Evaluation of the Therapeutic Benefit of an Initial Intensified Dosing Regimen of Mycophenolate Sodium Versus a Standard Regimen in Renal Transplant Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if an initial intensified enteric-coated mycophenolate sodium (Myfortic) dosing regimen administered during the first six weeks post renal transplantation provides improved efficacy, with a similar safety profile, compared to a standard regimen of Myfortic.

Official Title
-----------------
A Randomized, Multicenter, Parallel-group, Open-label Study to Evaluate the Therapeutic Benefit of an Initially Intensified Dosing Regimen of Mycophenolate Sodium Versus a Standard Dosing Regimen, in Combination With Cyclosporine and Corticosteroids in de Novo Renal Transplant Patients

Conditions
-----------------
Kidney Transplantation

Intervention / Treatment
-----------------
* Drug: Enteric-coated mycophenolate sodium (Myfortic)
* Drug: Cyclosporine (Neoral)
* Drug: Prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females, 18 to 65 years old First or second time kidney transplant patients For females capable of becoming pregnant, negative pregnancy test prior to entry into trial and effective birth control during trial and 3 months after stopping trial medication Exclusion Criteria: Previous graft loss due to immunological reasons in the 1st year after the 1st transplant Multi-organ recipients or previous transplant of another organ, different from the kidney Recipients from a non-heart-beating donor Known hypersensitivity to mycophenolic acid or cyclosporine HIV positive or Hepatitis B surface antigen positive History of malignancy (past 5 years) Pregnancy or planned pregnancy, lactating, or unwillingness to use effective contraception. Evidence of severe liver disease Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensified Mycophenolate Sodium (Myfortic) dosing regimen<br>In patients randomized to the intensified Myfortic dosing regimen, the initial dose was 2-fold of the labeled dose (i.e. 2880 mg/day). The dosage was reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment. | Drug: Enteric-coated mycophenolate sodium (Myfortic)<br>* 1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.<br>Drug: Cyclosporine (Neoral)<br>* cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels<br>Drug: Prednisone<br>* 20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.<br>|
| Active Comparator: Standard Mycophenolate Sodium (Myfortic) dosing regimen<br>In patients randomized to the standard Myfortic dosing regimen, the initial dose of 1440 mg/day had to be maintained throughout the whole study. | Drug: Enteric-coated mycophenolate sodium (Myfortic)<br>* 1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.<br>Drug: Cyclosporine (Neoral)<br>* cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels<br>Drug: Prednisone<br>* 20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death | To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection [BPAR], graft loss [GFL] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | The overall treatment differences of the number of participants with at least one occurrence of the composite event BPAR, GFL or death at study days 21 and 84 post-transplantation. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.) | 21 and 84 days | 
| Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the GFR. Serum creatinine levels, age, sex and race were used to estimate the GFR levels in mL/min/1.73m^2. | at 21 days, 84 days and 180 days | 
| Renal Function Assessed by Serum Creatinine at Each Visits |  | at 21 days, 84 days and 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal, Kidney, Intensified, Enteric-coated mycophenolate sodium, Transplant