Withdrawal of Calcineurin Inhibitors (CNIs) during administration of Mycophenolate Mofetil (MMF) in liver transplant patients suffering adverse effects from CNIs: Study of the reduction in rejection risk by therapeutic drug monitoring of Mycophenolate Mofetil - MiniCept

• Conditions: liver transplant patients suffering adverse effects from treatment with calcineurin inhibitors; MedDRA version: 9.1Level: LLTClassification code 10050434Term: Prophylaxis against liver transplant rejection; MedDRA version: 9.1Level: LLTClassification code 10054980Term: Immunosuppressant drug therapy; MedDRA version: 9.1Level: LLTClassification code 10052538Term: Adverse drug reaction NOS

• Registration Number: EUCTR2007-000789-19-BE
• Lead Sponsor: CHU de Liège, Domaine Universitaire du Sart Tilman

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04-23
• Last Update Posted: 11 November 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1) Male or female patient aged 18 years or older
2) Patient has signed informed consent
3) Patient is able to understand the purpose of the trial
4) First liver transplant or retransplant with delay post-LT of 2 to 10 years
5) Transplantee presenting with adverse effects from anticalcineurins:
- Kidney insufficiency defined by creatinine clearance < 50 ml/mn (calculated or
estimated according to the Cockcroft formula) or a decrease of creatinine
clearance of = 30 ml/mn since transplantation (first month)
- Arterial hypertension not controlled by bitherapy and defined by arterial
pressure of >140/90 measured after 10 min rest in laying position
- Diabetes (Fasting glycaemia > 7.0 mmol/l), whether treated or not
- Neuromuscular toxicity
6) Bitherapy with Cyclosporin and MMF or Tacrolimus and MMF
- Cyclosporin concentration C0 = 100 ng/ml or C2 = 500 ng/ml, OR
- Tacrolimus concentration = 6 ng/ml
7) Liver biopsy performed in the 6 months preceding inclusion for patients with a
post-transplant period of < 5 years and in the 12 months preceding inclusion for
patients with a post-transplant period of > 5 years
8) Negative pregnancy test for women of childbearing potential and reliable
contraception for women of childbearing potential. Contraception must be used
before start of treatment with CellCept, duringf treatment, and 6 weeks after the
last dose of CellCept
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Patient participating in another trial
2) Acute rejection in the 6 months preceding screening
3) History of corticoresistant rejection
4) Chronic rejection
5) Significant ductopenia (absence of interlobular biliary ducts in more than 30 % of
the portal spaces) in the pre-screening graft biopsy.
6) Pre-transplant diabetes (fasting glycaemia > 7.0 mmol/l), whether treated or not,
except for cases of diabetes which resolved after transplantation
7) LT for auto-immune hepatitis or primary sclerosing cholangitis
8) Transplantation due to C virus cirrhosis with reinfection lesions of the
transplanted organ which may require treatment with interferon-ribavirine in the
year following inclusion
9) Contraindications to MMF (Hb < 10g/dl, Neutrophils < 1000/mm3)
10) Immunosuppression with Rapamycin or Azathioprin
11) A woman who is, or might become, pregnant or is lactating
12) Creatinine clearance < 25ml/mn
13) Double liver / kidney trasplant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that in liver transplant patients with side effects of calcineurin inhibitors, withdrawal of these products, followed by MMF monotherapy with therapeutic drug monitoring of MPA, is a reliable approach which does not lead to a significant increase of the risk rejection and which has a positive impact on the side effects of calcineurin inhibitors.;Secondary Objective: To demonstrate that this strategy has a positive impact on the side effects of calcineurin inhibitors without modifying the risk of infection or malignancy.<br><br>To propose an innovative approach of immunosuppression which allows to control the side effects of calcineurin inhibitors without increasing the costs of maintenance immunosuppression;Primary end point(s): Not applicable.