Kidney Transplantation
Conditions
Keywords
Renal, Kidney, Intensified, Enteric-coated mycophenolate sodium, Transplant
Brief summary
The purpose of this study is to determine if an initial intensified enteric-coated mycophenolate sodium (Myfortic) dosing regimen administered during the first six weeks post renal transplantation provides improved efficacy, with a similar safety profile, compared to a standard regimen of Myfortic.
Interventions
DRUGEnteric-coated mycophenolate sodium (Myfortic)
1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.
cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels
DRUGPrednisone
20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Inclusion criteria
* Males or females, 18 to 65 years old * First or second time kidney transplant patients * For females capable of becoming pregnant, negative pregnancy test prior to entry into trial and effective birth control during trial and 3 months after stopping trial medication
Exclusion criteria
* Previous graft loss due to immunological reasons in the 1st year after the 1st transplant * Multi-organ recipients or previous transplant of another organ, different from the kidney * Recipients from a non-heart-beating donor * Known hypersensitivity to mycophenolic acid or cyclosporine * HIV positive or Hepatitis B surface antigen positive * History of malignancy (past 5 years) * Pregnancy or planned pregnancy, lactating, or unwillingness to use effective contraception. * Evidence of severe liver disease Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death | 6 months | To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection \[BPAR\], graft loss \[GFL\] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Function Assessed by Serum Creatinine at Each Visits | at 21 days, 84 days and 180 days | — |
| Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | 21 and 84 days | The overall treatment differences of the number of participants with at least one occurrence of the composite event BPAR, GFL or death at study days 21 and 84 post-transplantation. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.) |
| Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | at 21 days, 84 days and 180 days | The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the GFR. Serum creatinine levels, age, sex and race were used to estimate the GFR levels in mL/min/1.73m\^2. |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen In patients randomized to the intensified Myfortic dosing regimen, the initial dose was 2-fold of the labeled dose (i.e. 2880 mg/day). The dosage was reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment. | 155 |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen In patients randomized to the standard Myfortic dosing regimen, the initial dose of 1440mg/day had to be maintained throughout the whole study. | 158 |
| Total | 313 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Problem | 4 | 4 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Total |
|---|---|---|---|
| Age, Customized < 50 years | 100 participants | 102 participants | 202 participants |
| Age, Customized >=50 years | 55 participants | 56 participants | 111 participants |
| Sex: Female, Male Female | 53 Participants | 54 Participants | 107 Participants |
| Sex: Female, Male Male | 102 Participants | 104 Participants | 206 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 143 / 150 | 145 / 154 |
| serious Total, serious adverse events | 74 / 150 | 68 / 154 |
Outcome results
Primary
Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death
To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection \[BPAR\], graft loss \[GFL\] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)
Time frame: 6 months
Population: Intention to treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death | 33 number of participants |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death | 36 number of participants |
Primary
Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death
To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection \[BPAR\], graft loss \[GFL\] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)
Time frame: 6 months
Population: Per Protocol (PP) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death | 26 number of participants |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death | 35 number of participants |
Secondary
Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death
The overall treatment differences of the number of participants with at least one occurrence of the composite event BPAR, GFL or death at study days 21 and 84 post-transplantation. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)
Time frame: 21 and 84 days
Population: Intention to treat (ITT) population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 21 | 20 number of participants |
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 84 | 33 number of participants |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 21 | 21 number of participants |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 84 | 34 number of participants |
Secondary
Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death
The overall treatment differences of the number of participants with at least one occurrence of the composite event BPAR, GFL or death at study days 21 and 84 post-transplantation. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)
Time frame: 21 and 84 days
Population: Per Protocol (PP) population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 21 | 14 number of participants |
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 84 | 26 number of participants |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 21 | 20 number of participants |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death | Day 84 | 33 number of participants |
Secondary
Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit
The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the GFR. Serum creatinine levels, age, sex and race were used to estimate the GFR levels in mL/min/1.73m\^2.
Time frame: at 21 days, 84 days and 180 days
Population: Intention to treat (ITT) population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | At 21 days | 47.3 (mL/min/1.73m^2) | Standard Deviation 20.05 |
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | At 84 days | 52.1 (mL/min/1.73m^2) | Standard Deviation 19.8 |
| Intensified Mycophenolate Sodium (Myfortic) Dosing Regimen | Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | At 180 days | 53.5 (mL/min/1.73m^2) | Standard Deviation 21.05 |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | At 21 days | 46.8 (mL/min/1.73m^2) | Standard Deviation 21 |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | At 84 days | 51.8 (mL/min/1.73m^2) | Standard Deviation 20.21 |
| Standard Mycophenolate Sodium (Myfortic) Dosing Regimen | Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit | At 180 days | 51.3 (mL/min/1.73m^2) | Standard Deviation 25.14 |
Secondary
Renal Function Assessed by Serum Creatinine at Each Visits
Time frame: at 21 days, 84 days and 180 days