MMF and Calcineurin Inhibitor Withdrawal in CAN

NCT ID: NCT00204230

Last Updated: 2005-09-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-10-31
• Study Completion Date: 2002-09-30

Brief Summary

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

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:

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

Conditions

Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation

Keywords

Kidney Failure, Chronic; Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

mycophenolate mofetil (drug)

Intervention Type: DRUG

Eligibility Criteria

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

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• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Principal Investigators

Barbara M Suwelack, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital

References

Suwelack B, Gerhardt U, Hohage H. Withdrawal of cyclosporine or tacrolimus after addition of mycophenolate mofetil in patients with chronic allograft nephropathy. Am J Transplant. 2004 Apr;4(4):655-62. doi: 10.1111/j.1600-6143.2004.00404.x.

Reference Type: RESULT

PMID: 15023160 (View on PubMed)

Other Identifiers

1

Identifier Type: -

Identifier Source: org_study_id