Lowering Total Immunosuppressive Load in Renal Transplant Recipients More Than 12 Months Posttransplant

Study Overview
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Brief Summary
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To compare the change in renal function between CsA or MMF withdrawal from before to 12 months after drug withdrawal in renal transplant recipients on triple immunosuppressive therapy

Detailed Description
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To compare the change in renal function between CsA or MMF withdrawal from before to 12 months after drug withdrawal in renal transplant recipients on triple immunosuppressive therapy. Secondly to examine safety following withdrawal of CsA or MMF, respectively, by the following parameters: Biopsy verified acute rejection episodes, time to first rejection and number of steroid resistant rejection episodes within 12 months. Hematology (Hb, WBC, platelets) abnormalities within 12 months. Graft and patient survival at 12 months and 5 years. Absolute difference in renal function between withdrawal groups at 12 months. Three monthly changes in renal function from drug withdrawal to 12 months. Change in dyslipidemia frequency from drug withdrawal to 12 months. Change in hypertension frequency from drug withdrawal to 12 months. Change in glucose tolerance from drug withdrawal to 12 months. Cumulative incidence of clinical infections resulting in hospitalization within 12 months. Sub protocols will also examine the following aspects: Cardiovascular: Homocysteine. Lipid peroxidation. Microvascular function and vasoactive parameters Quality of life (QoL): ESRD SCL-TM, SF-36 (short version) and EQ-5D (GI-checklist extended) questionnaires will be used. Pharmacoeconomical evaluation.

Official Title
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Lowering Total Immunosuppressive Load in Renal Transplant Recipients More Than 12 Months Posttransplant - Randomised Withdrawal of Mycophenolate Mofetil (CellCept®) or Cyclosporine A (Sandimmun Neoral®)

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Mycophenolate mofetil withdrawal
* Drug: Cyclosporione A withdrawal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients of either gender above 18 years of age at time of randomisation. 2. More than twelve months posttransplant. 3. Treated with an immunosuppressive protocol consisting of CsA, MMF and steroid from the time of discharge from the transplant clinic (e.g. 3 months posttransplant). 4. Kidney (only) transplant recipients with stable renal function (S-creatinine < 300 umol/L and an average increase in S-creatinine < 20% the last 6 months prior to inclusion) and without treated clinically and/or biopsy proven acute rejection episodes the last 6 months prior to inclusion. 5. No previous steroid resistant acute rejections (e.g. treated with ATG/OKT3). 6. Not more than two steroid sensitive acute rejections posttransplant. 7. Signed informed consent. Exclusion Criteria: - 1. PRA positivity > 20%. 2. Concomitant therapy with other investigational drugs or prohibited medication specified in the protocol. 3. Life expectancy less than one year. 4. Acute illness or acute fungal, bacterial or viral infection at screening. 5. Unable and/or unlikely to follow the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Mycophenolate mofetil withdrawal|nan|
|Drug: Cyclosporione A withdrawal|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is the absolute change in renal function from inclusion to 12 months post drug withdrawal, evaluated as GFR estimated from Nankivell's formula B and normalised for 1.73 m2 body-surface. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft and patient survival at 12 months and 5 years posttransplant. |  |  | 
| Proportion of patients with biopsy-proven acute rejection or acute rejection (biopsy proven + presumptive) episodes within 12 months. |  |  | 
| Incidence of HB, WBC, platelet abnormal values requiring clinical intervention within 12 months. |  |  | 
| Incidence of need for additional immunosuppressive therapy at 12 months. |  |  | 
| Absolute difference in renal function between treatment groups at 12 months, evaluated by Nankivell's formula (B). |  |  | 
| Renal function (Nankivell's formula B) development over time (3 monthly) between treatment groups within 12 months. |  |  | 
| Change in dyslipidemia frequency from drug withdrawal to 12 months. |  |  | 
| Change in hypertension frequency from drug withdrawal to 12 months. |  |  | 
| Change in glucose tolerance from drug withdrawal to 12 months. |  |  | 
| Cumulative incidence of clinical infections resulting in hospitalization within 12 months. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcineurin, reduction, immunosuppression, cyclosporine A, mycophenolate mofetil