Clinical trial NCT01023815
Conditions: de Novo Kidney Transplant Recipients Renal Transplantation
Keywords: Immunosuppression renal transplantation once-a-day regimen steroid withdrawal drug minimization immunosuppression for prevention of acute rejections
Sponsor: Novartis
Start date: 2009-04-01; Completion date: 2012-07-01
Enrollment: 330 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:

Arms: arm 1: Everolimus: in patients randomized to Group A before Amendment 1 approval, from the day following randomization, the whole daily dose of everolimus was taken in the morning, at the same time of the CsA and steroid dosing. At the Rand+1W visit, the everolimus dose was adjusted to reach and maintain everolimus blood levels between 5 and 8 ng/mL until end of Month 12.

Cyclosporine: in patients randomized to Group A before Amendment 1 approval, from the day following randomization, the whole cyclosporine daily dose was taken in the morning. The dose was then adjusted to maintain C2 levels between 350 and 700 ng/mL.

Prednisone: In patients randomized to Group A before Amendment 1 approval, the dose of prednisone was kept stable at 5 mg/day in the morning. arm 2: Everolimus: after randomization the everolimus dose was adjusted, if necessary, to maintain a C0 within 6-10 ng/mL until M12.

Cyclosporine:after randomization the cyclosporine dose was adjusted to maintain CsA C2 levels within 300-500 ng/mL until M12.

Prednisone: starting from Visit 5 (day 90 ± 28 days), oral prednisone was tapered until complete stop. It was recommended to taper prednisone by 1 mg/week until complete stop in 5 to 6 weeks. arm 3: Everolimus: after randomization the everolimus dose was adjusted, if necessary, in order to maintain a C0 within 6-10 ng/mL until M12.

Cyclosporine: after randomization the cyclosporine dose was gradually adjusted to reach and maintain C2 blood levels of 200-450 ng/mL between Month 6 and Month 12.

Prednisone: the dose of prednisone was kept stable at 5 mg/day in the morning. arm 4: NRP defined in whom a renal transplantation was performed, received at least one dose of study drug (everolimus) but who did not qualify for randomization at Visit 5, Day 90. This group was addressed as "not randomized patients" (NRP) and described with respect to baseline characteristics, treatment and outcome variables.
Interventions: intervention 1: everolimus intervention 2: cyclosporine intervention 3: Prednison (continuous steroids)
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: continuous steroids

Protocol documents: