- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00204230
MMF and Calcineurin Inhibitor Withdrawal in CAN
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
Study Overview
Status
Intervention / Treatment
Detailed 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
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:
- 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
Study Type
Enrollment
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
-
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
course of renal function over 35 weeks
|
Secondary Outcome Measures
Outcome Measure |
---|
after 35 weeks of follow up:
|
incidence of
|
-acute rejections
|
-infections
|
-malignomas
|
-gastrointestinal disorders
|
development of blood pressure over 35 weeks
|
number of antihypertensive drugs
|
lipid state at entry and after 35 weeks
|
blood glucose ,HBA1c at entry and after 35 weeks
|
uric acid at entry and after 35 weeks
|
Comparison of the development of 1/creatinine within each group at entry and 35 weeks after therapy conversion
|
area under the curve (AUC) determination of mycophenolic acid (MPA)
|
vessel wall changes of the carotid arteries IMD , compliance, distensibility and hemodynamic parameters CO, CI, at entry and after after cni withdrawal and MMF addition
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Barbara M Suwelack, PhD, University Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency, Chronic
- Kidney Failure, Chronic
- Renal Insufficiency
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Mycophenolic Acid
Other Study ID Numbers
- 1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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