Efficacy and Safety Study of Everolimus Plus Reduced Cyclosporine Versus Mycophenolic Acid Plus Cyclosporine in Kidney Transplant Recipients
Efficacy and Safety Study Comparing Concentration-controlled Everolimus in Two Doses (1.5 and 3.0 mg/Day Starting Doses) With Reduced Cyclosporine Versus 1.44 g Mycophenolic Acid (as Sodium Salt) With Standard Dose Cyclosporine in de Novo Renal Transplant Recipients
1 other identifier
interventional
833
1 country
1
Brief Summary
The purpose of this study was to compare the safety and efficacy of three immunosuppressive treatment regimens following a kidney transplant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2005
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2005
CompletedFirst Submitted
Initial submission to the registry
November 7, 2005
CompletedFirst Posted
Study publicly available on registry
November 9, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2009
CompletedResults Posted
Study results publicly available
May 10, 2011
CompletedMay 10, 2011
April 1, 2011
3.8 years
November 7, 2005
December 17, 2010
April 7, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis
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.
12 months
Non-inferiority Analysis on Percentage of Participants With Composite Efficacy Endpoints
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.
12 months
Secondary Outcomes (2)
Percentage of Participants With the Composite Incidence of Graft Loss, Death or Loss to Follow up at 12 Months Post-transplantation
12 months
Non-inferiority Analysis of Renal Function, Calculated by Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula
at 12 months
Study Arms (3)
Low-dose Everolimus Group
EXPERIMENTAL1.5 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
EXPERIMENTAL3.0 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
ACTIVE COMPARATOR1.44 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.
Interventions
oral, bis in diem/twice a day (bid)
2 oral capsules of mycophenolic acid 360mg administered bid
CsA dose adjustments were based on CsA trough levels (C0).
All patients received two 20 mg doses of basiliximab administered intravenously. The first dose was to be given within 2 hours prior to transplant surgery and the second dose was to be administered on day 4, or each dose could have been administered according to local practice.
Oral corticosteroids were administered according to local practice during the trial. At the same center, all patients were to follow the same steroid administration protocol.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novartislead
Study Sites (1)
Novartis
East Hanover, New Jersey, 07936, United States
Related Publications (3)
Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.
PMID: 39382091DERIVEDCibrik D, Silva HT Jr, Vathsala A, Lackova E, Cornu-Artis C, Walker RG, Wang Z, Zibari GB, Shihab F, Kim YS. Randomized trial of everolimus-facilitated calcineurin inhibitor minimization over 24 months in renal transplantation. Transplantation. 2013 Apr 15;95(7):933-42. doi: 10.1097/TP.0b013e3182848e03.
PMID: 23422495DERIVEDShihab FS, Cibrik D, Chan L, Kim YS, Carmellini M, Walker R, Zibari G, Pattison J, Cornu-Artis C, Wang Z, Tedesco-Silva H Jr. Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine. Clin Transplant. 2013 Mar-Apr;27(2):217-26. doi: 10.1111/ctr.12045. Epub 2012 Dec 12.
PMID: 23230975DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis
Novartis
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
November 7, 2005
First Posted
November 9, 2005
Study Start
October 1, 2005
Primary Completion
August 1, 2009
Study Completion
October 1, 2009
Last Updated
May 10, 2011
Results First Posted
May 10, 2011
Record last verified: 2011-04