Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers.
Pratschke S, Arnold H, et al.Transplantation Direct 2016; 2(6): e76.
Aims
To examine the effects of an ex vivo tacrolimus rinse on ischemia-reperfusion injury (IRI) in transplantation of extended donor criteria (EDC) livers.
Interventions
Participants received randomized organs with either ex vivo perfusion of marginal liver grafts with tacrolimus (20 ng/mL) solved in 1000 mL histidine-tryptophaneketoglutarate (HTK) (tacrolimus + HTK), versus ex vivo perfusion of marginal liver grafts with 1000 mL HTK (HTK-alone).
Participants
24 participants aged > 18 years with end-stage chronic liver disease receiving their first organ transplant.
Outcomes
The primary outcome measured was the maximum alanine transaminase (ALT) level (U/L) within the first 48 hours after liver transplantation. Secondary measured outcomes were postoperative ALT and AST levels (U/L), and graft function.
Follow-up
1 week
CET Conclusions
The study authors hypothesised that an ex vivo flush with tacrolimus could reduce ischaemia reperfusion injury in extended criteria livers. In terms of the primary outcome there was no significant difference in ALT in the first two days. Significantly the study was stopped early after only 25 patients were included (rather than the target of 86). At this stage there was no significant difference in ALT levels in the first 2 days (the primary outcome) but there was an adverse effect of the study drug in terms of AST within the first 7 days; the study was therefore terminated prematurely. The two groups had similar donor and recipient characteristics. Despite some encouraging experimental data, tacrolimus flush ex vivo cannot be recommended for extended criteria livers transplantation.
Data analysis
Modified intention-to-treat analysis
Trial registration
Eudra CT - 2010-021333-31; ClinicalTrials.gov - NCT01564095