MMF and Calcineurin Inhibitor Withdrawal in CAN

University Hospital Muenster

Status

Terminated

Conditions

Immunosuppressive Agents

Kidney Transplantation

Kidney Failure, Chronic

Treatments

Drug: mycophenolate mofetil (drug)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00204230

Details and patient eligibility

About

Prospective, randomised study: Effect of mycophenolatmofetil (MMF) and CNI withdrawal in patients with histologically proven chronic allograft nephropathy Indication: change in immunosuppressive treatment of chronic allograft nephropathy (CAN)after renal transplantation Hypothesis: Antimetabolite MMF is able to stop progression of CAN and improve blood pressure/ metabolic parameters and structural vessel wall changes

Primary Target:effects of CNI withdrawal and MMF on renal function: stabilisation and/or improvement Secondary Targets: Incidence of adverse events Evaluation of the calcineurin inhibitor free MMF treatment effects on blood pressure, lipids, glucose metabolism and on structural and functional vesselwallchanges Method:open prospective, randomized two-tailed, monocentric study

Full description

Prospective, randomised study: Effect of mycophenolatmofetil in patients with histologically proven chronic allograft nephropathy

SYNOPSIS

Indication: change in treatment to improve the course of chronic allograft nephropathy

Method: open prospective, randomized two-tailed, non blinded monocentric study

Follow up period: 35 Weeks

Number of patients: 2 x 86 patients

Inclusion criteria: • Written informed consent

Reduction of graft function: Increase of serum creatinine >/= 0,1mg/dl/month in the previous 6 months before start of the study and/or new occurrence or increasing proteinuria in the last 6 months before start of the study
Serum creatinine < 4 mg/dl
Biopsy within the last 3 months
histologically proved chronic allograft nephropathy (graft glomerulopathy, chronic rejection ,interstitial fibrosis, tubular atrophy, vascular arteriosclerosis,hyalinosis)
>1 year after renal allografting
At least 5 mg/day of prednisolone or equivalent dose

Exclusion criteria: • Malignomas

Gravidity or Lactation
Participation in other studies
Severe infections
Florid gastrointestinal Ulcer
Age between 18 and 70 years
Leukopenia with less that 3000/l leucocytes, Anaemia Hb  9 g/dl
Therapy with mycophenolatmofetil in the past 6 months
Acute rejections in the apst 6 months

Study protocol:

Phase I: Week 1.-3. Conversion to Triple-Drug-Therapy, consisting of Mycophenolatmofetil, corticosteroids (e.g. prednisolone) and ciclosporine A or Tacrolimus

Addition of Mycophenolatmofetil (MMF) to the previous immosuppressive treatment, consisting of ciclosporine A (CsA) or Tacrolimus (FK506) in combination with corticosteroids, e.g. prednisolone (P). In the case that azathioprine (AZA) had been given, AZA is replaced by MMF. The therapy with MMF starts 3 days after the elimination of azathioprine.

The addition of MMF follows the following scheme if nothing else is indicated:

week: 1g/day, 2.week: 1,5g/day, 3.week: 2g/day
Ciclosporine A bzw. tacrolimus: Target whole trough blood levels:

CsA: 80-120 ng/ml (HPLC) FK506: 4-7 ng/ml (IMX Tacrolimus, Abbott)
Corticosteroids, e.g. prednisolone: The previous dosage is continued, but at least 5 mg prednisolone/day (or equivalent) must be given

Phase II: week 4.-9.

Randomisation at the beginning of week 4:

All patients receiving at least 3 x 500 mg MMF per day were randomised as follows Group A: Continuation of the triple therapy Group B: Elimination of CsA bzw. FK506 The ciclosporine A- or tacrolimus-dosage is reduced ba 33% each 2 weeks so that after 6-8 weeks a total elimination of the drugs is reached.

Phase III: week 10.-35.

Continuous therapy with...:

Group A: Triple therapy MMF / CsA bzw. FK506 / Corticosteroids e.g. Prednisolone Group B: Dual therapy MMF / Corticosteroids e.g. Prednisolone

Primary Endpoint:

Comparison of the development of 1/creatinine in both branches 32 weeks after randomization

Secondary Endpoints:

Occurrence of...
- acute rejections
- infections
- malignomas
- gastrointestinal disorders
Blood pressure evolution and number of antihypertensive drugs
Changes concerning the lipid state
Changes concerning the glucose metabolism
Changes in metabolism of uric acid
Comparison of the development of 1/creatinine within each branch 6 months before and 6 months after therapy conversion
Comparison of drop out rate in branches A und B
Pharmacokinetics of mycophenolic acid (MPA) based on a new method of abbreviated area under the curve (AUC) determination
vessel wall changes of the carotid arteries measured by high resolultion ultrasound methods and hemodynamic parameters measured by task force equipment before and 9 month after cni withdrawal and MMF addition

Criteria for study discontinuation:

Sepsis
Occurrence of acute rejections
Graft loss
Other severe adverse events
patients decision

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Written informed consent Reduction of graft function: Increase of serum creatinine >= 0,1mg/dl/month in the previous 6 months before start of the study and/or new occurrence or increasing proteinuria in the last 6 months before start of the study Serum creatinine < 4 mg/dl Biopsy within the last 3 months histologically proved chronic allograft nephropathy >=1 year after renal allografting >=5 mg/day Prednisolone or equivalent dose

Exclusion criteria

Malignomas Gravidity or Lactation Participation in other studies Severe infections gastrointestinal Ulcer Age <18 and >70 years Leukopenia with less that 3000/dl leucocytes, Anaemia Hb > 9 g/dl Therapy with mycophenolatmofetil in the past 6 months Acute rejections in the past 6 months