Everolimus in a Cyclosporine Microemulsion-free Regimen Compared to a Low-dose Cyclosporine Microemulsion Regimen, in de Novo Kidney Transplant Patients
- Conditions
- Organ Transplantation, Renal Transplantation
- Interventions
- Registration Number
- NCT00154284
- Lead Sponsor
- Novartis
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 114
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Everolimus (Certican) with Cyclosporine (Neoral) Continuation Cyclosporine (Neoral) 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. Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal Basiliximab (Simulect) 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. Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal Cyclosporine (Neoral) 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. Everolimus (Certican) with Cyclosporine (Neoral) Continuation Everolimus (Certican) 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. Everolimus (Certican) with Cyclosporine (Neoral) Continuation Steroid 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. Everolimus (Certican) with Cyclosporine (Neoral) Continuation Basiliximab (Simulect) 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. Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal Everolimus (Certican) 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. Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal Steroid 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 Outcome Measures
Name Time Method Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula) 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 Outcome Measures
Name Time Method Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up Month 12 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.
Serum Creatinine at Month 6 and 12 6 month and 12 months serum creatinine summarized by mean and standard deviation
Calculated Creatinine Clearance at 6 Month and 12 Month 6 month and 12 months 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.