Open, prospective, randomised, multicentre trial on quality assessment of declined liver grafts by normothermic ex situ machine perfusion for decreasing time to transplantation (ExTra trial): a study protocol.

INTRODUCTION

Liver transplantation remains the only curative option for end-stage liver disease, yet high waitlist mortality and organ scarcity continue to challenge the field. The randomised multicentre ExTra trial aims to decrease time-to-transplant by safely improving access to transplantation through viability assessment of otherwise discarded grafts with normothermic machine perfusion (NMP).

METHODS AND ANALYSIS: The ExTra trial is a prospective, randomised, multicentre study conducted across German transplant centres. Participants listed for liver transplantation with a reMELD-Na-Score ≤21 (refitted MELD-Natrium Score) who are not eligible for Standard or Non-Standard Exceptions will be randomised for a 1-year intervention period into two groups: the experimental arm, in which they have-in addition to regular organ allocation-the extra option to receive a graft that was initially deemed non-transplantable based on clinical criteria, but meets specified quality criteria after at least 4 hours of NMP, and the control arm, which consists of conventional allocation procedures alone. The primary endpoint is time-to-transplant, defined as the period between randomisation and transplantation. Secondary outcomes include competing events (death, disease progression or recovery without transplantation), graft and patient survival, quality of life and cost-effectiveness. Additional analyses will assess early graft function, length of hospital stay, biliary complications and 1-year post-transplant outcomes. A centralised biobank will collect perfusate, tissue and blood samples for biomarker research. Safety will be monitored through quarterly reviews by a Data Safety Monitoring Board.

ETHICS AND DISSEMINATION: The study protocol received approval from the Institutional Review Board of the Charité - Universitätsmedizin Berlin on 2 April 2025 (EA1/04/25). Participating study centres will need local Institutional Review Board approval prior to initiation. This study complies with Good Clinical Practice guidelines and all applicable national and local regulations. Results will be disseminated during international and national conference meetings and through publication in a peer-reviewed journal with open access.

TRIAL REGISTRATION NUMBER: NCT06874296.