Early Allograft Dysfunction, Ischemia-Reperfusion Injury, Liver Transplantation (LT)
Conditions
Keywords
Liver Transplantation, Normothermic Machine Perfusion, Ischemia-Reperfusion Injury, Early Allograft Dysfunction, Organ Preservation, Liver Graft
Brief summary
The ARANMP-LT study is a multicenter, open-label, randomized, parallel-group, non-inferiority clinical trial designed to evaluate whether avoiding graft recooling after normothermic machine perfusion (NMP) improves early outcomes following liver transplantation. Although graft recooling before implantation is common practice, experimental and preliminary clinical evidence suggests that abrupt temperature changes may contribute to ischemia-reperfusion injury. Adult recipients of deceased-donor liver grafts preserved with NMP or sequential hypothermic-normothermic machine perfusion (SHNMP) will be randomized in a 1:1 ratio to either standard graft implantation with recooling using cold preservation solution (control group) or implantation without recooling using a room-temperature 5% albumin flush immediately before reperfusion (intervention group). The primary objective is to compare the incidence of Early Allograft Dysfunction (EAD), defined according to the Olthoff criteria, between the two treatment groups. Secondary objectives include evaluation of histopathological ischemia-reperfusion injury using the Suzuki score, vascular and biliary complications, primary non-function, post-reperfusion syndrome, patient and graft survival, length of intensive care unit and hospital stay, perioperative transfusion requirements, and safety outcomes. A total of 170 participants will be enrolled across multiple Italian liver transplant centers and followed for 90 days after transplantation.
Interventions
PROCEDURENo Recooling Before Liver Implantation
After completion of normothermic machine perfusion, the liver graft is flushed with 5% albumin solution at room temperature (20-25°C) and implanted without recooling. The graft remains at near-normothermic temperature throughout the transition from ex vivo perfusion to in situ implantation, avoiding the conventional cold preservation flush before reperfusion.
PROCEDURETraditional Recooling Before Liver Implantation
After completion of normothermic machine perfusion, the liver graft undergoes the standard preservation procedure consisting of a cold preservation solution flush before implantation, resulting in graft recooling prior to reperfusion. The remainder of the transplantation procedure follows standard clinical practice.
Sponsors
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Listed for primary liver transplantation at the participating institution. * Assigned a liver graft preserved with normothermic machine perfusion or sequential hypothermic- normothermic machine perfusion (SHNMP). * Signed and dated informed consent prior study inclusion.
Exclusion criteria
* Pediatric patients (age \< 18 years) * Patients undergoing re-transplantation (history of previous liver transplantation) * Patients with acute liver failure * Patients undergoing multi-organ transplantation (e.g., liver-kidney, liver-heart) * Temporarily unconscious patients * Patients unable to freely express consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Allograft Dysfunction (EAD) | Within 7 days after liver transplantation | Incidence of Early Allograft Dysfunction (EAD), defined according to the Olthoff criteria as bilirubin ≥10 mg/dL or INR ≥1.6 on postoperative day 7, or AST/ALT \>2000 IU/L within the first 7 postoperative days. |
Countries
Italy
Contacts
CONTACTSalvatore Gruttadauria
CONTACTMonica Rizzo
Outcome results
None listed