Renal Transplant
Conditions
Brief summary
Primary : To evaluate the efficacy of sirolimus assessed by the incidence of biopsy-confirmed acute rejection episode at 6 months after transplantation in Korean renal transplantation recipients. Secondary : 1. To evaluate the safety of sirolimus over 12 months after transplantation in Korean renal transplantation recipients. 2. To evaluate graft function, patient survival and graft survival at 6 and 12 months after transplantation, and to investigate the incidence of biopsy-confirmed acute rejection episode at 12 months after transplantation.
Interventions
(1mg tablets): Initial loading dose of 6mg/day, followed by maintenance dose of 2mg/day, which was adjusted to specified trough level.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than or equal to 13 years of age. 2. End-stage renal disease in patients scheduled to receive a primary renal allograft from a cadaveric donor, a living-unrelated donor, or from a living-related (excluding 0 antigen mismatch) donor. A mismatch donor is defined as a donor human leukocyte antigen (HLA) antigen not shared by the patient. 3. Patients with a panel of reactive antibody (%PRA) less than or equal to 50%
Exclusion criteria
1. Evidence of active systemic or localized major infection at the time of initial sirolimus administration. 2. Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening. 3. Chronic anti-arrhythmic therapy for ventricular arrhythmia or other cardiac abnormality contraindicating general anesthesia or surgery. 4. History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin). 5. Current treatment with partial opioid agonists (eg, buprenorphine) or combination agonists/antagonists.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 6 After Transplantation. | 6 months after transplantation | The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glomerular Filtration Rate (GFR) (Nankivell Method) | 6 and 12 months | 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. For this study, GFR was calculated using the Nankivell formula. A normal GFR is \>90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poorer kidney function. A GFR \<15 is consistent with kidney failure. |
| Serum Creatinine | Baseline, 6 and 12 months | Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass. |
| Patient and Graft Survival | 12 months | Patient survival defined as patients living with or without a functioning graft. Graft survival defined as those patients 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. |
| Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 12 After Transplantation | 12 months after transplantation | The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions). |
Countries
South Korea
Participant flow
Recruitment details
Patients were recruited in Korea from March 2007 to November 2007.
Pre-assignment details
Patients were screened up to 7 days.
Participants by arm
| Arm | Count |
|---|---|
| Sirolimus (SRL) Patients initially received SRL, Cyclosporine (CsA) and Corticosteroids. After 2-4 months following transplantation, CsA was progressively withdrawn.
On Day 1 (within 48 hours after transplantation) SRL was initiated (6 mg loading dose). For Day 2 through CsA withdrawal (w/d), SRL dose was 2mg/day, with adjustment to maintain a target trough blood level of 5-15 ng/ml. During CsA w/d through month 6, SRL dose adjusted to a trough level of 15-30 ng/ml; and for months 7-12, a trough level of 12-24 ng/ml.
CsA initiated before or within 48 hours after transplantation at a dose to attain a trough level of 200-400 ng/ml. From month 1 to time of CsA w/d, CsA dose was adjusted to maintain a trough level of 150-300 ng/ml. At 2 to 4 months after transplantation, CsA was withdrawn over 4-8 weeks.
Corticosteroids were initiated within 24 hours before or after transplantation and tapered to ≥ 5 mg/day of prednisone by the end of week 13. W/d of corticosteroids was prohibited. | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Serious Adverse Event | 14 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Sirolimus (SRL) |
|---|---|
| Age Continuous | 40.16 years STANDARD_DEVIATION 12.69 |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 79 / 79 |
| serious Total, serious adverse events | 39 / 79 |
Outcome results
Primary
Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 6 After Transplantation.
The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).
Time frame: 6 months after transplantation
Population: Patients who received at least one dosing of SRL after transplantation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirolimus (SRL) | Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 6 After Transplantation. | 12 patients |
Secondary
Glomerular Filtration Rate (GFR) (Nankivell Method)
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. For this study, GFR was calculated using the Nankivell formula. A normal GFR is \>90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poorer kidney function. A GFR \<15 is consistent with kidney failure.
Time frame: 6 and 12 months
Population: Patients who received at least one dose of SRL after transplantation. Observed values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sirolimus (SRL) | Glomerular Filtration Rate (GFR) (Nankivell Method) | 6 months | 67.36 mL/min | Standard Deviation 15.25 |
| Sirolimus (SRL) | Glomerular Filtration Rate (GFR) (Nankivell Method) | 12 months | 71.92 mL/min | Standard Deviation 18.82 |
Secondary
Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 12 After Transplantation
The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).
Time frame: 12 months after transplantation
Population: Patients who received at least one dosing of SRL after transplantation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirolimus (SRL) | Number of Patients Experiencing Biopsy Confirmed Acute Rejection Through Month 12 After Transplantation | 15 patients |
Secondary
Patient and Graft Survival
Patient survival defined as patients living with or without a functioning graft. Graft survival defined as those patients 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.
Time frame: 12 months
Population: Patients who received at least one dosing of SRL after transplantation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirolimus (SRL) | Patient and Graft Survival | Patient survival 12 months | 76 patients |
| Sirolimus (SRL) | Patient and Graft Survival | Patient survival 6 months | 77 patients |
| Sirolimus (SRL) | Patient and Graft Survival | Graft survival 6 months | 77 patients |
| Sirolimus (SRL) | Patient and Graft Survival | Graft survival 12 months | 76 patients |
Secondary
Serum Creatinine
Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.
Time frame: Baseline, 6 and 12 months
Population: Patients who received at least one dose of SRL after transplantation. Observed values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sirolimus (SRL) | Serum Creatinine | Baseline | 9.42 mg/dl | Standard Deviation 3.64 |
| Sirolimus (SRL) | Serum Creatinine | 6 months | 1.30 mg/dl | Standard Deviation 0.36 |
| Sirolimus (SRL) | Serum Creatinine | 12 months | 1.25 mg/dl | Standard Deviation 0.43 |