Renal Transplant
Conditions
Keywords
Renal transplant, everolimus, cardiovascular profile, CNI-free immunosuppression, left ventricular hypertrophy, biopsy proved acute rejection (BPAR)
Brief summary
The objective of the study is to compare the cardiovascular profile of an everolimus and mycophenolic acid immunosuppressive regimen with a calcineurin inhibitor and mycophenolic acid regimen in maintenance renal transplant patients
Interventions
DRUGEverolimus
Everolimus was supplied in boxes with 60 tablets. Available tablets: 1.0 mg, 0.5 mg and 0.25 mg.
DRUGTacrolimus
Tacrolimus was administrated as Prograf® or Advagraf®, but could not be changed during study.
Myfortic® (MFS) was given as 720-1440 mg/day or 360-1440 mg/day. Cell-Cept® (MMF) was given as 1000-2000 mg/day or 500-2000 mg/day.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Received kidney transplant \> 6 months and \< 3 years prior to study enrollment * Receiving immunosuppressive regimen that includes tacrolimus and mycophenolic acid * Between 18 and 70 years of age * Willing to provide written informed consent
Exclusion criteria
* Patients with an actual serum creatinine ≥ 2 mg/dl and/or eGFR≤ 40 ml/min and/or proteinuria≥ 500mg/day * Patients who suffered from severe humoral and/or cellular rejection (≥ BANFF IIb, recurrent acute rejection or steroid resistant acute rejection in the previous years * Patients who have severe hypercholesterolemia (\>350 mg/dL; \>9 mmol/L) or hypertriglyceridemia (\>500 mg/dL; \>8.5 mmol/L). Patients with controlled hyperlipidemia are acceptable. * Diabetic patients * Woman of child-bearing potential who is planning to become pregnant or is pregnant and/or lactating who is unwilling to use effective means of contraception * Presence of psychiatric illness (i.e., schizophrenia, major depression) that, in the opinion of the site investigator, would interfere with study requirements * Any other medical condition that, in the opinion of the site investigator based on recall or chart review would interfere with completing the study * Receiving any investigational drug or have received any investigational drug within 30 days prior to study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricular Mass Index (LVMI) | Baseline, Month 24 | Left ventricular hypertrophy grade was assessed by echocardiogram where the left ventricular mass index was calculated. The presence of LVM was defined as \> 49.2 g/m\^2.7 in men and \>46.7 g/m\^2.7 in women. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulse Wave Velocity (PWV) | Month 6, month 24 | Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location. The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity. |
| Percentage of Participants With Major Cardiovascular Events (MACE) | Month 24 | The percentage of participants who experienced MACE were reported. MACE included acute myocardial infarction, insertion or replacement of implantable defibrillator, peripheral vascular disorders, congestive heart failure, coronary artery bypass, other events, percutaneous coronary intervention and stroke. |
| Renal Function Measured by Serum Creatinine | Month 6, month 12, month 24 | Serum samples were collected to analyze serum creatinine. |
| Renal Function as Measured by Creatinine Clearance | Month 6, month 12, month 24 | Creatinine clearance was calculated using the Cockroft-Gault formula. |
| Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 6, month 12, month 24 | Estimated GFR was caluclated using the modification of diet in renal disease (MDRD) formula. |
| Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | Baseline, month 6, month 24 | Blood samples were collected to analyze Troponin I and collagen type 1 C-telopeptide (ICTP). A negative change from baseline indicates improvement. |
| Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Baseline, Month 6, month 12, month 24 | Blood pressure was measured using ambulatory blood pressure monitoring (ABPM). A negative change from baseline indicates improvement. |
| Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO) | Baseline, month 6, month 24 | Blood samples were collected to analyze MPO. A negative change from baseline indicates improvement. |
| Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP) | Baseline, month 6, month 24 | Blood samples were collected to analyze NT-proBNP. A negative change from baseline indicates improvement. |
| Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP) | Baseline, month 6, month 24 | Blood samples were collected to analyze PCR. A negative change from baseline indicates improvement. |
| Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP) | Baseline, month 6, month 24 | Blood samples were collected to analyze CRP. A negative change from baseline indicates improvement. |
| Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Month 24 | The incidence of BPAR, graft loss, death and lost to follow-up events was calculated using relative frequency. |
| Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c) | Baseline, month 6, month 24 | Blood samples were collected to analyze HbA1c. A negative change from baseline indicates improvement. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus Participants continued with the same tacrolimus+Mycophenolic acid (MPA) (Myfortic® or Cell-Cept®) doses that were taken before study initiation (tacrolimus levels 4-7 ng/ml). | 36 |
| Everolimus Participants received an initial dose (day 1) of Everolimus (EVL) 2mg at night and tacrolimus (if taking Prograf®, a full dose of Prograf® in the morning and a 50% dose of Prograf® at night; if taking Advagraf®, a 75% dose in the morning. On days 2 and 3, participants took EVL 2 mg twice daily (bid) without tacrolimus. On days 4 and 5, the EVL dose was adjusted and levels maintained between 5-8 ng/mL. Participants also continued with their MPA doses that were taken prior to study initiation. | 35 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 0 | 1 |
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Exclusion criteria | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Serious adverse event | 0 | 1 |
| Overall Study | Sponsor decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Tacrolimus | Everolimus | Total |
|---|---|---|---|
| Age, Continuous | 49.1 Years STANDARD_DEVIATION 12 | 47.4 Years STANDARD_DEVIATION 13.2 | 48.3 Years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 16 Participants | 13 Participants | 29 Participants |
| Sex: Female, Male Male | 20 Participants | 22 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 36 | 24 / 35 |
| serious Total, serious adverse events | 5 / 36 | 8 / 35 |
Outcome results
Primary
Change From Baseline in Left Ventricular Mass Index (LVMI)
Left ventricular hypertrophy grade was assessed by echocardiogram where the left ventricular mass index was calculated. The presence of LVM was defined as \> 49.2 g/m\^2.7 in men and \>46.7 g/m\^2.7 in women. A negative change from baseline indicates improvement.
Time frame: Baseline, Month 24
Population: Participants from the Intent to Treat (ITT) analysis set, who had both baseline and month 24 values, were analyzed. The ITT included participants who received at least one dose of study medication and at least one post baseline LVMI value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tacrolimus | Change From Baseline in Left Ventricular Mass Index (LVMI) | -6.071 g/m^2.7 | Standard Deviation 20.116 |
| Everolimus | Change From Baseline in Left Ventricular Mass Index (LVMI) | -4.008 g/m^2.7 | Standard Deviation 17.61 |
Secondary
Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP)
Blood samples were collected to analyze CRP. A negative change from baseline indicates improvement.
Time frame: Baseline, month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP) | Month 6 (n=27,30) | 0.512 mg/dl | Standard Deviation 2.342 |
| Tacrolimus | Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP) | Month 24 (n=24,24) | 0.100 mg/dl | Standard Deviation 0.469 |
| Everolimus | Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP) | Month 6 (n=27,30) | 0.326 mg/dl | Standard Deviation 1.129 |
| Everolimus | Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP) | Month 24 (n=24,24) | -0.040 mg/dl | Standard Deviation 1.683 |
Secondary
Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP)
Blood samples were collected to analyze Troponin I and collagen type 1 C-telopeptide (ICTP). A negative change from baseline indicates improvement.
Time frame: Baseline, month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | Troponin 1, Month 6 (n=27,30) | 0.000 ng/ml | Standard Deviation 0.01 |
| Tacrolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | Troponin 1, Month 24 (n=24,24) | 0.003 ng/ml | Standard Deviation 0.026 |
| Tacrolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | ICTP, Month 6 (n=27,30) | 0.049 ng/ml | Standard Deviation 0.341 |
| Tacrolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | ICTP, Month 24 (n=24,24) | -0.035 ng/ml | Standard Deviation 0.366 |
| Everolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | ICTP, Month 24 (n=24,24) | -0.125 ng/ml | Standard Deviation 0.323 |
| Everolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | Troponin 1, Month 6 (n=27,30) | -0.006 ng/ml | Standard Deviation 0.026 |
| Everolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | ICTP, Month 6 (n=27,30) | -0.195 ng/ml | Standard Deviation 0.234 |
| Everolimus | Change From Baseline in Cardiovascular Biomarkers: Troponin I and Collagen Type 1 C-telopeptide (ICTP) | Troponin 1, Month 24 (n=24,24) | -0.007 ng/ml | Standard Deviation 0.018 |
Secondary
Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure
Blood pressure was measured using ambulatory blood pressure monitoring (ABPM). A negative change from baseline indicates improvement.
Time frame: Baseline, Month 6, month 12, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Month 6 (n=31,29) | -0.6 mmHg | Standard Deviation 9.1 |
| Tacrolimus | Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Month 12 (n=28,24) | 2.1 mmHg | Standard Deviation 6.9 |
| Tacrolimus | Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Month 24 (n=29,24) | 2.2 mmHg | Standard Deviation 10.6 |
| Everolimus | Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Month 6 (n=31,29) | 3.2 mmHg | Standard Deviation 8.6 |
| Everolimus | Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Month 12 (n=28,24) | 2.7 mmHg | Standard Deviation 10.4 |
| Everolimus | Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure | Month 24 (n=29,24) | 2.0 mmHg | Standard Deviation 8.7 |
Secondary
Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c)
Blood samples were collected to analyze HbA1c. A negative change from baseline indicates improvement.
Time frame: Baseline, month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c) | Month 6 (n=20,22) | 0.015 Percentage of HbA1c | Standard Deviation 0.184 |
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c) | Month12 (n=22,20) | 0.045 Percentage of HbA1c | Standard Deviation 0.237 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c) | Month 6 (n=20,22) | 0.159 Percentage of HbA1c | Standard Deviation 0.346 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c) | Month12 (n=22,20) | 0.185 Percentage of HbA1c | Standard Deviation 0.407 |
Secondary
Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO)
Blood samples were collected to analyze MPO. A negative change from baseline indicates improvement.
Time frame: Baseline, month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO) | Month 6 (n=27,30) | 0.433 U/mL | Standard Deviation 2.189 |
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO) | Month 24 (n=24,24) | -0.329 U/mL | Standard Deviation 0.28 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO) | Month 6 (n=27,30) | -0.093 U/mL | Standard Deviation 1.158 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO) | Month 24 (n=24,24) | -0.642 U/mL | Standard Deviation 0.972 |
Secondary
Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP)
Blood samples were collected to analyze NT-proBNP. A negative change from baseline indicates improvement.
Time frame: Baseline, month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP) | Month 6 (n=27,30) | 21.604 pg/mL | Standard Deviation 294.82 |
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP) | Month 24 (n=24,24) | -80.20 pg/mL | Standard Deviation 424.24 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP) | Month 6 (n=27,30) | -79.10 pg/mL | Standard Deviation 401.44 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, N-terminal Pro-brain Natriuretic Peptide Fraction (NT-proBNP) | Month 24 (n=24,24) | -193.3 pg/mL | Standard Deviation 590.9 |
Secondary
Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP)
Blood samples were collected to analyze PCR. A negative change from baseline indicates improvement.
Time frame: Baseline, month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at both baseline and the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP) | Month 6 (n=27,30) | -13.82 ug/l | Standard Deviation 34.11 |
| Tacrolimus | Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP) | Month 24 (n=24,24) | -13.65 ug/l | Standard Deviation 40.675 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP) | Month 6 (n=27,30) | -33.36 ug/l | Standard Deviation 33.227 |
| Everolimus | Change From Baseline in the Cardiovascular Biomarker, Type 1 Procollagen Amino-terminal-propeptide (PINP) | Month 24 (n=24,24) | -28.17 ug/l | Standard Deviation 30.381 |
Secondary
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up
The incidence of BPAR, graft loss, death and lost to follow-up events was calculated using relative frequency.
Time frame: Month 24
Population: Intent to Treat (ITT): The ITT included participants who received at least one dose of study medication and at least one post baseline LVMI value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tacrolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | BPAR | 0.00 Percentage of participants |
| Tacrolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Graft loss | 0.00 Percentage of participants |
| Tacrolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Deaths | 0.00 Percentage of participants |
| Tacrolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Lost to follow-up | 3.13 Percentage of participants |
| Everolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Lost to follow-up | 0.00 Percentage of participants |
| Everolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | BPAR | 0.00 Percentage of participants |
| Everolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Deaths | 0.00 Percentage of participants |
| Everolimus | Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up | Graft loss | 0.00 Percentage of participants |
Secondary
Percentage of Participants With Major Cardiovascular Events (MACE)
The percentage of participants who experienced MACE were reported. MACE included acute myocardial infarction, insertion or replacement of implantable defibrillator, peripheral vascular disorders, congestive heart failure, coronary artery bypass, other events, percutaneous coronary intervention and stroke.
Time frame: Month 24
Population: The Intent to Treat (ITT) analysis set: The ITT included participants who received at least one dose of study medication and had at least one post baseline LVMI value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus | Percentage of Participants With Major Cardiovascular Events (MACE) | 0.00 Percentage of participants |
| Everolimus | Percentage of Participants With Major Cardiovascular Events (MACE) | 0.00 Percentage of participants |
Secondary
Pulse Wave Velocity (PWV)
Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location. The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity.
Time frame: Month 6, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Pulse Wave Velocity (PWV) | Month 6 (n=31,30) | 7.01 m/sec | Standard Deviation 1.62 |
| Tacrolimus | Pulse Wave Velocity (PWV) | Month 24 (n=28,25) | 7.58 m/sec | Standard Deviation 1.68 |
| Everolimus | Pulse Wave Velocity (PWV) | Month 6 (n=31,30) | 7.40 m/sec | Standard Deviation 1.62 |
| Everolimus | Pulse Wave Velocity (PWV) | Month 24 (n=28,25) | 7.06 m/sec | Standard Deviation 1.74 |
Secondary
Renal Function as Measured by Creatinine Clearance
Creatinine clearance was calculated using the Cockroft-Gault formula.
Time frame: Month 6, month 12, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Renal Function as Measured by Creatinine Clearance | Month 6 (n=29,25) | 64.841 mg/min | Standard Deviation 16.163 |
| Tacrolimus | Renal Function as Measured by Creatinine Clearance | Month 12 (n=28,25) | 65.037 mg/min | Standard Deviation 15.866 |
| Tacrolimus | Renal Function as Measured by Creatinine Clearance | Month 24 (n=28,24) | 66.933 mg/min | Standard Deviation 13.264 |
| Everolimus | Renal Function as Measured by Creatinine Clearance | Month 6 (n=29,25) | 76.618 mg/min | Standard Deviation 27.708 |
| Everolimus | Renal Function as Measured by Creatinine Clearance | Month 12 (n=28,25) | 73.363 mg/min | Standard Deviation 25.989 |
| Everolimus | Renal Function as Measured by Creatinine Clearance | Month 24 (n=28,24) | 72.910 mg/min | Standard Deviation 23.926 |
Secondary
Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR)
Estimated GFR was caluclated using the modification of diet in renal disease (MDRD) formula.
Time frame: Month 6, month 12, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 6 (n=33,29) | 55.648 mL/min/1.73m^2 | Standard Deviation 11.244 |
| Tacrolimus | Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 12 (n=32,28) | 57.757 mL/min/1.73m^2 | Standard Deviation 11.391 |
| Tacrolimus | Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 24 (n=31,26) | 57.727 mL/min/1.73m^2 | Standard Deviation 10.498 |
| Everolimus | Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 6 (n=33,29) | 63.781 mL/min/1.73m^2 | Standard Deviation 18.38 |
| Everolimus | Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 12 (n=32,28) | 61.225 mL/min/1.73m^2 | Standard Deviation 19.239 |
| Everolimus | Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) | Month 24 (n=31,26) | 60.779 mL/min/1.73m^2 | Standard Deviation 17.023 |
Secondary
Renal Function Measured by Serum Creatinine
Serum samples were collected to analyze serum creatinine.
Time frame: Month 6, month 12, month 24
Population: Participants from the safety analysis set were considered for this analysis. The safety analysis set included participants who received at least one dose of study medication. For each time point, only participants, who had values at the given time point, were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus | Renal Function Measured by Serum Creatinine | Month 6 (n=33,29) | 1.232 mg/dl | Standard Deviation 0.272 |
| Tacrolimus | Renal Function Measured by Serum Creatinine | Month 12 (n=32,28) | 1.231 mg/dl | Standard Deviation 0.278 |
| Tacrolimus | Renal Function Measured by Serum Creatinine | Month 24 (n= 31,26) | 1.217 mg/dl | Standard Deviation 0.235 |
| Everolimus | Renal Function Measured by Serum Creatinine | Month 6 (n=33,29) | 1.234 mg/dl | Standard Deviation 0.36 |
| Everolimus | Renal Function Measured by Serum Creatinine | Month 12 (n=32,28) | 1.256 mg/dl | Standard Deviation 0.367 |
| Everolimus | Renal Function Measured by Serum Creatinine | Month 24 (n= 31,26) | 1.260 mg/dl | Standard Deviation 0.358 |