Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

• Change in Glomerular Filtration Rate (GFR) Change From Baseline [ Time Frame: 104 weeks ]
  GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
  
  

• Change in Glomerular Filtration Rate (GFR) [ Time Frame: Baseline and Week 24 ]
  GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
  
  
• Change in Glomerular Filtration Rate (GFR) [ Time Frame: Baseline and Week 52 ]
  GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
  
  
• Change in Glomerular Filtration Rate (GFR) [ Time Frame: Baseline and Week 104 ]
  GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using Nankivell formula. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
  
  
• Patient and Graft Survival [ Time Frame: Week 24 ]
  Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
  
  
• Patient and Graft Survival [ Time Frame: Week 52 ]
  Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
  
  
• Patient and Graft Survival [ Time Frame: Week 104 ]
  Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
  
  
• Change From Baseline in Diastolic Blood Pressure at Week 24 [ Time Frame: Baseline and Week 24 ]
  Value at Week 24 minus value at baseline.
  
  
• Change From Baseline in Diastolic Blood Pressure at Week 52 [ Time Frame: Baseline and Week 52 ]
  Value at Week 52 minus value at baseline.
  
  
• Change From Baseline in Diastolic Blood Pressure at Week 104 [ Time Frame: Baseline and Week 104 ]
  Value at Week 104 minus value at baseline.
  
  
• Change From Baseline in Systolic Blood Pressure at Week 24 [ Time Frame: Baseline and Week 24 ]
  Value at Week 24 minus value at baseline.
  
  
• Change From Baseline in Systolic Blood Pressure at Week 52 [ Time Frame: Baseline and Week 52 ]
  Value at Week 52 minus value at baseline.
  
  
• Change From Baseline in Systolic Blood Pressure at Week 104 [ Time Frame: Baseline and Week 104 ]
  Value at Week 104 minus value at baseline.
  
  
• Change From Baseline in the Severity and Progression of Biopsy-Confirmed Chronic Allograft Nephropathy (CAN) at Week 104 [ Time Frame: Baseline and Week 104 ]
  
• Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52 [ Time Frame: Weeks 52 ]
  
• Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104 [ Time Frame: Week 104 ]
  
• Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24 [ Time Frame: Week 24 ]
  
• Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52 [ Time Frame: Week 52 ]
  
• Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104 [ Time Frame: Week 104 ]
  

This open-label, randomized, parallel-group, comparative, outpatient study will be conducted in multiple centers in Taiwan.

The study will randomize approximately 120 patients. 80 patients will be randomized to the SRL therapy group (conversion from CI- to SRL-based immunosuppression: group A) and 40 patients to the CI therapy group (continued CI therapy: group B).

Dosage and Administration

SRL Therapy: At the time of randomization on day 1, each patient will have been receiving:

• triple therapy with a CI (tacrolimus or CsA) that began at the time of transplantation or within 2 weeks thereafter AND
• corticosteroids corresponding to a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent for at least 12 weeks before randomization, PLUS
• either MMF (minimum dose 500 mg/day)/MPS (minimum dose 360 mg/day) or AZA (minimum dose 50 mg/day) for at least 12 weeks before randomization.

SRL will be added to the immunosuppressive regimen for Group A. Group B will continue on this CI immunosuppressive regimen.