Efficacy and Safety Study of Everolimus Plus Reduced Cyclosporine Versus Mycophenolic Acid Plus Cyclosporine in Kidney Transplant Recipients
Phase 3
Completed
- Conditions
- Kidney TransplantationGraft Rejection
- Interventions
- Drug: Mycophenolic Acid (MPA)Drug: Corticosteroids
- Registration Number
- NCT00251004
- Lead Sponsor
- Novartis
- Brief Summary
The purpose of this study was to compare the safety and efficacy of three immunosuppressive treatment regimens following a kidney transplant.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 833
Inclusion Criteria
- Male and female patients of any race between 18 to 70 years old (inclusive)
- Patients who gave written informed consent to participate in the study
Exclusion Criteria
- Recipients of multi-organ transplantation
- Recipients of a primary cadaveric or primary non-human leucocyte antigen (HLA) identical living donor kidney transplantation.
- Graft cold ischemia time greater than 40 hours.
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low-dose Everolimus Group Cyclosporine A (CsA) 1.5 mg everolimus (one 0.75-mg tablet bis in diem/twice a day (bid)) + basiliximab + reduced-dose Cyclosporine A (CsA) ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Low-dose Everolimus Group Corticosteroids 1.5 mg everolimus (one 0.75-mg tablet bis in diem/twice a day (bid)) + basiliximab + reduced-dose Cyclosporine A (CsA) ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. High-dose Everolimus Group Cyclosporine A (CsA) 3.0 mg everolimus (two 0.75-mg tablets bid) + basiliximab + reduced-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. High-dose Everolimus Group Corticosteroids 3.0 mg everolimus (two 0.75-mg tablets bid) + basiliximab + reduced-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Control Group Mycophenolic Acid (MPA) 1.44 g Mycophenolic Acid (two 360-mg tablets bid) + basiliximab + standard-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a C0 value within the following range for the time of the study: starting at the day 5 visit: 200-300 ng/mL, starting at the month 2 visit and thereafter: 100-250 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Control Group Cyclosporine A (CsA) 1.44 g Mycophenolic Acid (two 360-mg tablets bid) + basiliximab + standard-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a C0 value within the following range for the time of the study: starting at the day 5 visit: 200-300 ng/mL, starting at the month 2 visit and thereafter: 100-250 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Control Group Corticosteroids 1.44 g Mycophenolic Acid (two 360-mg tablets bid) + basiliximab + standard-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a C0 value within the following range for the time of the study: starting at the day 5 visit: 200-300 ng/mL, starting at the month 2 visit and thereafter: 100-250 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Low-dose Everolimus Group Everolimus 1.5 mg everolimus (one 0.75-mg tablet bis in diem/twice a day (bid)) + basiliximab + reduced-dose Cyclosporine A (CsA) ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. High-dose Everolimus Group Everolimus 3.0 mg everolimus (two 0.75-mg tablets bid) + basiliximab + reduced-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Low-dose Everolimus Group Basiliximab 1.5 mg everolimus (one 0.75-mg tablet bis in diem/twice a day (bid)) + basiliximab + reduced-dose Cyclosporine A (CsA) ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. High-dose Everolimus Group Basiliximab 3.0 mg everolimus (two 0.75-mg tablets bid) + basiliximab + reduced-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Control Group Basiliximab 1.44 g Mycophenolic Acid (two 360-mg tablets bid) + basiliximab + standard-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a C0 value within the following range for the time of the study: starting at the day 5 visit: 200-300 ng/mL, starting at the month 2 visit and thereafter: 100-250 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy.
- Primary Outcome Measures
Name Time Method Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis 12 months The primary efficacy endpoint was the 12 month analysis of primary efficacy failure defined as a composite endpoint including treated biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up. A treated BPAR episode was defined as a biopsy graded IA, IB, IIA, IIB, or III that was treated with anti-rejection therapy. 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.
Non-inferiority Analysis on Percentage of Participants With Composite Efficacy Endpoints 12 months The primary efficacy endpoint was the 12 month analysis of primary efficacy failure defined as a composite endpoint including treated biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up. In the definition of composite efficacy failure, loss to follow-up includes patients who did not experience treated BPAR, graft loss or death on or after day 1 and whose last day of contact was prior to day 316, the start day of the 12 month visit window.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With the Composite Incidence of Graft Loss, Death or Loss to Follow up at 12 Months Post-transplantation 12 months Graft loss was defined as graft loss (the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis) and re-transplant.
A loss to follow-up patient in the composite endpoint of graft loss, death or loss to follow-up (the main secondary efficacy endpoint) was a patient who did not experience graft loss or death from day 1 and whose last day of contact was prior to study day 316.Non-inferiority Analysis of Renal Function, Calculated by Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at 12 months Modification of Diet in Renal Disease (MDRD) formula is:
GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where
* C is the serum concentration of creatinine \[mg/dL\],
* A is patient age at sample collection date \[years\],
* G=0.742 when gender is female, otherwise G=1,
* R=1.21 when race is black, otherwise R=1
Trial Locations
- Locations (1)
Novartis
🇺🇸East Hanover, New Jersey, United States