Skip to main content
OpenTrials
Completed

NCT Number: NCT01887171

Evaluation of Preimplantation Portal Vein and Hepatic Artery Flushing With Tacrolimus

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Early Allograft Dysfunction Hyperfibrinolysis Ischemic Reperfusion Injury Liver Transplantation

Age range

18 year–69 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

RSPC for organ and tissue transplantation, Minsk 9th clinic

Minsk, 220116, Belarus

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tacrolimus

Drug

1000 ml of HTK solution (Custodiol, Dr. Franz Köhler Chemie GmBH) cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O.

Other names: Tacrolimus, Astellas Pharma Europe, Custodiol, Dr. Franz Köhler Chemie GmBH

Primary outcomes

  1. Early Allograft Dysfunction

    Time frame: 1-7 postoperative days after liver transplant procedure

    Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion.

    Early allograft dysfunction will be assessed on the basis of highest levels of AST and ALT during 1-7 postoperative days.

Secondary outcomes

  1. Ischemic Reperfusion Injury of the Liver Allograft

    Time frame: liver biopsy taken at 2 hours after portal reperfusion

    Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion.

    A wedge resection of small (5x5mm) part of liver segment-III will be sampled at 2 hours after venous reperfusion. Rate of necrosis, inflammation, vascular thrombosis, cluster of differentiation (CD) 68 and High mobility group box 1 protein (HMGB1) staining will be assessed thereafter.

  2. Inflammatory Response to Reperfusion

    Time frame: 0 and 20 min after portal reperfusion, 1 and 3 postoperative day

    Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion.

    After unclamping portal vein but before unclamping the inferior vena cava and after venting of first 100 ml of blood a 5 ml sample of blood (code is "HV") from a tube inserted into caval suture line will be taken. Another 5 ml sample of blood (code is "C") will be taken by puncture of one of hepatic veins 20 min later. Samples (5 ml each) of peripheral blood will be taken on 1st and 3d postoperative day (POD). P-selectin, interleukin-6, interleukin-8, tumor necrosis factor alfa (TNF-a) and macrophage inflammatory protein 1 alpha (MIP-1a) will be determined in samples "HV" and "C". Interleukin-8, elastase, TNF-a and vascular endothelial growth factor (VEGF) will be determined in samples of 1st and 3d POD.

  3. Postreperfusion Hyperfibrinolysis

    Time frame: 15 min and 2 hours after portal reperfusion

    Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion.

    Peripheral blood samples will be taken 15 min and 2 hours after portal reperfusion.

    Hyperfibrinolysis will be diagnosed by Thromboelastometry (ROTEM) if one or more following criteria are met:

    LI30<85% or ML>15% or LI60<85% or A10 in Extem is by 15% is less then A10 in Aptem.

Sponsors and collaborators

Lead sponsor

Republican Scientific and Practical Center for Organ and Tissue Transplantation

Other

Registry information

Official study 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

Acronym: PATAC

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Jun 26, 2013
Registry last updated
Feb 23, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.