An Open Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Early Calcineurin Inhibitor Withdrawal in Recipients of Primary Renal Allografts Maintained Long-term on Mycophenolate Mofetil (MMF) (CellCept®) and Sirolimus (Rapamune®)
Overview
- Phase
- Phase 4
- Intervention
- Calcineurin inhibitors
- Conditions
- Kidney Transplantation
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 305
- Primary Endpoint
- Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 12
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
This 2-arm study recruited kidney transplant patients who were receiving standard care of calcineurin inhibitors (CNIs, tacrolimus or cyclosporine), CellCept (1.0-1.5 g twice daily) and corticosteroids. They were either randomized to continue this regimen, or CNI therapy was discontinued and replaced by sirolimus therapy (in combination with CellCept and corticosteroids). The effect of these 2 regimens on efficacy, safety and kidney function was evaluated. The anticipated time on study treatment was 1-2 years, and the target sample size was 100-500 individuals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult patients 18-75 years of age
- •Kidney transplant 30-180 days post-transplantation
- •Receipt of cyclosporine or tacrolimus, CellCept, and corticosteroids for greater than 14 days prior to study entry
- •No known contraindications to sirolimus
Exclusion Criteria
- •Multiple organ transplant recipients or secondary kidney transplant recipients
- •Corticosteroid-resistant rejection episode within 90 days prior to study entry or corticosteroid-sensitive rejection episode within 30 days prior to study entry
- •More than 1 biopsy-proven episode of acute rejection prior to study entry
- •Treated with sirolimus before the study
- •Organ transplant or expected organ transplant, other than kidney
- •History of malignancy in the last 5 years (except successfully treated localized non-melanotic skin cancer)
Arms & Interventions
2
Intervention: Calcineurin inhibitors
1
Intervention: mycophenolate mofetil [CellCept]
1
Intervention: Corticosteroids
1
Intervention: Sirolimus
2
Intervention: mycophenolate mofetil [CellCept]
2
Intervention: Corticosteroids
Outcomes
Primary Outcomes
Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 12
Time Frame: baseline to 12 months
The primary efficacy endpoint was mean percent change in renal function from baseline to 12 months postrandomization, as measured by Glomerular Filtration Rate utilizing renal clearance of cold iothalamate. percent change= \[(Glomerular Filtration Rate at Month 12-Glomerular Filtration Rate at baseline)/Glomerular Filtration Rate at baseline\]\*100 percent.
Secondary Outcomes
- Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 24(Baseline to 24 months)
- Mean Percent Change in Serum Creatinine From Baseline to Months 6, 12, and 24(baseline, 6, 12, and 24 months)
- Mean Percent Change in Calculated Creatinine Clearance From Baseline to Months 6, 12, and 24(baseline 6, 12, and 24 months)
- Mean Percent Change in Calculated Glomerular Filtration Rate From Baseline to Months 6, 12, and 24 (Nankivell Equation)(baseline, 6, 12, and 24 months)