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Terminal Liver DiseasePhase 2/3TOPNCT01564095

TOP-Study (Tacrolimus Organ Perfusion): Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion

A Phase 2/3 study testing Tacrolimus in people with Terminal Liver Disease and Ischemia Reperfusion Injury, run by Ludwig-Maximilians - University of Munich at 7 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Utilisation of extended criteria donors due to critical organ shortage contributes to increased ischemia reperfusion injury as well as mortality following liver transplantation. Experimental data show protective effects on hepatic ischemia reperfusion injury (IRI) using the calcineurin inhibitor Tacrolimus applied… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tacrolimus
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
7 sitesGermany
Study dates
Oct 2011to Jul 2013
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Recipient:
  • Chronical terminal liver failure, age > 18 years, first organ transplantation
  • Donor:
  • donor age > 65 Jahre
  • macrovesicular steatosis > 40% (macroscopy or biopsy)
  • BMI > 30
Show all 13Show fewer
  • sodium >165 mmol/l
  • ICU stay and ventilation > 7 days
  • cold ischemia time > 13 hours
  • AST > 99 U/l
  • ALT > 105 U/l
  • bilirubin > 3 mg/dl (> 51 µmol/l)
  • application of epinephrine

Who cannot join

  • Donor:
  • Hepatitis B- or Hepatitis C-infection
  • Recipient:
  • Multi organ transplantation
  • high urgency listing
  • extrahepatic tumor disease
  • pregnancy

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow-Klinikum

    Berlin, 13353

  • Department of General and Visceral Surgery, Johann Wolfgang Goethe-University

    Frankfurt am Main, 60596

  • Department of General, Visceral and Transplantation Surgery, Ruprecht Karls University

    Heidelberg, 69120

  • Department of Transplantation Surgery, Johannes Gutenberg University

    Mainz, 55131

  • Ludwig-Maximilians University, Campus Grosshadern, Department of Surgery

    Munich, 81377

  • Department of Surgery, University of Regensburg

    Regensburg, 93053

  • Department of General, Visceral and Transplantation Surgery, Eberhard Karls University

    Tübingen, 72076

Other trials in Germany

About this study

Official title: TOP-Study (Tacrolimus Organ Perfusion): A Prospective Multicenter Trial for Treatment of Ischemia Reperfusion Injury in Marginal Organs With an ex Vivo Tacrolimus Perfusion

Utilisation of extended criteria donors due to critical organ shortage contributes to increased ischemia reperfusion injury as well as mortality following liver transplantation. Experimental data show protective effects on hepatic ischemia reperfusion injury (IRI) using the calcineurin inhibitor Tacrolimus applied intravenously or directly as a hepatic rinse. Moreover clinical data indicate a protective role of a Tacrolimus rinse in human liver transplantation when using normal, healthy grafts. The effects of Tacrolimus on hepatic injury in extended donor criteria (EDC) liver grafts remain unclear. Therefore, the aim of the present study is to examine the effects of a Tacrolimus ex vivo rinse (20 ng/ml) on cellular injury after transplantation of marginal liver grafts exhibiting 2 or more EDCs according to Eurotransplant's definition of EDC grafts.

Being tested
Tacrolimus, HTK/Placebo
Keywords
Liver transplantation, EDC, IRI, graft survival, graft function, graft preconditioning, Tacrolimus rinse, randomised multicenter trial
Medical subject headings
Reperfusion Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TacrolimusDrug

    Also called Tacrolimus, Prograf; Astellas Germany, HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany

    Marginal liver grafts are flushed with Tacrolimus (20ng/ml) solved in 1000 ml HTK preservation solution (duration: 15 min) ex vivo at the end of backtable preparation in the experimental group.

  • HTK/PlaceboDrug

    Also called HTK, histidin-tryptophane-ketoglurate organ preservation solution, Custodiol, Dr. Franz Köhler Chemie, Germany

    Marginal liver grafts are flushed with 1000 ml HTK preservation solution(duration: 15 min) ex vivo at the end of backtable preparation in the placebo group.

Study groups in NCT01564095
Study groupRoleWhat they receive
Tacrolimus + HTKExperimentalEx vivo Tacrolimus Rinse (20 ng/ml solved in 1000 ml HTK) of marginal liver grafts prior to implantation
Receives: Drug: Tacrolimus
HTKPlacebo comparatorEx vivo Rinse (1000 ml HTK) of marginal liver grafts prior to implantation
Receives: Drug: HTK/Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum serum ALT-level

    Measured: 48 hrs following liver transplantation

Secondary outcomes (5)

  1. ALT

    Measured: 1,2,4,7 days after surgery

  2. Graft survival

    Measured: 7 days

  3. AST

    Measured: 1,2,4,7 days after surgery

  4. Bilirubin

    Measured: 1,2,4,7 days after surgery

  5. Creatinin

    Measured: 1,2,4,7 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2012 (estimated)
  2. Study startOct 2011
  3. Primary completionJul 2013
  4. Study completionJul 2013

Why it stopped: Missing evidence of the effectiveness of the study medication

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01564095
Sponsor's protocol ID
TOP-Study
Acronym
TOP
Status last verified
Mar 2017
First submitted
14 Mar 2012
Last updated
23 Mar 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pratschke S, Bilzer M, Grutzner U, Angele M, Tufman A, Jauch KW, Schauer RJ. Tacrolimus preconditioning of rat liver allografts impacts glutathione homeostasis and early reperfusion injury. J Surg Res. 2012 Jul;176(1):309-16. doi: 10.1016/j.jss.2011.07.045. Epub 2011 Aug 25.

    PubMed 21962731

  • St Peter SD, Post DJ, Rodriguez-Davalos MI, Douglas DD, Moss AA, Mulligan DC. Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation. Liver Transpl. 2003 Feb;9(2):144-9. doi: 10.1053/jlts.2003.50018.

    PubMed 12548508

  • 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.

    PubMed 21672049

  • Pratschke S, Arnold H, Zollner A, Heise M, Pascher A, Schemmer P, Scherer MN, Bauer A, Jauch KW, Werner J, Guba M, Angele MK. Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers. Transplant Direct. 2016 May 4;2(6):e76. doi: 10.1097/TXD.0000000000000588. eCollection 2016 Jun.

    PubMed 27500266

  • Pratschke S, Eder M, Heise M, Nadalin S, Pascher A, Schemmer P, Scherer MN, Ulrich F, Wolters H, Jauch KW, Wohling D, Angele MK. Protocol TOP-Study (tacrolimus organ perfusion): a prospective randomized multicenter trial to reduce ischemia reperfusion injury in transplantation of marginal liver grafts with an ex vivo tacrolimus perfusion. Transplant Res. 2013 Mar 4;2(1):3. doi: 10.1186/2047-1440-2-3.

    PubMed 23497558

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Tacrolimus in people with Terminal Liver Disease and Ischemia Reperfusion Injury, run by Ludwig-Maximilians - University of Munich at 7 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Missing evidence of the effectiveness of the study medication). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum serum ALT-level (time frame: 48 hrs following liver transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01564095, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2017.

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