Liver Diseases, Liver Transplantation, Surgery
Conditions
Keywords
Liver Transplantation, Extended Criteria Donors, Normothermic Machine Perfusion, Discarded Liver Grafts
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).
Interventions
DEVICEQuality 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.
Sponsors
Charite University, Berlin, Germany
German Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time-to-Transplant | From date of randomization to liver transplantation (up to 12 months after date of randomization) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death | From date of randomization to death (up to 12 months after date of randomization) | Patient death during the 12-month intervention period, regardless of liver transplantation or not. |
| Disease Progression | From date of randomization to event (up to 12 months after date of randomization) | Change of ReMELD-Na-Score above 21 while listed as "transplantable" on the waitlist. Occurence of new contraindication for liver transplantation |
| Proportion of Patients Recovered on the Waitlist | From date of randomization to event (up to 12 months after date of randomization) | 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. |
| Number of patients listed for transplantation after 12 months | 12 months after randomization | Number of patients listed for transplantation after 12 months. |
| Overall patient survival | From date of randomization to death (up to 24 months after date of randomization) | Overall patient survival in the study. |
| Patient-reported Quality of Life | up to 24 months | 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). |
| Graft utilization rate | up to 12 months | Proportion of used livers of all organs offered to patients on the waiting list |
| Inpatient Costs for Liver Transplantation | First 90 days after 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. |
Countries
Germany
Contacts
CONTACTNathanael Raschzok, MD
CONTACTSimon Moosburner, MD
Outcome results
None listed