Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

Kidney Transplantation Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00452361
• Other study ID #: 0468H-101864
• Status: Terminated
• Phase: Phase 4
• First received: March 23, 2007
• Last updated: July 27, 2012
• Start date: April 2007
• Est. completion date: August 2008

Study information

• Verified date: July 2012
• Source: Wyeth is now a wholly owned subsidiary of Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

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.
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glomerular Filtration Rate (GFR) Change From Baseline	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.	104 weeks	No
Secondary	Change in Glomerular Filtration Rate (GFR)	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.	Baseline and Week 24	No
Secondary	Change in Glomerular Filtration Rate (GFR)	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.	Baseline and Week 52	No
Secondary	Change in Glomerular Filtration Rate (GFR)	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.	Baseline and Week 104	No
Secondary	Patient and Graft Survival	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.	Week 24	Yes
Secondary	Patient and Graft Survival	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.	Week 52	Yes
Secondary	Patient and Graft Survival	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.	Week 104	Yes
Secondary	Change From Baseline in Diastolic Blood Pressure at Week 24	Value at Week 24 minus value at baseline.	Baseline and Week 24	No
Secondary	Change From Baseline in Diastolic Blood Pressure at Week 52	Value at Week 52 minus value at baseline.	Baseline and Week 52	No
Secondary	Change From Baseline in Diastolic Blood Pressure at Week 104	Value at Week 104 minus value at baseline.	Baseline and Week 104	No
Secondary	Change From Baseline in Systolic Blood Pressure at Week 24	Value at Week 24 minus value at baseline.	Baseline and Week 24	No
Secondary	Change From Baseline in Systolic Blood Pressure at Week 52	Value at Week 52 minus value at baseline.	Baseline and Week 52	No
Secondary	Change From Baseline in Systolic Blood Pressure at Week 104	Value at Week 104 minus value at baseline.	Baseline and Week 104	No
Secondary	Change From Baseline in the Severity and Progression of Biopsy-Confirmed Chronic Allograft Nephropathy (CAN) at Week 104		Baseline and Week 104	No
Secondary	Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52		Weeks 52	No
Secondary	Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104		Week 104	No
Secondary	Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24		Week 24	No
Secondary	Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52		Week 52	No
Secondary	Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104		Week 104	No