This multicentre, prospective, randomized, open-label study will compare the safety and efficacy of mycophenolate mofetil with delayed introduction of sirolimus and discontinuation of cyclosporine, with those of mycophenolate mofetil and long term continuation of cyclosporine in renal transplant recipients receiving daclizumab (Zenapax) as induction treatment and followed by 8 month treatment with corticosteroids. The anticipated time on study treatment is 12 months. Participants who will complete the initial 12-month study and who will provide written informed consent will be eligible to participate in a 60-month follow-up phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
237
Cyclosporine tablets orally once daily at dose level adapted to maintain concentration at 2 hours after administration (C2): 1000-1500 nanogram per milliliter (ng/mL) during Day 0 to Week 4, and 800-1200 ng/mL during Week 4 to Week 52. For Mycophenoate Mofetil + Sirolimus treatment arm, at Week 12, dose of cyclosporine will be reduced by 50% for 3 days, followed by 1/4 of the dose for 3 days, and then cyclosporine will be stopped.
Daclizumab 2 milligram (mg) per kilogram (kg) will be administered as intravenous infusion over 15 minute on Day 0 (during the 24 hours preceding renal transplantation) and at a dose of 1 mg/kg on Day14.
Mycophenoate mofetil 1 gram (g) (2\*500mg tablets or 4\*250mg capsules) will be given twice daily (daily dose of 2 g) orally for 12 months.
Prednisolone 250 mg intravenously on Day 0, followed by 0.5 mg/kg orally daily (maximum 40 mg daily) from Day 1 to Day 7, then 0.25 mg/kg orally daily (maximum 20 mg daily), then dose will be stepwise reduced by 2.5 mg per week to reach to a dose level of 10 mg daily and continued up to 6 months and finally drug will be discontinued after 8 months.
Sirolimus tablets will be given orally from week 12 to week 52, starting with loading dose of 10 mg daily for 2 days followed by 6 mg daily to adapt to trough concentrations of 8-15 ng/mL from week 12 to week 39, and 5-10 ng/mL from week 39 to week 52.
Unnamed facility
Angers, France
Unnamed facility
Caen, France
Unnamed facility
Clermont-Ferrand, France
Unnamed facility
La Tronche, France
Unnamed facility
Lille, France
Unnamed facility
Limoges, France
Unnamed facility
Lyon, France
Unnamed facility
Paris, France
Unnamed facility
Paris, France
Unnamed facility
Paris, France
...and 7 more locations
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60
Time frame: 60 months
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 12 months
Number of Participants With Serious Adverse Events (SAEs)
Time frame: From 12 months up to 60 months
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Week 52
Time frame: 52 weeks
Number of Participants With Cancers and Lymphoproliferative Syndromes
Time frame: Up to approximately 12 months
Number of Participants With Premature Discontinuations due to Adverse Events (AEs)
Time frame: Up to approximately 12 months
Change From Baseline in 24-Hour Urinary Protein at Week 52
Time frame: 52 weeks
Mean Inverse Creatinine Concentration
Time frame: Week 4, 8, 12, 14, 16, 26, 39, and 52
Creatinine Clearance Calculated and Corrected According to Cockcroft-Gault
Time frame: Week 4, 8, 12, 14, 16, 26, 39, and 52
Glomerular Filtration Rate (GFR) Measured by Iohexol Clearance
Time frame: Baseline, Week 52
Number of Participants with Response to Treatment, Defined as Creatinine Clearance >/=60 mL/min at Week 52
Time frame: Week 52
Number of Participants With Treated Rejections
Time frame: Baseline up to Week 52
Mean Serum Creatinine Concentration
Time frame: Week 4, 8, 12, 14, 16, 26, 39, and 52
Number of Participants With Biopsy-proven Acute Rejections
Time frame: Baseline up to Month 60
Number of Participants With Histologic Evaluation of the Graft
Time frame: Week 52
Number of Participants Who Were Alive
Time frame: Month 60
Number of Participants With Graft Survival
Time frame: Month 60
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