Conditions: Kidney Transplantation
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 31
Healthy volunteers: no

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.

Arms:
arm 1: Sirolimus therapy arm 2: Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus)

Interventions: intervention 1: Sirolimus+MMF or MPS or AZA+Steroid intervention 2: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid
Intervention descriptions: intervention 1: Corticosteroids will be administered according to local practice, within a daily maintenance dosage range of 2.5 to15 mg for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent. intervention 2: The maintenance dose of:

1. MMF will not exceed 1500 mg/day or PMS will not exceed 1080 mg/day
2. AZA will not exceed 75 mg/day

Thereafter, at the discretion of the investigator, MMF/MPS or AZA may be:

1. continued for the entire 104-week period of randomized therapy
2. subsequently discontinued
3. restarted after discontinuation

Protocol document: