Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient - Full Text View

Sponsored by:	Wyeth
Information provided by:	Wyeth
ClinicalTrials.gov Identifier:	NCT00452361

Purpose

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).

Condition	Intervention	Phase
Kidney Transplantation	Drug: Sirolimus+MMF or MPS or AZA+Steroid Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Open-label, Comparative Evaluation of Conversion From Calcineurin Inhibitors to Sirolimus Versus Continued Use of Calcineurin Inhibitors in Renal Allograft Recipient

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Sirolimus Cyclosporine Tacrolimus

U.S. FDA Resources

Further study details as provided by Wyeth:

Primary Outcome Measures:

To determine the effect of conversion from CI- to SRL based therapy on renal function 104 weeks after randomization, as indicated by the change from baseline Nankivell GFR. [ Time Frame: 104 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence and severity of rejection at 24, 52, 104 weeks; GFR at 24, 52, 104 weeks; patient and graft survival at 24, 52 and 104 weeks; blood presure at 24, 52, 104 weeks; severity and progression of biopsy-confirmed CAN at 104 weeks. To assess safety. [ Time Frame: 24, 52, 104 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	120
Study Start Date:	April 2007
Study Completion Date:	September 2008
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Sirolimus therapy	Drug: Sirolimus+MMF or MPS or AZA+Steroid 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.
2: Active Comparator Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus)	Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid The maintenance dose of: MMF will not exceed 1500 mg/day or PMS will not exceed 1080 mg/day AZA will not exceed 75 mg/day Thereafter, at the discretion of the investigator, MMF/MPS or AZA may be: continued for the entire 104-week period of randomized therapy subsequently discontinued restarted after discontinuation

Arms

Assigned Interventions

1: Experimental

Sirolimus therapy

Drug: Sirolimus+MMF or MPS or AZA+Steroid

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.

2: Active Comparator

Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus)

Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid

The maintenance dose of:

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

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

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00452361

Locations

Taiwan

Select Cities, Taiwan

Sponsors and Collaborators

Wyeth

Investigators

Study Director:

Medical Monitor

Wyeth

More Information

No publications provided

Responsible Party:	Wyeth ( Wyeth (Registry Contact: Clinical Trial Registry Specialist) )
Study ID Numbers:	0468H-101864
Study First Received:	March 23, 2007
Last Updated:	July 31, 2009
ClinicalTrials.gov Identifier:	NCT00452361 History of Changes
Health Authority:	Taiwan: Department of Health

Study placed in the following topic categories:

Sirolimus
Prednisone
Anti-Infective Agents
Cyclosporine
Immunologic Factors
Methylprednisolone
Methylprednisolone acetate
Prednisolone acetate

Tacrolimus
Immunosuppressive Agents
Cyclosporins
Anti-Bacterial Agents
Antifungal Agents
Prednisolone
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:

Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Antifungal Agents

Therapeutic Uses
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 10, 2009