Delayed CNI-based Immunosuppression With Advagraf After MELD-based Liver Transplantation

Liver Graft Dysfunction Clinical Trial

— IMUTECT  

Official title:

Effect of Delayed CNI-based Immunosuppression With Advagraf on Liver Function After MELD-based Liver Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01781195
• Other study ID #: IMUTECT2013-01
• Status: Recruiting
• Phase: N/A
• First received: January 29, 2013
• Last updated: May 27, 2015
• Start date: February 2013
• Est. completion date: December 2015

Study information

• Verified date: May 2015
• Source: Heidelberg University
• Contact: Peter Schemmer, Prof.
• Phone: +49-6221-566205
• Email: peter.schemmer[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Liver Graft Dysfunction

Locations

Country	Name	City	State
Germany	University Surgical Clinic	Heidelberg

Sponsors (2)

Lead Sponsor	Collaborator
Heidelberg University	Astellas Pharma Inc

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)	clinical visit: infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)	1-year follow-up per patient	No
Secondary	liver function (LiMAx)	LiMAx test before liver transplantation, and on postoperative days 1, 3, 7	one week	No
Secondary	HLA-DR status	HLA-DR status will be measured before liver transplantation and on postoperative days 3, 5, 7.	one week	No