Efficacy and Safety of Everolimus in Combination With Cyclosporine Microemulsion Versus Everolimus in Combination With Enteric-coated Mycophenolate Sodium (EC-MPS), in Adult Renal Transplant Patients in Maintenance.

Study Overview
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Brief Summary
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Efficacy and safety of 2 groups of treatment: everolimus in association with cyclosporine microemulsion and steroids versus everolimus in association with Enteric-coated Mycophenolate Sodium (EC-MPS) and steroids. The study population consists of patients having taken part in study CRAD001A2420 (NCT00154297) until the end (12 months) and having not prematurely discontinued the immunosuppressive regimen received in this study (everolimus + cyclosporine microemulsion + steroids).

Official Title
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A Prospective Multicenter Open-label Randomized Study to Assess Efficacy and Safety of Everolimus in Combination With Cyclosporine Microemulsion Versus Everolimus Without Calcineurine Inhibitor in Combination With Enteric-coated Mycophenolate Sodium (EC-MPS), in Adult Renal Transplant Patients in Maintenance.

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Everolimus + Cyclosporine
* Drug: Everolimus + Enteric-coated Mycophenolate Sodium (EC-MPS)
* Drug: Steroids


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients who participated in and completed study CRAD001A2420 Exclusion criteria: Premature study or study treatment discontinuation in CRAD001A2420 study. Acute rejection within the 3 months prior to inclusion Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Everolimus + Enteric-coated Mycophenolate Sodium (EC-MPS)<br>Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids | Drug: Everolimus + Enteric-coated Mycophenolate Sodium (EC-MPS)<br> <br> * Other names: Myfortic;Drug: Steroids<br> <br> |
| Active Comparator: Everolimus + Cyclosporine<br>Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids | Drug: Everolimus + Cyclosporine<br> <br> * Other names: Neoral;Drug: Steroids<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glomerular Filtration Rate Estimated by Iohexol Plasma Clearance 12 Months After Randomization Between the 2 Groups of Patients. | Primary efficacy endpoint: between treatment analysis of change in iohexol plasmatic clearance (mL/min) from baseline to Month 12 (M12) | From Baseline to Month 12 | 
| Change in the Glomerular Filtration Rate Estimated by Iohexol Plasma Clearance 12 Months After Randomization Between the 2 Groups of Patients Who Completed Trial | Primary efficacy endpoint: between treatment analysis of change in iohexol plasmatic clearance (mL/min) from baseline to Month 12 (M12) | From Baseline to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Renal Function Assessed by Serum Creatinine at Month 3, Month 6 and Month 12 |  | From Baseline to Month 3, 6, and 12 | 
| Number of Participants With Biopsy-proven Acute Rejection (BPAR) at Month 6 and Month 12. |  | Month 6 and 12 | 
| Number of Participants With Treatment Failures Assessed by Biopsy-proven Acute Rejection (BPAR), Graft Loss/Re-transplantation, Death or Lost to Follow-up at Month 12. |  | Month 12 | 
| Change in Renal Function Assessed by Creatinine Clearance at Month 3, Month 6 and Month 12 | Change in creatinine clearance, Nankivell formula (mL/min/1.73m²) from baseline to M12 | From Baseline to Month 3, 6, and 12 | 
| Change in Renal Function Assessed by Proteinuria at Month 3, Month 6 and Month 12 | Change in proteinuria (g/24h) from baseline to M12 | From Baseline to Month 3, 6, and 12 | 
| Assessing Cardiovascular Risk Factors Based on Fasting Glucose. | Blood chemistry - fasting glycemia (mmol/L) | From Baseline to Month 1, 3, 6, 9, and 12 | 
| Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol. | Blood chemistry - total cholesterol (mmol/L) | From Baseline to Month 1, 3, 6, 9, and 12 | 
| Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol. |  | From Baseline to Month 3, 6, and 12 | 
| Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides. |  | From Baseline to Month 1, 3, 6, 9, and 12 | 
| Assessing Cardiovascular Risk Factors Based on Fasting C-reactive Protein (CRP). | Blood chemistry - C-reactive Protein (CRP) (mg/L) | From Baseline to Month 3, 6, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Everolimus, calcineurine inhibitor, renal transplantation in maintenance, chronic allograft nephropathy