Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

A Randomized, Open-label, Comparative Evaluation of Conversion From Calcineurin Inhibitors to Sirolimus Versus Continued Use of Calcineurin Inhibitors in Renal Allograft Recipient

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).

Study Overview

• Status: Terminated
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Sirolimus+MMF or MPS or AZA+Steroid; Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid

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 Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Select Cities, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; 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.
ACTIVE_COMPARATOR: 2; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Change From Baseline in Diastolic Blood Pressure at Week 24	Value at Week 24 minus value at baseline.	Baseline and Week 24
Change From Baseline in Diastolic Blood Pressure at Week 52	Value at Week 52 minus value at baseline.	Baseline and Week 52
Change From Baseline in Diastolic Blood Pressure at Week 104	Value at Week 104 minus value at baseline.	Baseline and Week 104
Change From Baseline in Systolic Blood Pressure at Week 24	Value at Week 24 minus value at baseline.	Baseline and Week 24
Change From Baseline in Systolic Blood Pressure at Week 52	Value at Week 52 minus value at baseline.	Baseline and Week 52
Change From Baseline in Systolic Blood Pressure at Week 104	Value at Week 104 minus value at baseline.	Baseline and Week 104
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

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): August 1, 2008

Study Registration Dates

• First Submitted: March 23, 2007
• First Submitted That Met QC Criteria: March 26, 2007
• First Posted (ESTIMATE): March 27, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): September 3, 2012
• Last Update Submitted That Met QC Criteria: July 27, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Tacrolimus; Sirolimus; Cyclosporine; Cyclosporins; Calcineurin Inhibitors
• Other Study ID Numbers: 0468H-101864