Kidney Transplantation
Conditions
Brief summary
This observational study will evaluate renal function in participants who underwent renal allograft transplantation and are started on combined immunosuppressive treatment containing mycophenolate mofetil (CellCept). Eligible participants will be followed for 12 months following transplantation.
Detailed description
The participant sampling method used in the Orange study was consecutive sampling, a non-probability sampling method where each participant meeting the study's inclusion and exclusion criteria is selected and enrolled in the study until the pre-set sample size is achieved. Thus, in the Orange study de novo kidney transplanted participants, who were on mycophenolate mofetil immunosuppressive combination therapy in routine clinical practice, were selected in a consecutive manner (a non-probability sampling method) if they met the inclusion/exclusion criteria until 128 participants were recruited to the study.
Interventions
DRUGMycophenolate Mofetil
Protocol does not specify any regimen for treatment. The choice of treatment will be made prior to enrollment by the treating physician.
Protocol does not specify any particular immunosuppressive drug and regimen for treatment. The choice of immunosuppressive therapy will be made prior to enrollment by the treating physician.
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who underwent renal allograft transplantation and are started on combined immunosuppressive treatment containing mycophenolate mofetil in accordance with the indication provided by the SmPC of mycophenolate mofetil * Date of study enrollment is the date of kidney transplantation
Exclusion criteria
* Contraindication included in the SmPC for capecitabine (Xeloda) prevailed, like: Hypersensitivity to active ingredient or any of the excipients of the product; Pregnancy and lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GFR at Month 12 After Transplantation | Month 12 | GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is \> 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR \< 15 mL/min indicates kidney failure. |
| Creatinine Clearance at Month 6 After Transplantation | Month 6 | Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function. |
| Creatinine Clearance at Month 12 After Transplantation | Month 12 | Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function. |
| Glomerular Filtration Rate (GFR) at Month 1 After Transplantation | Month 1 | GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is greater than (\>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR less than (\<) 15 mL/min indicates kidney failure. |
| GFR at Month 6 After Transplantation | Month 6 | GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is \> 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR \< 15 mL/min indicates kidney failure. |
| Creatinine Clearance at 1 Month After Transplantation | Month 1 | Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | Baseline, Months 1, 6, and 12 | Participants could have received more than one other immunosuppressive agents, at the discretion of treating physician. Percentage of participants who received 1 other immunosuppressive agent, 2 other immunosuppressive agents, and 3 other immunosuppressive agents are reported. |
| Percentage of Participants With Acute Rejection | Baseline to Month 1, Months 2 to 6, Months 7 to 12 | Percentage of participants who experienced acute rejection within 1 month of transplantation, Month 2 to Month 6 after transplantation, Month 7 to Month 12 after transplantation are reported. |
| Percentage of Participants With Graft Survival | Months 1, 6, and 12 | Graft survival was 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), re-transplant or death during the first 12 months after transplantation. |
| Mean Dose of Mycophenolate Mofetil | Baseline, Months 1, 6, and 12 | — |
Countries
Hungary
Participant flow
Pre-assignment details
If Informed Consent Form (ICF) was signed after the transplantation, it was considered as a major protocol violation and reported separately from protocol violation in Participant Flow.
Participants by arm
| Arm | Count |
|---|---|
| Renal Transplant Participants Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen. | 123 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | ICF Signed After Transplantation | 5 |
| Overall Study | Protocol Violation | 48 |
Baseline characteristics
| Characteristic | Renal Transplant Participants |
|---|---|
| Age, Continuous | 49.60 years STANDARD_DEVIATION 13.24 |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 128 |
| serious Total, serious adverse events | 33 / 128 |
Outcome results
Primary
Creatinine Clearance at 1 Month After Transplantation
Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time frame: Month 1
Population: ITT population. Number of participants analyzed = participants evaluable for creatinine clearance at specified time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Transplant Participants | Creatinine Clearance at 1 Month After Transplantation | 65.82 mL/min | Standard Deviation 18.32 |
Primary
Creatinine Clearance at Month 12 After Transplantation
Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time frame: Month 12
Population: ITT population. Number of participants analyzed = participants evaluable for creatinine clearance at specified time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Transplant Participants | Creatinine Clearance at Month 12 After Transplantation | 69.69 mL/min | Standard Deviation 21.05 |
Primary
Creatinine Clearance at Month 6 After Transplantation
Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time frame: Month 6
Population: ITT population. Number of participants analyzed = participants evaluable for creatinine clearance at specified time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Transplant Participants | Creatinine Clearance at Month 6 After Transplantation | 73.38 mL/min | Standard Deviation 19.43 |
Primary
GFR at Month 12 After Transplantation
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is \> 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR \< 15 mL/min indicates kidney failure.
Time frame: Month 12
Population: ITT population. Number of participants analyzed = participants evaluable for GFR at specified time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Transplant Participants | GFR at Month 12 After Transplantation | 58.03 mL/min | Standard Deviation 16.29 |
Primary
GFR at Month 6 After Transplantation
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is \> 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR \< 15 mL/min indicates kidney failure.
Time frame: Month 6
Population: ITT population. Number of participants analyzed = participants evaluable for GFR at specified time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Transplant Participants | GFR at Month 6 After Transplantation | 56.78 mL/min | Standard Deviation 15.36 |
Primary
Glomerular Filtration Rate (GFR) at Month 1 After Transplantation
GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is greater than (\>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR less than (\<) 15 mL/min indicates kidney failure.
Time frame: Month 1
Population: ITT population. Number of participants analyzed = participants evaluable for GFR at specified time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Transplant Participants | Glomerular Filtration Rate (GFR) at Month 1 After Transplantation | 53.54 mL/min | Standard Deviation 33.43 |
Secondary
Mean Dose of Mycophenolate Mofetil
Time frame: Baseline, Months 1, 6, and 12
Population: ITT population. Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Transplant Participants | Mean Dose of Mycophenolate Mofetil | Baseline (n=121) | 2033.06 milligrams (mg) | Standard Deviation 357.86 |
| Renal Transplant Participants | Mean Dose of Mycophenolate Mofetil | Month 1 (n=119) | 1718.49 milligrams (mg) | Standard Deviation 543.21 |
| Renal Transplant Participants | Mean Dose of Mycophenolate Mofetil | Month 6 (n=88) | 1457.39 milligrams (mg) | Standard Deviation 754.51 |
| Renal Transplant Participants | Mean Dose of Mycophenolate Mofetil | Month 12 (n=69) | 1539.86 milligrams (mg) | Standard Deviation 669.21 |
Secondary
Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil
Participants could have received more than one other immunosuppressive agents, at the discretion of treating physician. Percentage of participants who received 1 other immunosuppressive agent, 2 other immunosuppressive agents, and 3 other immunosuppressive agents are reported.
Time frame: Baseline, Months 1, 6, and 12
Population: ITT population. Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 1 Other agent: at baseline (n=121) | 0.8 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 1 Other agent: at Month 1 (n=119) | 0.8 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 1 Other agent: at Month 6 (n=86) | 2.3 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 1 Other agent: at Month 12 (n=69) | 7.2 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 2 Other agents: at baseline (n=121) | 90.9 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 2 Other agents: at Month 1 (n=119) | 99.2 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 2 Other agents: at Month 6 (n=86) | 97.7 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 2 Other agents: at Month 12 (n=69) | 92.8 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 3 Other agents: at baseline (n=121) | 8.3 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 3 Other agents: at Month 1 (n=119) | 0 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 3 Other agents: at Month 6 (n=86) | 0 percentage of participants |
| Renal Transplant Participants | Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil | 3 Other agents: at Month 12 (n=69) | 0 percentage of participants |
Secondary
Percentage of Participants With Acute Rejection
Percentage of participants who experienced acute rejection within 1 month of transplantation, Month 2 to Month 6 after transplantation, Month 7 to Month 12 after transplantation are reported.
Time frame: Baseline to Month 1, Months 2 to 6, Months 7 to 12
Population: Safety population included all enrolled renal transplant participants who received mycophenolate mofetil containing immunosuppressive combination therapy (safety population=128). Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Renal Transplant Participants | Percentage of Participants With Acute Rejection | Baseline to Month 1 (n=127) | 16.5 percentage of participants |
| Renal Transplant Participants | Percentage of Participants With Acute Rejection | Months 2 to 6 (n=124) | 0.8 percentage of participants |
| Renal Transplant Participants | Percentage of Participants With Acute Rejection | Months 7 to 12 (n=111) | 0.9 percentage of participants |
Secondary
Percentage of Participants With Graft Survival
Graft survival was 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), re-transplant or death during the first 12 months after transplantation.
Time frame: Months 1, 6, and 12
Population: Safety population. Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Renal Transplant Participants | Percentage of Participants With Graft Survival | Month 1 (n=127) | 100 percentage of participants |
| Renal Transplant Participants | Percentage of Participants With Graft Survival | Month 6 (n=123) | 99.2 percentage of participants |
| Renal Transplant Participants | Percentage of Participants With Graft Survival | Month 12 (n=111) | 98.4 percentage of participants |