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
Overview
- Phase
- Phase 3
- Intervention
- Everolimus (Certican)
- Conditions
- Organ Transplantation, Renal Transplantation
- Sponsor
- Novartis
- Enrollment
- 114
- Primary Endpoint
- Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
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.
Intervention: Everolimus (Certican)
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.
Intervention: Cyclosporine (Neoral)
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.
Intervention: Steroid
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.
Intervention: Basiliximab (Simulect)
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.
Intervention: Everolimus (Certican)
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.
Intervention: Cyclosporine (Neoral)
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.
Intervention: Steroid
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.
Intervention: Basiliximab (Simulect)
Outcomes
Primary Outcomes
Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula)
Time Frame: At Month 3 and Month 12
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 \[mL/min\].
Secondary Outcomes
- Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up(Month 12)
- Serum Creatinine at Month 6 and 12(6 month and 12 months)
- Calculated Creatinine Clearance at 6 Month and 12 Month(6 month and 12 months)