Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

Phase 4

Terminated

• Conditions: Kidney Transplantation
• Interventions: Drug: Sirolimus+MMF or MPS or AZA+Steroid; Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid

• Registration Number: NCT00452361
• Lead Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

Brief Summary

This study will evaluate whether conversion from cyclosporine, a calcineurin inhibitor (CI) to sirolimus (SRL) results in improved long-term renal function without a negative impact on safety or immunosuppressive efficacy, and to further examine the potential of SRL to reduce the severity and/or progression of chronic allograft nephropathy (CAN).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2007-03-23
• Study First Submitted QC: 2007-03-26
• Study First Posted: 2007-03-27
• Study Start: 2007-04
• Primary Completion: 2008-08
• Study Completion: 2008-08
• Results First Submitted: 2009-09-24
• Status Verified: 2012-07
• Results First Submitted QC: 2012-07-27
• Last Update Submitted: 2012-07-27
• Results First Posted: 2012-09-03
• Last Update Posted: 2012-09-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

• Subjects must be at least 18 years of age.
• Subjects who are 6 to 60 months after renal transplantation.
• Subjects who have a stable graft function.

Exclusion Criteria

• Subjects with active major infection, including HIV, decreased platelets, elevated lipids, or multiple organ transplants.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Sirolimus+MMF or MPS or AZA+Steroid	Sirolimus therapy
2	Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid	Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus)

Primary Outcome Measures

Name	Time	Method
Change in Glomerular Filtration Rate (GFR) Change From Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Diastolic Blood Pressure at Week 24	Baseline and Week 24	Value at Week 24 minus value at baseline.
Change From Baseline in Systolic Blood Pressure at Week 24	Baseline and Week 24	Value at Week 24 minus value at baseline.
Change From Baseline in Systolic Blood Pressure at Week 52	Baseline and Week 52	Value at Week 52 minus value at baseline.
Change in Glomerular Filtration Rate (GFR)	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	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 52	Baseline and Week 52	Value at Week 52 minus value at baseline.
Change From Baseline in Diastolic Blood Pressure at Week 104	Baseline and Week 104	Value at Week 104 minus value at baseline.
Change From Baseline in Systolic Blood Pressure at Week 104	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	Baseline and Week 104
Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52	Weeks 52
Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104	Week 104
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24	Week 24
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52	Week 52
Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104	Week 104