This study will compare the following immunosuppressive regimens in recipients of kidney transplantation: A) everolimus, cyclosporine and steroids given once-a-day; B) everolimus and cyclosporine given twice a day with steroid withdrawal; C) everolimus, cyclosporine given twice a day and continuous steroids. The purpose of this study is to evaluate regimens A and B in comparison with the control group (group C) for efficacy, using as main endpoint the treatment failure rate, a composite endpoint including death, graft loss, BPAR and lost to follow-up between randomization and Month 12.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
330
Everolimus (Certican®) was provided in blisters containing tablets of 0.25 mg and 0.75 mg. Everolimus was initiated within 48 hours after graft reperfusion and it was administered orally.
Cyclosporine for microemulsion (CsA, Sandimmun® Neoral®) was coadministered with everolimus at the same time of the day. CsA was available in alu-alu blisters containing soft gelatine capsules of 100 mg, 50 mg, 25 mg and 10 mg. Oral solution, as bottles containing 50 mL of solution (100 mg/mL) has been provided and used in case the drug had been administered to patients by nasogastric tube immediately after transplant.
continuous steroids
Novartis Investigative Site
Perugia, Perugia, Italy
Novartis Investigative Site
Sassari, Sassari, Italy
Novartis Investigative Site
Ancona, Italy
Novartis Investigative Site
Bologna, Italy
Novartis Investigative Site
Brescia, Italy
Novartis Investigative Site
Cagliari, Italy
Novartis Investigative Site
Catania, Italy
Novartis Investigative Site
Coppito, Italy
Novartis Investigative Site
Florence, Italy
Novartis Investigative Site
Genova, Italy
...and 18 more locations
Treatment Failure Rate
Occurrence or not of treatment failure in each patient. Treatment failure was defined as a composite endpoint of biopsy-proven acute rejection (a biopsy graded IA, IB, IIA, IIB or III according to Banff '97 grading with 2007 update), graft loss, death or lost to follow-up occurring after randomization (V5) and within M12 (V9).
Time frame: Between randomization (Month 3) and Month 12
Changes in the Estimated Glomerular Filtration Rate (eGFR) Between Randomization (Month 3) and Month 12
eGFR by Nankivell, in terms of descriptive statistics and change vs randomization visit - to compare the changes in the estimated GFR (Nankivell) between randomization and Month 12 in the steroid withdrawal group (Group B) to the change observed in the standard twice-a-day group (Group C), for non-inferiority
Time frame: Month 3 to Month 12
Biopsy Proven Acute Rejection (BPAR) Rate Between Randomization and Month 12
Occurrence of BPAR (after randomization) between arm B (steroid withdrawal group) and arm c (standard twice-a-day group). BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III according to Banff 1997 grading with 2007 update.
Time frame: Month 3 to Month 12
Number of Participants With Graft and Patient Survival After Randomization
Graft Survival, calculated from the date of transplantation to the date of irreversible graft failure signified by return to long-term retransplantation or the date of the last follow-up during the period when the transplant was still functioning or to the date of death. Patient survival, calculated from the date of transplantation to the date of death or the date of the last follow-up.
Time frame: Month 3 to Month 12
Change in Estimated Creatine Clearance
At each visit, estimated creatinine clearance was measured in the local laboratory to analyze the evolution of the renal function. The following indirect measures of renal function were computed: estimated creatinine clearance according to Cockcroft and Gault formula and MDRD formula.
Time frame: M3, M12
Change in Serum Creatinine
Serum creatinine (a blood measurement) is an important indicator of renal health because it is an easily-measured by-product of muscle metabolism. Measuring serum creatinine is a simple test and it is the most commonly used indicator of renal function.
Time frame: M3, M12
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