Evaluation of Preimplantation Portal Vein and Hepatic Artery Flushing With Tacrolimus (PATAC)

December 31, 2016 updated by: Republican Scientific and Practical Center for Organ and Tissue Transplantation

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Minsk, Belarus, 220116
        • RSPC for organ and tissue transplantation, Minsk 9th clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tacrolimus + HTK
During back-table operation 1000 ml of HTK solution 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.
Drug: Tacrolimus
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
No Intervention: HTK
During back-table operation 1000 ml of HTK solution cooled to 2-4˚C 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 under gravity pressure of 40 cm H2O.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1-7 postoperative days after liver transplant procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
liver biopsy taken at 2 hours after portal reperfusion
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.
0 and 20 min after portal reperfusion, 1 and 3 postoperative day
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.
15 min and 2 hours after portal reperfusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Republican Scientific and Practical Center for Organ and Tissue Transplantation

Investigators

  • Principal Investigator: Aliaksei E Shcherba, PhD, RSPC for tissue and organ transplantation
  • Study Chair: Oleg O Rumo, MD PhD, RSPC for organ and tissue transplantation, Minsk 9th clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

April 6, 2013

First Submitted That Met QC Criteria

June 22, 2013

First Posted (Estimate)

June 26, 2013

Study Record Updates

Last Update Posted (Actual)

February 23, 2017

Last Update Submitted That Met QC Criteria

December 31, 2016

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1633

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Clinical Study Report
    Information identifier: 10.15825/1995-1191-2015-3-24
  2. Clinical Study Report
    Information identifier: 10.21614/jtmr-21-2-82

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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