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

Official Title: “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”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Everolimus (Certican)
• Drug: Cyclosporine (Neoral)
• Drug: Steroid
  • Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
• Drug: Basiliximab (Simulect)

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Everolimus (Certican) with Cyclosporine (Neoral) Continuation
  • 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.
• Experimental: Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal
  • 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.

Primary Measures

• Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula)
  • Time Frame: At Month 3 and Month 12
    Safety Issue?: No

Secondary Measures

• Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up
  • Time Frame: Month 12
    Safety Issue?: No
• Serum Creatinine at Month 6 and 12
  • Time Frame: 6 month and 12 months
    Safety Issue?: No
• Calculated Creatinine Clearance at 6 Month and 12 Month
  • Time Frame: 6 month and 12 months
    Safety Issue?: No
• Safety Based on Adverse Event (AE) Reporting
  • Time Frame: 12 month
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Novartis Study Director Novartis  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00154284

Study ID Number: CRAD001A2419

ClinicalTrials.gov Identifier: NCT00154284

Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios