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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by Heidelberg University
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Peter Schemmer, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01781195
First received: January 29, 2013
Last updated: NA
Last verified: January 2013
History: No changes posted
  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 Heidelberg University:

Primary Outcome Measures:
  • infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia) [ Time Frame: 1-year follow-up per patient ] [ Designated as safety issue: No ]
    clinical visit: infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)


Secondary Outcome Measures:
  • liver function (LiMAx) [ Time Frame: one week ] [ Designated as safety issue: No ]
    LiMAx test before liver transplantation, and on postoperative days 1, 3, 7

  • HLA-DR status [ Time Frame: one week ] [ Designated as safety issue: No ]
    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: August 2015
Estimated Primary Completion Date: February 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

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01781195

Contacts
Contact: Peter Schemmer, Prof. +49-6221-566205 peter.schemmer@med.uni-heidelberg.de
Contact: Susanne Richter, MD Susanne1.Richter@med.uni-heidelberg.de

Sponsors and Collaborators
Heidelberg University
Astellas Pharma Inc
Investigators
Principal Investigator: Peter Schemmer, Prof. University Hospital Heidelberg
  More Information

No publications provided

Responsible Party: Peter Schemmer, professor, University of Heidelberg
ClinicalTrials.gov Identifier: NCT01781195     History of Changes
Other Study ID Numbers: IMUTECT2013-01
Study First Received: January 29, 2013
Last Updated: January 29, 2013
Health Authority: Germany: Ethics Commission

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

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014