Clinical trial NCT01887171: Evaluation of Preimplantation Portal Vein and Hepatic Artery Flushing With Tacrolimus
Official title: A Randomized Study of Effect of Preimplantation Portal Vein and Hepatic Artery Liver Flushing With Tacrolimus on Ischemia-reperfusion Injury, Allograft Dysfunction and Liver Histology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Early Allograft Dysfunction
Ischemic Reperfusion Injury
Liver Transplantation
Hyperfibrinolysis
Keywords: Liver transplantation
Early allograft dysfunction
Ischemic reperfusion injury
Portal and arterial ex vivo HTK flush
Lead sponsor: Republican Scientific and Practical Center for Organ and Tissue Transplantation
Sponsor class: OTHER
First posted: 2013-06-26
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether the Tacrolimus added to histidine-tryptophan-ketoglutarate (HTK) solution given through intraportal and intraarterial infusion during back-table procedure is capable of reducing the degree of early allograft liver dysfunction, as assessed by postoperative levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), during first 7 postoperative days and by serum and histochemical markers of liver injury and inflammation.

Detailed description: Early allograft liver dysfunction remains a significant complication of cadaveric liver transplantation with resource consuming and costly treatment, increased risk of multiorgan failure and 6-months mortality.

Ischemic reperfusion injury (IRI) is a main reason for early allograft liver dysfunction. Inflammatory response to brain death in donor can precipitate the extent of dysfunction after reperfusion in recipient (1). Clear inflammatory pathways in response to IRI have been reported to be associated with early allograft liver dysfunction (2,3). It was shown that ex vivo intraportal tacrolimus perfusion suppressed inflammation and immune response in the transplanted liver on a genome-wide basis (4).

We hypothesize that Tacrolimus added to HTK solution given through intraportal and intraarterial back-table infusion is capable of reducing the degree of early allograft liver dysfunction, as assessed by incidence of postreperfusion hyperfibrinolysis, postoperative levels of AST,ALT, during 1-7 postoperative days as well as serum and histochemical markers of liver injury and inflammation compared to no intraportal and intraarterial back-table infusion.

Eligibility criteria: Inclusion Criteria:

* Donor:

age 15-65 years macrovesicular steatosis \< 40% (macroscopy or biopsy) sodium \<165 mmol/l ICU stay and ventilation \< 11 days cold ischemia time \< 13 hours AST \< 200 U/l ALT \< 200 U/l bilirubin \< 50 μmol/l application of norepinephrine is allowed

* Recipient age: 18-69

Exclusion Criteria:

Recipient:

* live donor liver transplant
* reduced and split grafts
* multi organ failure

Primary outcomes:
measure: Early Allograft Dysfunction
timeFrame: 1-7 postoperative days after liver transplant procedure
Secondary outcomes:
measure: Ischemic Reperfusion Injury of the Liver Allograft
timeFrame: liver biopsy taken at 2 hours after portal reperfusion
measure: Inflammatory Response to Reperfusion
timeFrame: 0 and 20 min after portal reperfusion, 1 and 3 postoperative day
measure: Postreperfusion Hyperfibrinolysis
timeFrame: 15 min and 2 hours after portal reperfusion
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: RSPC for organ and tissue transplantation, Minsk 9th clinic
Study officials:
affiliation: RSPC for tissue and organ transplantation
name: Aliaksei E Shcherba, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: RSPC for organ and tissue transplantation, Minsk 9th clinic
name: Oleg O Rumo, MD PhD
role: STUDY_CHAIR
References:
citation: Friedman BH, Wolf JH, Wang L, Putt ME, Shaked A, Christie JD, Hancock WW, Olthoff KM. Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation. Liver Transpl. 2012 Feb;18(2):166-76. doi: 10.1002/lt.22451.
citation: Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl. 2003 Jul;9(7):651-63. doi: 10.1053/jlts.2003.50105.
citation: Ilmakunnas M, Tukiainen EM, Rouhiainen A, Rauvala H, Arola J, Nordin A, Makisalo H, Hockerstedt K, Isoniemi H. High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation. Liver Transpl. 2008 Oct;14(10):1517-25. doi: 10.1002/lt.21573.
citation: Kristo I, Wilflingseder J, Kainz A, Marschalek J, Wekerle T, Muhlbacher F, Oberbauer R, Bodingbauer M. Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial. Transpl Int. 2011 Sep;24(9):912-9. doi: 10.1111/j.1432-2277.2011.01284.x. Epub 2011 Jun 14.
citation: Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.
citation: Shcherba A.E., Minou A.F., Efimov D.J., Korotkov S.V., LebedzO.A., Dzyadzko A.M., Karitka A., Santotski E.O., Rummo O.O.//Influence of Back Table Portal And Arterial Flushing with HTK and Tacrolimus on the Incidence of Liver Graft Dysfunction. Materials of "Avantguardia in the HPB - surgery and Liver transplantation: When East meets West". Volume 61, June 2014, Supplement 1.- P. S13-14.
citation: Abstracts of the ILTS 20(th) Annual International Congress, June 3-7, 2014, London, United Kingdom. Liver Transpl. 2014 Jun;20 Suppl 1:S1-399. doi: 10.1002/lt.23901. No abstract available.