Everolimus in a Cyclosporine Microemulsion-free Regimen Compared to a Low-dose Cyclosporine Microemulsion Regimen, in de Novo Kidney Transplant Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of everolimus in combination with basiliximab, and steroids with and without cyclosporine microemulsion in de novo kidney transplant recipients.

Detailed Description
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This is a combined analysis using 81 patients randomized and treated in CRAD001A2419 (NCT00154284) with 33 randomized and treated in CRAD001A2423 (NCT00170807). This approach is reflected in the protocol amendments for each study, and the one clinical study report for both.

Official Title
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A 12 Month, Multicenter, Randomized, Parallel, Open-label Study, to Evaluate Renal Function and Efficacy of Everolimus With Basiliximab and Cyclosporine Microemulsion Discontinuation at 3 Month Post-transplant Versus Minimization, in de Novo Kidney Transplant Recipients

Conditions
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Organ Transplantation, Renal Transplantation

Intervention / Treatment
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* Drug: Everolimus (Certican)
* Drug: Cyclosporine (Neoral)
* Drug: Steroid
* Drug: Basiliximab (Simulect)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipients of a first renal transplant from a primary cadaveric or non-HLA identical living related donor. Renal cold ischemic time < 36 hours. Age of donor < 65 years. Exclusion Criteria: Patients who have received an investigational drug within 4 weeks of baseline period. Patients who are recipients of multiple organ transplants, including any organ other than kidney. Recipients of non-heart beating donor organs. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Everolimus (Certican) with Cyclosporine (Neoral) Continuation<br>Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice. | Drug: Everolimus (Certican)<br> <br> * Other names: Certican;Drug: Cyclosporine (Neoral)<br> <br> * Other names: Neoral;Drug: Steroid<br>* Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.<br>* Other names: Prednisone;Drug: Basiliximab (Simulect)<br> <br> * Other names: Simulect;|
| Experimental: Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal<br>Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice. | Drug: Everolimus (Certican)<br> <br> * Other names: Certican;Drug: Cyclosporine (Neoral)<br> <br> * Other names: Neoral;Drug: Steroid<br>* Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.<br>* Other names: Prednisone;Drug: Basiliximab (Simulect)<br> <br> * Other names: Simulect;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula) | Nankivell's formula for calculated GFR is shown below: GFR [mL/min] = 6.7/C + W/4 - UREA/2 - 100/H2+ 35 (25 for females). Where W is body weight at specific visit [kg], H is height at specific visit [m], C is the serum concentration of creatinine [mmol/L], and UREA is the serum concentration of urea [mmol/L]. UREA was calculated from blood urea nitrogen (BUN) lab data by: UREA = 2.1441*BUN. If a GFR value from Nankivell formula was less than 10 [mL/min], then the value was assigned as 10 [mL/min]. | At Month 3 and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up | Renal biopsies were collected for all cases of suspected acute rejection. For these cases, regardless of initiation of anti-rejection treatment, a graft core biopsy had been performed within 48 hours. These biopsies were listed on the Kidney Allograft Biopsy eCRF and the results used for patient management for BPAR. Graft loss was defined as the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis as well as re-transplant. BPAR, graft loss, death, or loss to follow-up was analyzed by means of frequency tables. | Month 12 | 
| Serum Creatinine at Month 6 and 12 | serum creatinine summarized by mean and standard deviation | 6 month and 12 months | 
| Calculated Creatinine Clearance at 6 Month and 12 Month | Creatinine clearance calculated by Cockcroft-Gault formula and summarized by mean, and standard deviation. Cockcroft-Gault formula to calculate Creatinine Clearance (CrCl[mL/min]) is shown below: CrCl[mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit [kg], C is the serum concentration of creatinine [mg/dL], R = 1 if the patient is male and = 0.85 if female. | 6 month and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplantation,, everolimus,, immunosuppressants,, basiliximab,, cyclosporine microemulsion discontinuation, cyclosporine microemulsion minimization