Renal Transplantation
Conditions
Keywords
Renal, Allograft, Recipients
Brief summary
The purpose of this study is to determine the effect of conversion from calcineurin inhibitor to sirolimus based therapy on renal function.
Interventions
DRUGSirolimus
Sirolimus, Cyclosporine A & Tacrolimus are concentration controlled
DRUGtacrolimus
DRUGCyclosporine A
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than or equal to 13 years. * Receiving CsA or tacrolimus from the time of transplantation or within 2 weeks thereafter * Patients with a functioning allograft and a Nankivell GFR greater than or equal to 20 mL/min, within 2 weeks before randomization
Exclusion criteria
* Biopsy-confirmed acute rejection within 12 weeks before randomization, that was determined to require antirejection treatment * Patients in whom kidney-pancreas or other multiple organ transplants have been performed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nankivell Glomerular Filtration Rate (GFR) | 52 weeks | Nankivell GFR: patients with baseline GFR of 20.0 to 40.0 mL/min and patients with baseline GFR of greater than 40.0 mL/min. GFR is an index of kidney function. A higher value means better kidney function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 and 104 weeks | Number of patients who experienced for the first time either biopsy-confirmed acute rejection, graft loss, or death by weeks 52 and 104. Assessed by individual endpoint and as composite endpoint (all combined). |
Participant flow
Recruitment details
Patients were recruited worldwide from January 2002 to September 2003.
Pre-assignment details
Patients were screened for two weeks.
Participants by arm
| Arm | Count |
|---|---|
| SRL Conversion in Stable Renal Transplant Recipients Conversion from calcineurin inhibitor immunosuppression therapy to Sirolimus-based immunosuppression therapy. | 555 |
| CNI Continuation in Stable Renal Transplant Recipients Continued calcineurin inhibitor immunosuppression therapy | 275 |
| Total | 830 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 131 | 43 |
| Overall Study | Lack of Efficacy | 3 | 6 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Nonmedical event | 5 | 7 |
| Overall Study | Protocol Violation | 3 | 7 |
| Overall Study | Withdrawal by Subject | 23 | 10 |
Baseline characteristics
| Characteristic | SRL Conversion in Stable Renal Transplant Recipients | CNI Continuation in Stable Renal Transplant Recipients | Total |
|---|---|---|---|
| Age Continuous | 45.00 years | 43.50 years | 44.50 years |
| Sex: Female, Male Female | 170 Participants | 81 Participants | 251.0 Participants |
| Sex: Female, Male Male | 385 Participants | 194 Participants | 579.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 545 / 551 | 264 / 273 |
| serious Total, serious adverse events | 81 / 551 | 45 / 273 |
Outcome results
Primary
Nankivell Glomerular Filtration Rate (GFR)
Nankivell GFR: patients with baseline GFR of 20.0 to 40.0 mL/min and patients with baseline GFR of greater than 40.0 mL/min. GFR is an index of kidney function. A higher value means better kidney function.
Time frame: 52 weeks
Population: Patients were stratified by GFR at baseline. GFR 20-40 mL/min and GFR \>40 mL/min.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRL Conversion Strata 20.0-40.0 mL/Min | Nankivell Glomerular Filtration Rate (GFR) | 24.56 mL/min | Standard Error 2.42 |
| CNI Continuation Strata 20.0-40.0 mL/Min | Nankivell Glomerular Filtration Rate (GFR) | 27.24 mL/min | Standard Error 3.71 |
| SRL Conversion Strata >40.0 mL/Min | Nankivell Glomerular Filtration Rate (GFR) | 59.04 mL/min | Standard Error 0.89 |
| CNI Continuation Strata >40.0 mL/Min | Nankivell Glomerular Filtration Rate (GFR) | 57.73 mL/min | Standard Error 1.1 |
Comparison: Baseline GFR of \>40.0 mL/minp-value: 0.27895% CI: [-1.06, 3.69]ANCOVA
Comparison: Baseline GFR of 20.0 to 40.0 mL/minp-value: 0.57595% CI: [-12.27, 6.91]ANCOVA
Secondary
First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death.
Number of patients who experienced for the first time either biopsy-confirmed acute rejection, graft loss, or death by weeks 52 and 104. Assessed by individual endpoint and as composite endpoint (all combined).
Time frame: 52 and 104 weeks
Population: Patients were stratified by GFR at baseline. GFR 20-40 mL/min and GFR \>40 mL/min.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Graft loss | 7 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Death | 7 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Death | 3 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Acute rejection | 5 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Acute rejection | 4 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Missing | 0 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Graft loss | 12 patients |
| SRL Conversion Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Missing | 0 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Missing | 0 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Acute rejection | 0 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Graft loss | 3 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Death | 0 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Acute rejection | 1 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Graft loss | 9 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Death | 0 patients |
| CNI Continuation Strata 20.0-40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Missing | 2 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Acute rejection | 8 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Missing | 13 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Death | 13 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Acute rejection | 27 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Graft loss | 3 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Graft loss | 12 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Death | 6 patients |
| SRL Conversion Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Missing | 5 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Death | 1 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Acute rejection | 9 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Missing | 8 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Graft loss | 8 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Missing | 1 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Graft loss | 3 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 104 weeks - Death | 3 patients |
| CNI Continuation Strata >40.0 mL/Min | First Occurrence of Biopsy-confirmed Acute Rejection, Graft Loss, or Death. | 52 weeks - Acute rejection | 3 patients |
Comparison: 52 weeks statistical analysis across stratap-value: 0.135Cochran-Mantel-Haenszel
Comparison: 104 weeks statistical analysis across stratap-value: 0.559Cochran-Mantel-Haenszel