Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00452361
First received: March 23, 2007
Last updated: July 27, 2012
Last verified: July 2012
  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 4

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


Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:

Primary Outcome Measures:
  • Change in Glomerular Filtration Rate (GFR) Change From Baseline [ Time Frame: 104 weeks ] [ Designated as safety issue: No ]
    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:
  • Change in Glomerular Filtration Rate (GFR) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change in Glomerular Filtration Rate (GFR) [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    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.

  • Change in Glomerular Filtration Rate (GFR) [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    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.

  • Patient and Graft Survival [ Time Frame: Week 52 ] [ Designated as safety issue: Yes ]
    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.

  • Patient and Graft Survival [ Time Frame: Week 104 ] [ Designated as safety issue: Yes ]
    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 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Value at Week 24 minus value at baseline.

  • Change From Baseline in Diastolic Blood Pressure at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Value at Week 52 minus value at baseline.

  • Change From Baseline in Diastolic Blood Pressure at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
    Value at Week 104 minus value at baseline.

  • Change From Baseline in Systolic Blood Pressure at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Value at Week 24 minus value at baseline.

  • Change From Baseline in Systolic Blood Pressure at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Value at Week 52 minus value at baseline.

  • Change From Baseline in Systolic Blood Pressure at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52 [ Time Frame: Weeks 52 ] [ Designated as safety issue: No ]
  • Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  • Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  • Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: April 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:

  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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Taiwan
Select Cities, Taiwan
Sponsors and Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Study Director: Medical Monitor Wyeth is now a wholly owned subsidiary of Pfizer
  More Information

No publications provided

Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier: NCT00452361     History of Changes
Other Study ID Numbers: 0468H-101864
Study First Received: March 23, 2007
Results First Received: September 24, 2009
Last Updated: July 27, 2012
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Sirolimus
Everolimus
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 28, 2014