Steroid Withdrawal in Pediatric Renal Transplant Recipients Under Cyclosporine (CyA) and Mycophenolate Mofetil (MMF)

Study Overview
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Brief Summary
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The present study investigates the safety and efficacy of steroid withdrawal in pediatric renal transplant recipients with stable graft function under concomitant immunosuppression with cyclosporine and mycophenolate mofetil.

Detailed Description
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The present protocol aims to investigate the steroid-saving potential of MMF in pediatric patients after NTx. Over a 2-year period, two treatment regimes will be compared in randomized form in patients with a stable renal transplant function in the course of 12 - 24 months after transplantation (controlled first study phase): Branch A: CyA + MMF + withdrawal of steroids over a three-month period following randomization Branch B: CyA + MMF + 4 mg/m² methylprednisolone (or prednisolone equivalent)/day After two years of observation, steroids in the control group (branch B) can be withdrawn optionally in conformity with the same protocol as in branch A (uncontrolled second study phase). It is to be expected that part of the patients will decide in favour of a withdrawal of steroids. In the uncontrolled second study phase, a comparison will thus be drawn among three therapy groups over a period of another 15 months (altogether 3.5 years beginning with randomization), in order to throw some light on the medium-term effect of steroid-free immunosuppression on length growth and transplant function.

Official Title
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Multicenter, Open-label, Randomized Study on Steroid-free Immunosuppression, in Comparison With Daily Steroid Therapy, in Children With Stable Renal Transplant Function Under Cyclosporine (CyA) and Mycophenolate Mofetil (MMF)

Conditions
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Kidney Diseases

Intervention / Treatment
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* Drug: methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 18.0 years Bone age of boys < 15 years, of girls < 13 years Patients 12-24 months after renal transplantation with stable transplant function First or second kidney transplant, living or cadaver kidney donation Triple immunosuppression with cyclosporine (CyA), MMF, and daily steroids at study entry Patients and parents, respectively, have given their written consent after enlightenment (informed consent) Exclusion Criteria: Irreversible rejection of former transplant within 6 months Highly reactive (> 80%) lymphocytotoxic antibodies within 12 months prior to transplantation Anamnestically steroid-resistant rejection of current transplant More than 2 acute rejection reactions prior to study entry (i.e., in the first 12-24 months after kidney transplantation) or 1 acute rejection reaction during the last 6 months before study entry Glomerular filtration rate (GFR) < 40 ml/min/1.73 m² (Schwartz formula) at study entry Acute rejection reaction or unstable transplant function (increase of serum creatinine > 20%) during the last 6 months before study entry or histologically confirmed chronic rejection reaction Suspected insufficient medication compliance Patients receiving a basic immunosuppression other than that prescribed in this protocol Simultaneous therapy with growth hormone after renal transplantation

Ages Eligible for Study
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Maximum 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Steroid withdrawal | Drug: methylprednisolone<br>* withdrawal of methylprednisolone in arm A and continuous Steroid Treatment in arm B<br>|
| Placebo Comparator: B<br>continuos Steroid treatment | Drug: methylprednisolone<br>* withdrawal of methylprednisolone in arm A and continuous Steroid Treatment in arm B<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulation of length growth after 24 months (controlled study phase) and 36 months (uncontrolled study phase) |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who were deprived of steroids successfully |  | 24 months | 
| Transplant survival and function after 24 (controlled) and 36 (uncontrolled) months |  | 24 months | 
| Incidence and severity of steroid side effects |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cyclosporine A, Pediatric renal transplantation, Steroid withdrawal, Mycophenolate Mofetil, Stable graft function, children, renal transplantation