brunner@ukr.de
  • Tübingen, Germany
    • Recruiting
    • Eberhard Karls University of Tübingen, Department of General Visceral and Transplant Surgery
    • Contact: Lisa Vogt; Phone Number: +49 07071 29-61681; Email: Lisa.Vogt@med.uni-tuebingen.de
  • Würzburg, Germany
    • Recruiting
    • Department of General, Visceral, Transplantation, Vascular, and Pediatric Surgery, University Hospital Wurzburg
    • Contact: Johann Lock; Phone Number: +49 931 201-0; Email: Lock_J@ukw.de
  • Free and Hanseatic City of Hamburg
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20251
      • Recruiting
      • University Medical Center Hamburg-Eppendorf
      • Contact: Jacqueline Jahnke-Triankowski; Phone Number: +49 40 7410 52401; Email: j.jahnke-triankowski@uke.de
  • North Rhine-Westphalia
    • Aachen, North Rhine-Westphalia, Germany, 52074
      • Recruiting
      • University Hospital RWTH Aachen
      • Contact: Nils Laurenz; Phone Number: +49 241 80 89500; Email: nlaurenz@ukaachen.de
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Recruiting
      • University Hospital Bonn
      • Contact: Steffen Manekeller, MD; Phone Number: +49 228 287 15215; Email: steffen.manekeller@ukbonn.de
    • Münster, North Rhine-Westphalia, Germany, 49149
      • Recruiting
      • University hospital Muenster
      • Contact: Kerstin Kemmann; Phone Number: +49 251 83 56361; Email: kerstin.kemmann@ukmuenster.de
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Recruiting
      • Department of Surgery Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin
      • Contact: Nathanael Raschzok, MD; Phone Number: +49 30 450 552001; Email: extra-trial@charite.de
      • Principal Investigator: Simon Moosburner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care; Patient will be listed for liver transplantation through standard allocation only.
Experimental: ExTra Option; Patients will receive the option to receive a graft that was declined by all German Transplant Centers but meets predefined quality criteria during at least 4 hours of normothermic machine perfusion (ExTra-LT) or a liver via regular allocation - whichever occurs first. Declined liver grafts will be allocated based on Eurotransplant's first-come-first-serve principle, with consideration for transport logistics and recipient eligibility. Only grafts meeting the following criteria will be considered: Macrovesicular steatosis <60%, fibrosis grade ≤F3, no histopathologic evidence of cirrhosis, graft weight between 1-2.5 kg, no previous machine perfusion preservation.	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, with the exception of biliary viability. These criteria are: Lactate clearance < 2.5 mmol/L, And two or more of the following: Evidence of bile production, maintenance of a perfusate pH >7.30 (without correction for at least one hour), glucose metabolism (falling perfusate glucose value with consistent downward trend), maintenance of stable arterial and portal venous flows (OrganOx Metra: 150 and 500 mL/min respectively), homogeneous perfusion with soft consistency of the parenchyma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-to-Transplant	From date of randomization to liver transplantation (up to 12 months after date of randomization)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Patient death during the 12-month intervention period, regardless of liver transplantation or not.	From date of randomization to death (up to 12 months after date of randomization)
Proportion of Patients Recovered on the Waitlist	Proportion of patients with change in overall health that no liver transplantation is further required in relation to all patients on the waitlist in the trial.	From date of randomization to event (up to 12 months after date of randomization)
Number of patients listed for transplantation after 12 months	Number of patients listed for transplantation after 12 months.	12 months after randomization
Overall patient survival	Overall patient survival in the study.	From date of randomization to death (up to 24 months after date of randomization)
Patient-reported Quality of Life	Patient-reported Quality of Life measured in the EuroQOL EQ5DL. Two aspects will be reported: The EuroQOL visual analog scale (EQ VAS) on a scale from 0-100 points and the proportion of responses by level of severity for the five EQ-5D-5L dimensions (each reported on a five level scale).	up to 24 months
Graft utilization rate	Proportion of used livers of all organs offered to patients on the waiting list	up to 12 months
Inpatient Costs for Liver Transplantation	Analysis of liver transplantation-associated costs. This will be total costs, earnings and profit measured in Euros (EUR) for the primary inpatient stay of liver transplantation.	First 90 days after liver transplantation
Disease Progression	Change of ReMELD-Na-Score above 21 while listed as "transplantable" on the waitlist. Occurence of new contraindication for liver transplantation	From date of randomization to event (up to 12 months after date of randomization)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-month Graft Survival	Graft survival is defined as the need for retransplantation within the first 3 months after liver transplantation. This is one of the "Safety" endpoints and will be evaluated by the Data Safety Monitoring Board.	Within 3 months after date of liver transplantation
3-month Patient Survival	Patient survival is defined as death within the first 3 months after liver transplantation. This is one of the "Safety" endpoints and will be evaluated by the Data Safety Monitoring Board.	Within 3 months after date of liver transplantation
Patient Survival	Patient Survival after liver transplantation	12 months after liver transplantation
Early graft function	Early graft function measured by the Early Allograft Failure Simplified Estimation (EASE) Score on a scale from -6 (extremely low risk) to +6 (unsustainable risk).	Until 10 days after liver transplantation
Intensive Care Unit Stay	Length of stay on the intensive care unit in days.	First 30 days after liver transplantation
Length of Hospital Stay	Total duration of days spent in the hospital after liver transplantation.	First 90 days after liver transplantation
Comprehensive Complication Index	Post-transplant Comprehensive Complication Index, measured on a scale of 0-100, to quantify procedure related morbidity.	Until 90 days after liver transplantation
Biliary Complications	Ischemic-Type Biliary Lesions (clinically and as part of the planned MRCP 12 months after liver transplantation)	Until 12 months after liver transplantation
Graft Survival	Graft survival after liver transplantation.	12 months after liver transplantation
Acceptance Rate	1 / number of unrealized organ offers [accepted for the patient either primarily or within the extended/rescue allocation but not transplanted]	Until 12 months after randomization
Graft-Rescue Rate	Livers that meet quality criteria during NMP / all organs assessed through NMP in the study	Until 12 months after randomization
Risk of Graft Loss	Risk of early graft loss as measured by the Balance of Risk (BAR) Score on a scale from 0-27.	On day of liver transplantation (within the 12 month intervention period after date of randomization)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: German Research Foundation

Publications and helpful links

Helpful Links

• Official Trial Homepage
• Funding Information

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: March 7, 2025
• First Posted (Actual): March 13, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Liver Transplantation; Normothermic Machine Perfusion; Extended Criteria Donors; Discarded Liver Grafts
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 20024292; 543051616 (Other Identifier: German Research Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data will not be shared due to data protection regulations and ethical considerations. Given the sensitive nature of the data, strict confidentiality measures must be maintained to protect participants' privacy. Compliance with GDPR and institutional policies prevents the disclosure of personally identifiable information, ensuring that data handling aligns with legal and ethical standards.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No