Efficacy and Safety Study of Everolimus Plus Reduced Cyclosporine Versus Mycophenolic Acid Plus Cyclosporine in Kidney Transplant Recipients

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00251004
• Other study ID #: CRAD001A2309
• Status: Completed
• Phase: Phase 3
• First received: November 7, 2005
• Last updated: April 7, 2011
• Start date: October 2005
• Est. completion date: October 2009

Study information

• Verified date: April 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to compare the safety and efficacy of three immunosuppressive treatment regimens following a kidney transplant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 833
• Est. completion date: October 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Rejection
• Kidney Transplantation

Intervention

Drug:
• Everolimus
oral, bis in diem/twice a day (bid)
• Mycophenolic Acid (MPA)
2 oral capsules of mycophenolic acid 360mg administered bid
• Cyclosporine A (CsA)
CsA dose adjustments were based on CsA trough levels (C0).
• Basiliximab
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.
• Corticosteroids
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.

Locations

Country	Name	City	State
United States	Novartis	East Hanover	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	Percentage of Participants With the Composite Incidence of Graft Loss, Death or Loss to Follow up at 12 Months Post-transplantation	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.	12 months	Yes
Secondary	Non-inferiority Analysis of Renal Function, Calculated by Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula	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	at 12 months	No