Study Comparing Efficacy and Safety of Mycophenolate Mofetil (Cellcept) With Delayed Introduction of Sirolimus and Discontinuation of Cyclosporine, With Those of Mycophenolate Mofetil and Long Term Continuation of Cyclosporine in Renal Transplant Recipients
Phase 3
Completed
- Conditions
- Renal Transplantation
- Interventions
- Registration Number
- NCT02686619
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 237
Inclusion Criteria
- Receipt of a first cadaveric kidney graft
- Antilymphocyte antibodies and panel reactive antibodies (PRA) less than 30 percent (%) (historical peak and/or current value)
- Cold ischaemia time less than or equal to 36 hours
Exclusion Criteria
- Kidney from a living donor; donor greater than (>) 65 years of age; second renal graft, or more; or multiple organ transplant
- Known hypersensitivity to any of the drugs in the study or their components
- History of cancer or malignancy during previous 5 years, other than successfully treated spinocellular or basal cell cancer
- Participant presenting, on inclusion, either symptoms suggestive of active gastroduodenal ulcer, or gastroduodenal ulcer confirmed by fibroscopy and biopsy, and requiring treatment
- Participant with severe refractory hyperlipidaemia
- Pregnant woman or nursing mother
Exclusion Criteria for Follow-up Phase:
- Episode of acute rejection greater than or equal to grade I (Banff classification)
- Estimated creatinine clearance (CrCl) at week 12 less than (<) 40 milliliter per minute (mL/min) (Cockcroft-Gault formula)
- Serum creatinine variations >30% during the 15 days before randomization
- Proteinuria >1 gram/24 hour, or mean mycophenolate mofetil dose < 1.5 gram/day during the week before randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mycophenolate Mofetil + Cyclosporine Mycophenoate Mofetil Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. Mycophenolate Mofetil + Sirolimus Mycophenoate Mofetil Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. Mycophenolate Mofetil + Cyclosporine Cyclosporine Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. Mycophenolate Mofetil + Cyclosporine Daclizumab Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. Mycophenolate Mofetil + Sirolimus Cyclosporine Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. Mycophenolate Mofetil + Cyclosporine Prednisolone Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. Mycophenolate Mofetil + Sirolimus Daclizumab Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. Mycophenolate Mofetil + Sirolimus Prednisolone Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. Mycophenolate Mofetil + Sirolimus Sirolimus Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to approximately 12 months Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Week 52 52 weeks Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60 60 months Number of Participants With Serious Adverse Events (SAEs) From 12 months up to 60 months Number of Participants With Cancers and Lymphoproliferative Syndromes Up to approximately 12 months Number of Participants With Premature Discontinuations due to Adverse Events (AEs) Up to approximately 12 months Change From Baseline in 24-Hour Urinary Protein at Week 52 52 weeks
- Secondary Outcome Measures
Name Time Method Mean Inverse Creatinine Concentration Week 4, 8, 12, 14, 16, 26, 39, and 52 Number of Participants With Biopsy-proven Acute Rejections Baseline up to Month 60 Mean Serum Creatinine Concentration Week 4, 8, 12, 14, 16, 26, 39, and 52 Number of Participants With Histologic Evaluation of the Graft Week 52 Number of Participants Who Were Alive Month 60 Creatinine Clearance Calculated and Corrected According to Cockcroft-Gault Week 4, 8, 12, 14, 16, 26, 39, and 52 Number of Participants with Response to Treatment, Defined as Creatinine Clearance >/=60 mL/min at Week 52 Week 52 Glomerular Filtration Rate (GFR) Measured by Iohexol Clearance Baseline, Week 52 Number of Participants With Treated Rejections Baseline up to Week 52 Number of Participants With Graft Survival Month 60