Evaluation of Preimplantation Portal Vein and Hepatic Artery Flushing With Tacrolimus

NCT ID: NCT01887171

Last Updated: 2017-02-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2014-07-31

Brief Summary

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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

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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.

Conditions

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Early Allograft Dysfunction Ischemic Reperfusion Injury Liver Transplantation Hyperfibrinolysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Caregivers Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Tacrolimus

Intervention Type 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.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Republican Scientific and Practical Center for Organ and Tissue Transplantation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aliaksei E Shcherba, PhD

Role: PRINCIPAL_INVESTIGATOR

RSPC for tissue and organ transplantation

Oleg O Rumo, MD PhD

Role: STUDY_CHAIR

RSPC for organ and tissue transplantation, Minsk 9th clinic

Locations

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RSPC for organ and tissue transplantation, Minsk 9th clinic

Minsk, , Belarus

Site Status

Countries

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Belarus

References

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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.

Reference Type BACKGROUND
PMID: 22006860 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12827549 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18825712 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21672049 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20677285 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT
PMID: 25044812 (View on PubMed)

Study Documents

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Document Type: Clinical Study Report

View Document

Document Type: Clinical Study Report

View Document

Other Identifiers

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1633

Identifier Type: -

Identifier Source: org_study_id

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