DFG Funding for the ExTra trial to Reduce Time-to-Transplant for Liver Transplantation

Prof. Dr. med. Nathanael Raschzok, Fellow of the BIH Charité Advanced Clinician Scientist Program and alumnus of the Clinician Scientist Program, and his team at the Department of Surgery, Charité Campus Mitte | Campus Virchow-Klinikum, have received funding from the German Research Foundation (DFG) to conduct a clinical trial aimed at reducing time-to-transplant for liver transplantation. The ExTra Study (Pilot, open, prospective, randomized, multicenter trial on quality assessment of declined liver grafts by normothermic Ex vivo machine perfusion for decreasing time to Transplantation) is supported by a grant of 1.85 million euros, with the goal of shortening the wait time for liver transplants by assessing the quality of declined liver grafts using ex vivo machine perfusion.

In Germany, there is a critical shortage of donor organs, and the liver transplant waiting list is marked by a high mortality rate. Each year, a substantial number of organs are not transplanted due to quality concerns. However, pilot studies indicate that declined liver grafts can be successfully transplanted following quality assessment using normothermic ex vivo machine perfusion.

The ExTra Study will be conducted in collaboration with the German Organ Transplantation Foundation, Eurotransplant, all German liver transplant centers, and an internationally staffed advisory board. The focus is on shortening the waiting time for patients with a MELD score ≤25 who do not qualify for exception points. The study plans to enroll 83 patients in each arm: “Standard Therapy” and the experimental arm with the “ExTra Option.” In the experimental arm, patients will be offered the opportunity to receive a graft that was declined in the standard allocation process due to quality concerns. These organs will undergo stringent quality checks and, following machine perfusion, be deemed suitable for transplantation.

Primary and Secondary Endpoints of the Study

The primary endpoint is “time to transplant,” assessing whether the ExTra Option — i.e. utilizing initially declined grafts deemed suitable for transplantation by normothermic machine perfusion — can reduce transplant waiting times for patients with a MELD score ≤25, compared to standard therapy. Secondary endpoints include the procedure’s safety, graft utilization, and associated costs. In the experimental arm, the ExTra Option will be available in addition to the standard allocation process. The grafts will be evaluated on perfusion systems using blood gas analyses and perfusion parameters, with post-transplant outcomes monitored based on clinical and paraclinical parameters.

Potential for Clinical Implementation

Should the study succeed, assessing the quality of organs initially deemed non-transplantable through normothermic machine perfusion could become a clinical standard in Germany. This would be a significant step toward expanding the donor pool for liver transplants, improving transplant opportunities for all patients on the waiting list. Some risk of post-transplant complications remains; thus, strict quality criteria based on the VITTAL Trial from Birmingham and a pilot study from Groningen have been defined. To mitigate risks and ensure rapid response when needed, an international DSMB (Prof. Selzner/Toronto, Prof. Patel/Dallas, Prof. Wenden/London, and Prof. Roderburg/Düsseldorf) has been established. Additionally, the study protocol is reviewed by Prof. de Meijer (Groningen) and Dr. Mergentahl (Birmingham), who conducted the key pilot studies.

Study Timeline

The ethics application is currently being submitted, and study initiation and first patient enrollment are planned for the second quarter of 2025.