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

Keywords

• Renal transplantation,
• everolimus,
• immunosuppressants,
• basiliximab,
• cyclosporine microemulsion discontinuation, cyclosporine microemulsion minimization

Lead sponsor

Novartis is the lead sponsor of 714 studies on the registry; none are open to participants now.

Study arms

• 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.

  Drug: Everolimus (Certican) · Drug: Cyclosporine (Neoral) · Drug: Steroid · Drug: Basiliximab (Simulect)

• 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.

  Drug: Everolimus (Certican) · Drug: Cyclosporine (Neoral) · Drug: Steroid · Drug: Basiliximab (Simulect)

Interventions

• DrugEverolimus (Certican)

  Also known as: Certican

• DrugCyclosporine (Neoral)

  Also known as: Neoral

• DrugSteroid

  Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.

  Also known as: Prednisone

• DrugBasiliximab (Simulect)

  Also known as: Simulect

Primary outcomes

1. 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 \[mL/min\].

   Time frame: At Month 3 and Month 12

Secondary outcomes

1. 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.

   Time frame: Month 12

2. Serum Creatinine at Month 6 and 12

   serum creatinine summarized by mean and standard deviation

   Time frame: 6 month and 12 months

3. 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.

   Time frame: 6 month and 12 months

Baseline characteristics

Publications

• Grinyo JM, Paul J, Novoa P, et al. (2010). Better renal function in renal-transplant recipients treated with everolimus plus cyclosporine elimination compared with cyclosporine minimisation, Am J Transplant; 10(Suppl 4): 503: Abstract 1636.