Kidney Transplantation Clinical Trial
Official title:
Randomized Controlled Study: Effect of Mycophenolatmofetil in Patients With Histologically Proven Chronic Allograft Nephropathy
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
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
1. 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:
1. week: 1g/day, 2.week: 1,5g/day, 3.week: 2g/day
2. Ciclosporine A bzw. tacrolimus: Target whole trough blood levels:
CsA: 80-120 ng/ml (HPLC) FK506: 4-7 ng/ml (IMX Tacrolimus, Abbott)
3. 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
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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