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Delayed CNI-based Immunosuppression With Advagraf After MELD-based Liver Transplantation (IMUTECT)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified May 2015 by Peter Schemmer, Heidelberg University.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01781195
First Posted: January 31, 2013
Last Update Posted: May 28, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Peter Schemmer, Heidelberg University
  Purpose
Prolonged-release low-dose Advagraf should better protect from CNI-side effects compared to standard immunosuppressive regiments while the rate of rejection is not increased and thus graft function is well maintained. We hypothesize that especially in high-MELD (MELD-score >20) recipients who have a decreased immune competence the prolonged-release low-dose Advagraf concept would better protect from side effects of immunosuppression (i.e. infection). Nevertheless, we assume that also patients with a MELD-score ≤20 will benefit from this concept in regard to lower infection rates and less side effects of immunosuppression.

Condition
Liver Graft Dysfunction

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of Delayed CNI-based Immunosuppression With Advagraf on Liver Function After MELD-based Liver Transplantation

Resource links provided by NLM:


Further study details as provided by Peter Schemmer, Heidelberg University:

Primary Outcome Measures:
  • infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia) [ Time Frame: 1-year follow-up per patient ]
    clinical visit: infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)


Secondary Outcome Measures:
  • liver function (LiMAx) [ Time Frame: one week ]
    LiMAx test before liver transplantation, and on postoperative days 1, 3, 7

  • HLA-DR status [ Time Frame: one week ]
    HLA-DR status will be measured before liver transplantation and on postoperative days 3, 5, 7.


Biospecimen Retention:   Samples Without DNA
Blood: HLA-DR status

Estimated Enrollment: 50
Study Start Date: February 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Advagraf-based immunosuppression
50 patients after liver transplantation (25 with a MELD-score ≤20 and 25 patients with a MELD-score >20) under CNI-based immunosuppression with Advagraf

Detailed Description:

The MELD-score (model of end stage liver disease) was designed to estimate the prognosis after TIPS (transjugular intrahepatic porto-systemic shunt). Nowadays it is the key-score for patients awaiting a liver graft and consists of serum-creatinine, serum-bilirubine and the INR-ratio with values between 6-40. The MELD-based liver allocation follows the sickest patient first strategy which significantly decreased outcome after liver transplantation (LTx) in Germany. There is evidence that the immune competence of very sick patients is decreased. Monocytic HLA-DR status is a marker for the function of the immune system. A reduced monocytic HLA-DR expression is indicative for a suppressed immune system.

Blood levels of Advagraf are slowly increased during the first week until the aimed tacrolimus trough levels are reached. Since therapeutic tacrolimus trough levels are reached not before the end of the first week after transplantation this is a concept for prolonged-release immunosuppression.

We assume, that high-MELD patients (MELD >20) undergoing LTx are immunosuppressed per se. Thus prolonged-release low-dose immunosuppression with Advagraf would decrease both- infection rate (CMV-reactivation, wound infection urinary tract infections, pneumonia, etc.) and side effects of immunosuppression. The immune capacity of patients will be determined by the measurement of monocytic HLA-DR status. To ensure that graft function is not impaired due to rejection episodes, liver function will be determined with the LiMAx-test, a routine procedure in our institution. After 13-C-Methacetin is given to the patient, it is metabolized to paracetamol and 13CO2 by the enzyme CYP1A2 which is localized in hepatocytes. The 13CO2/12CO2 ratio in the exhaled air correlates with liver function.

  Eligibility

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients with different MELD-scores/Na-MELD-scores undergoing liver transplantation
Criteria

Inclusion Criteria:

  • age >18, <65
  • first liver transplantation
  • Immunosuppression with Advagraf, MMF, corticosteroid
  • surgery and postoperative treatment at the department for general-, visceral- and transplantation surgery

Exclusion Criteria:

  • missing informed consent
  • re-transplantation
  • acute infection: CMV (pp65 positive), pneumonia, urinary tract infection, wound infection, reactivation of Hepatitis B/C
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01781195


Contacts
Contact: Peter Schemmer, Prof. +49-6221-566205 peter.schemmer@med.uni-heidelberg.de
Contact: Georgios Polychronidis, MD +4962215637727 Georg.polychronidis@med.uni-heidelberg.de

Locations
Germany
University Surgical Clinic Recruiting
Heidelberg, Germany, 69120
Contact: Peter Schemmer, Prof.    +4962215636500    Peter.schemmer@med.uni-Heidelberg.de   
Contact: Daniela Hall    +4962215636805    Daniela.hall@med.uni-Heidelberg.de   
Sponsors and Collaborators
Heidelberg University
Astellas Pharma Inc
Investigators
Principal Investigator: Peter Schemmer, Prof. University Hospital Heidelberg
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Peter Schemmer, professor, Heidelberg University
ClinicalTrials.gov Identifier: NCT01781195     History of Changes
Other Study ID Numbers: IMUTECT2013-01
First Submitted: January 29, 2013
First Posted: January 31, 2013
Last Update Posted: May 28, 2015
Last Verified: May 2015

Keywords provided by Peter Schemmer, Heidelberg University:
Advagraf
MELD-score
Na-MELD-score
liver function
LiMAx-test
infection rate
HLA-DR status
immunostatus