NCT01887171

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
86

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jul 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 6, 2013

Completed
3 months until next milestone

First Posted

Study publicly available on registry

June 26, 2013

Completed
5 days until next milestone

Study Start

First participant enrolled

July 1, 2013

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
2.7 years until next milestone

Results Posted

Study results publicly available

February 23, 2017

Completed
Last Updated

February 23, 2017

Status Verified

November 1, 2014

Enrollment Period

1 year

First QC Date

April 6, 2013

Results QC Date

December 31, 2016

Last Update Submit

December 31, 2016

Conditions

Early Allograft DysfunctionIschemic Reperfusion InjuryLiver TransplantationHyperfibrinolysis

Keywords

Liver transplantationEarly allograft dysfunctionIschemic reperfusion injuryPortal and arterial ex vivo HTK flush

Outcome Measures

Primary Outcomes (1)

  • Early Allograft Dysfunction

    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 Outcomes (3)

  • Ischemic Reperfusion Injury of the Liver Allograft

    liver biopsy taken at 2 hours after portal reperfusion

  • Inflammatory Response to Reperfusion

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

  • Postreperfusion Hyperfibrinolysis

    15 min and 2 hours after portal reperfusion

Study Arms (2)

Tacrolimus + HTK

EXPERIMENTAL

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

HTK

NO INTERVENTION

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.

Interventions

TacrolimusDRUG

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.

Also known as: Tacrolimus, Astellas Pharma Europe, Custodiol, Dr. Franz Köhler Chemie GmBH
Tacrolimus + HTK

Eligibility Criteria

Age18 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Recipient:
  • live donor liver transplant
  • reduced and split grafts
  • multi organ failure

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

RSPC for organ and tissue transplantation, Minsk 9th clinic

Minsk, 220116, Belarus

Location

Related Publications (7)

  • 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.

    PMID: 22006860BACKGROUND

  • 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.

    PMID: 12827549BACKGROUND

  • 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.

    PMID: 18825712BACKGROUND

  • 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.

    PMID: 21672049BACKGROUND

  • 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.

    PMID: 20677285BACKGROUND

  • 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.

    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.

    PMID: 25044812RESULT

Related Links

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Results Point of Contact

Title
Aliaksej Shcherba
Organization
Republican scientific and practical center for organ and tissue transplantation
aleina@tut.by
+375293330689

Study Officials

  • Aliaksei E Shcherba, PhD

    RSPC for tissue and organ transplantation

    PRINCIPAL INVESTIGATOR

  • Oleg O Rumo, MD PhD

    RSPC for organ and tissue transplantation, Minsk 9th clinic

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 6, 2013

First Posted

June 26, 2013

Study Start

July 1, 2013

Primary Completion

July 1, 2014

Study Completion

July 1, 2014

Last Updated

February 23, 2017

Results First Posted

February 23, 2017

Record last verified: 2014-11

Locations

BE(1)