Trial Outcomes & Findings for Evaluation of Early Conversion to Everolimus From Cyclosporine in de Novo Renal Transplant Recipients (NCT NCT00634920)
NCT ID: NCT00634920
Last Updated: 2014-08-13
Results Overview
To compare the efficacy between treatment regimens by assessing the difference in renal function evaluated by mean measured glomerular filtration rate (mGFR) 12 months after renal transplantation (TX). The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
204 participants
Primary outcome timeframe
Month 12
Results posted on
2014-08-13
Participant Flow
The study consisted of 2 periods, period 1: TX to Week 7 ± 7 days post-TX and period 2: Week 7 ± 7 days post-TX to Month 36. 341 patients were enrolled in this study. 204 randomized to receive study treatment: 104 in the everolimus group, 100 in the control group. 2 patients in everolimus group did not receive at least one dose of study treatment.
Participant milestones
| Measure |
Everolimus (CNI-free)
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
Pre-Randomized Patients
All patients received induction therapy with 20 mg basiliximab on Day 0 prior to reperfusion and 20 mg at Day 4 post-TX (transplatation), and commenced on an immunosuppressive regimen consisting of: CsA (based on trough levels C0-h 100-250 ng/mL or C2-h 900 1300 ng/mL, according to local method), EC MPS (target dose 1440 mg/day, minimum dose 1080 mg/day at the time of randomization), Corticosteroids (a minimum dose of 10 mg prednisolone or equivalent was given at time of randomization).
|
|---|---|---|---|
|
Period 1 - Pre-Randomization
STARTED
|
0
|
0
|
341
|
|
Period 1 - Pre-Randomization
COMPLETED
|
0
|
0
|
204
|
|
Period 1 - Pre-Randomization
NOT COMPLETED
|
0
|
0
|
137
|
|
Period 2 - Post-Randomization
STARTED
|
104
|
100
|
0
|
|
Period 2 - Post-Randomization
Full Analysis Set (FAS)
|
92
|
90
|
0
|
|
Period 2 - Post-Randomization
COMPLETED
|
43
|
68
|
0
|
|
Period 2 - Post-Randomization
NOT COMPLETED
|
61
|
32
|
0
|
Reasons for withdrawal
| Measure |
Everolimus (CNI-free)
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
Pre-Randomized Patients
All patients received induction therapy with 20 mg basiliximab on Day 0 prior to reperfusion and 20 mg at Day 4 post-TX (transplatation), and commenced on an immunosuppressive regimen consisting of: CsA (based on trough levels C0-h 100-250 ng/mL or C2-h 900 1300 ng/mL, according to local method), EC MPS (target dose 1440 mg/day, minimum dose 1080 mg/day at the time of randomization), Corticosteroids (a minimum dose of 10 mg prednisolone or equivalent was given at time of randomization).
|
|---|---|---|---|
|
Period 1 - Pre-Randomization
Adverse Event
|
0
|
0
|
36
|
|
Period 1 - Pre-Randomization
Wound healing problems
|
0
|
0
|
16
|
|
Period 1 - Pre-Randomization
Rejections
|
0
|
0
|
55
|
|
Period 1 - Pre-Randomization
Withdrawal by Subject
|
0
|
0
|
21
|
|
Period 1 - Pre-Randomization
Non-Compliance
|
0
|
0
|
3
|
|
Period 1 - Pre-Randomization
Other issues
|
0
|
0
|
6
|
|
Period 2 - Post-Randomization
Adverse Event
|
37
|
9
|
0
|
|
Period 2 - Post-Randomization
Rejection
|
11
|
5
|
0
|
|
Period 2 - Post-Randomization
Death
|
2
|
5
|
0
|
|
Period 2 - Post-Randomization
consent withdrawal, non compliance
|
9
|
13
|
0
|
|
Period 2 - Post-Randomization
Patients did not receive study drug
|
2
|
0
|
0
|
Baseline Characteristics
Evaluation of Early Conversion to Everolimus From Cyclosporine in de Novo Renal Transplant Recipients
Baseline characteristics by cohort
| Measure |
Everolimus (CNI-free)
n=104 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=100 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
Not Randomized Patients
n=137 Participants
This group included patients in whom a renal TX was performed but who did not qualify for randomization at Visit 2. This group was to be described with respect to treatment, reason for not randomized and outcome variables calculated or measured GFR, whichever was feasible, BPAR, graft loss or death at 12 months (no outcome variables were collected for this population
|
Total
n=341 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.0 Years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
53.3 Years
STANDARD_DEVIATION 12.3 • n=7 Participants
|
56.3 Years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
55.0 Years
STANDARD_DEVIATION 12.0 • n=4 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
103 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
70 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
238 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
101 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
136 Participants
n=5 Participants
|
337 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Oriental
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Month 12Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
To compare the efficacy between treatment regimens by assessing the difference in renal function evaluated by mean measured glomerular filtration rate (mGFR) 12 months after renal transplantation (TX). The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Measured Glomerular Filtration Rate
|
51.5 mL/min/1.73m^2
Standard Deviation 14.4
|
47.8 mL/min/1.73m^2
Standard Deviation 15.4
|
SECONDARY outcome
Timeframe: Month 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR). Patients who did not provide mGFR assessment at M36 visit were excluded from the analysis.
Progression of renal function measured by mean mGFR at 36 months after renal TX. The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=87 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Measured Glomerular Filtration Rate
|
48.2 mL/min/1.73m^2
Standard Deviation 14.7
|
46.1 mL/min/1.73m^2
Standard Deviation 17.0
|
SECONDARY outcome
Timeframe: Months 12, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
The GFR was calculated according to the Modification of Diet in Renal Disease Study Group (MDRD) method, the Cockcroft-Gault method, and the Nankivell formula. cGFR was calculated from blood samples collected at predefined time points.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Calculated Glomerular Filtration Rate
MDRD M12
|
65.0 mL/min/1.73m^2
Standard Deviation 19.9
|
60.1 mL/min/1.73m^2
Standard Deviation 19.7
|
|
Calculated Glomerular Filtration Rate
MDRD M36
|
59.4 mL/min/1.73m^2
Standard Deviation 20.1
|
57.4 mL/min/1.73m^2
Standard Deviation 20.2
|
|
Calculated Glomerular Filtration Rate
Cockcroft-Gault M12
|
45.4 mL/min/1.73m^2
Standard Deviation 14.6
|
45.6 mL/min/1.73m^2
Standard Deviation 15.4
|
|
Calculated Glomerular Filtration Rate
Cockcroft-Gault M36
|
43.1 mL/min/1.73m^2
Standard Deviation 16.1
|
42.1 mL/min/1.73m^2
Standard Deviation 13.1
|
|
Calculated Glomerular Filtration Rate
Nankivel M12
|
66.3 mL/min/1.73m^2
Standard Deviation 19.2
|
61.8 mL/min/1.73m^2
Standard Deviation 20.5
|
|
Calculated Glomerular Filtration Rate
Nankivel M36
|
61.8 mL/min/1.73m^2
Standard Deviation 20.9
|
58.9 mL/min/1.73m^2
Standard Deviation 20.0
|
SECONDARY outcome
Timeframe: Week 7, Week 52, Month 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Change in renal progression measured by mean mGFR from week 7 to Month 36
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Progression of Measured Glomerular Filtration Rate
Week 7
|
46.3 mL/min/1.73m^2
Standard Deviation 13.0
|
47.8 mL/min/1.73m^2
Standard Deviation 15.0
|
|
Progression of Measured Glomerular Filtration Rate
Week 52
|
51.5 mL/min/1.73m^2
Standard Deviation 14.4
|
47.8 mL/min/1.73m^2
Standard Deviation 15.4
|
|
Progression of Measured Glomerular Filtration Rate
Change from week 7 to Week 52
|
5.6 mL/min/1.73m^2
Standard Deviation 11.5
|
0.0 mL/min/1.73m^2
Standard Deviation 12.9
|
|
Progression of Measured Glomerular Filtration Rate
Month 36
|
48.2 mL/min/1.73m^2
Standard Deviation 14.7
|
46.1 mL/min/1.73m^2
Standard Deviation 17.0
|
|
Progression of Measured Glomerular Filtration Rate
Change from week 7 to Month 36
|
1.3 mL/min/1.73m^2
Standard Deviation 14.0
|
-1.7 mL/min/1.73m^2
Standard Deviation 15.4
|
SECONDARY outcome
Timeframe: Month 12, Month 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Assessed by protocol biopsies findings (Banff 1997 lesion scores and morphometry of the interstitial space)
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants Who Developed CAN (Chronic Allograft Nephropathy)
Month 12
|
1.0 Percentage of participants
|
1.0 Percentage of participants
|
|
Percentage of Participants Who Developed CAN (Chronic Allograft Nephropathy)
Month 36
|
59.0 Percentage of participants
|
64.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
A BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III (Banff 97 classification). Biopsy graded IA: Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IB: Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IIA: Mild to moderate intimal arteritis. Biopsy graded IIB: Severe intimal arteritis comprising \> 25% of the lumenal area.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 12: lA
|
19.6 Percentage of participants
|
4.4 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 12: lB
|
10.9 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 12: llA
|
2.2 Percentage of participants
|
2.2 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 12: llB
|
2.2 Percentage of participants
|
1.1 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 24: lA
|
5.4 Percentage of participants
|
4.4 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 24: lB
|
1.1 Percentage of participants
|
3.3 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 36: lA
|
2.2 Percentage of participants
|
1.1 Percentage of participants
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Month 36: lB
|
1.1 Percentage of participants
|
0.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, the day of nephrectomy was the day of graft loss. Graft loss was considered an SAE (serious adverse event).
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants With Graft Loss or Death
Month 12: Event First Year
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Graft Loss or Death
Month 12: No Event First Year
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With Graft Loss or Death
Month 24: Event Second Year
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
Percentage of Participants With Graft Loss or Death
Month 24: No Event Second Year
|
98.9 Percentage of participants
|
98.9 Percentage of participants
|
|
Percentage of Participants With Graft Loss or Death
Month 36: Event Third Year
|
0.0 Percentage of participants
|
2.2 Percentage of participants
|
|
Percentage of Participants With Graft Loss or Death
Month 36: No Event Third Year
|
100.0 Percentage of participants
|
97.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Treatment failure was defined as graft loss or death.Time to treatment failure is shown as mean time to treatment failure.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Time to Treatment Failure
|
972.7 Days
Standard Error 7.76
|
959.5 Days
Standard Error 7.76
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Treatment failure was defined as graft loss or death.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants With Treatment Failures
Month 12: No Failure
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With Treatment Failures
Month 12: Failure
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Treatment Failures
Month 24: No Failure
|
98.8 Percentage of participants
|
98.8 Percentage of participants
|
|
Percentage of Participants With Treatment Failures
Month 24: Failure
|
1.2 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Treatment Failures
Month 36: No Failure
|
98.8 Percentage of participants
|
96.7 Percentage of participants
|
|
Percentage of Participants With Treatment Failures
Month 36: Failure
|
1.2 Percentage of participants
|
3.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
This is the time to first diagnosed malignancy. Malignancies (skin- or solid cancer) were listed whether they reoccurred in situ, were metastatic or de novo. This is shown as mean time.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Time to First Malignancy
|
35.5 Months
Standard Error 0.63
|
35.1 Months
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Blood lipid levels of patients in both groups for Apolipoprotein (Apo) A1 and B.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Lipid Profile for Apolipoprotein
Month 12: Apolipoprotein A1
|
1.59 g/L
Standard Deviation 0.31
|
1.46 g/L
Standard Deviation 0.26
|
|
Lipid Profile for Apolipoprotein
Month 24: Apolipoprotein A1
|
1.55 g/L
Standard Deviation 0.29
|
1.36 g/L
Standard Deviation 0.06
|
|
Lipid Profile for Apolipoprotein
Month 36: Apolipoprotein A1
|
1.70 g/L
Standard Deviation 0.39
|
1.56 g/L
Standard Deviation 0.33
|
|
Lipid Profile for Apolipoprotein
Month 12: Apolipoprotein B
|
0.935 g/L
Standard Deviation 0.235
|
0.923 g/L
Standard Deviation 0.258
|
|
Lipid Profile for Apolipoprotein
Month 24: Apolipoprotein B (
|
1.178 g/L
Standard Deviation 0.225
|
1.058 g/L
Standard Deviation 0.263
|
|
Lipid Profile for Apolipoprotein
Month 36: Apolipoprotein B
|
0.984 g/L
Standard Deviation 0.211
|
0.934 g/L
Standard Deviation 0.206
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Blood lipid levels of patients in both groups: HDL-C, LDL-C,Total cholesterol, and triglycerides.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 12: HDL Cholesterol
|
1.486 mmol/L
Standard Deviation 0.446
|
1.419 mmol/L
Standard Deviation 0.409
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 24: HDL Cholesterol
|
1.477 mmol/L
Standard Deviation 0.437
|
1.409 mmol/L
Standard Deviation 0.411
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 36: HDL Cholesterol
|
1.495 mmol/L
Standard Deviation 0.440
|
1.529 mmol/L
Standard Deviation 0.518
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 12: LDL Cholesterol
|
3.569 mmol/L
Standard Deviation 1.390
|
3.130 mmol/L
Standard Deviation 0.962
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 24: LDL Cholesterol
|
3.381 mmol/L
Standard Deviation 1.139
|
2.925 mmol/L
Standard Deviation 1.043
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 36: LDL Cholesterol
|
3.206 mmol/L
Standard Deviation 0.945
|
2.822 mmol/L
Standard Deviation 0.789
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 12: Total Cholesterol
|
6.091 mmol/L
Standard Deviation 1.650
|
5.318 mmol/L
Standard Deviation 1.067
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 24: Total Cholesterol
|
5.823 mmol/L
Standard Deviation 1.377
|
5.112 mmol/L
Standard Deviation 1.096
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 36: Total Cholesterol
|
5.595 mmol/L
Standard Deviation 1.396
|
4.830 mmol/L
Standard Deviation 1.166
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 12: Triglycerides
|
2.461 mmol/L
Standard Deviation 1.620
|
1.868 mmol/L
Standard Deviation 0.932
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 24: Triglycerides
|
2.288 mmol/L
Standard Deviation 1.400
|
1.757 mmol/L
Standard Deviation 0.958
|
|
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Month 36: Triglycerides
|
2.164 mmol/L
Standard Deviation 1.256
|
1.580 mmol/L
Standard Deviation 0.853
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Number of Lipid-lowering Drugs Taken
Month 12
|
0.9 Number of lipid-lowering drugs
Standard Deviation 0.4
|
0.8 Number of lipid-lowering drugs
Standard Deviation 0.4
|
|
Number of Lipid-lowering Drugs Taken
Month 24
|
1.0 Number of lipid-lowering drugs
Standard Deviation 0.4
|
0.9 Number of lipid-lowering drugs
Standard Deviation 0.4
|
|
Number of Lipid-lowering Drugs Taken
Month 36
|
0.9 Number of lipid-lowering drugs
Standard Deviation 0.5
|
0.8 Number of lipid-lowering drugs
Standard Deviation 0.4
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants on Lipid-lowering Drugs
Month 12
|
75.0 Percentage of participants
0.4
|
60.0 Percentage of participants
0.4
|
|
Percentage of Participants on Lipid-lowering Drugs
Month 24
|
78.0 Percentage of participants
0.4
|
65.0 Percentage of participants
0.4
|
|
Percentage of Participants on Lipid-lowering Drugs
Month 36
|
73.0 Percentage of participants
0.5
|
63.0 Percentage of participants
0.4
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Number of Antihypertensive Drugs Taken
Month 12
|
2.5 Number of antihypertensive dugs
Standard Deviation 1.4
|
2.5 Number of antihypertensive dugs
Standard Deviation 1.1
|
|
Number of Antihypertensive Drugs Taken
Month 24
|
2.5 Number of antihypertensive dugs
Standard Deviation 1.3
|
2.4 Number of antihypertensive dugs
Standard Deviation 1.1
|
|
Number of Antihypertensive Drugs Taken
Month 36
|
2.0 Number of antihypertensive dugs
Standard Deviation 1.4
|
2.2 Number of antihypertensive dugs
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants on Antihypertensive Drugs
Month 24: No antihypertensive drugs
|
4.2 Percentage of participants
|
5.3 Percentage of participants
|
|
Percentage of Participants on Antihypertensive Drugs
Month 24: Has antihypertensive drugs
|
95.8 Percentage of participants
|
94.7 Percentage of participants
|
|
Percentage of Participants on Antihypertensive Drugs
Month 12: No antihypertensive drugs
|
9.2 Percentage of participants
|
3.3 Percentage of participants
|
|
Percentage of Participants on Antihypertensive Drugs
Month 12: Has antihypertensive drugs
|
90.8 Percentage of participants
|
96.7 Percentage of participants
|
|
Percentage of Participants on Antihypertensive Drugs
Month 36: No antihypertensive drugs
|
15.6 Percentage of participants
|
12.8 Percentage of participants
|
|
Percentage of Participants on Antihypertensive Drugs
Month 36: Has antihypertensive drugs
|
84.4 Percentage of participants
|
87.2 Percentage of participants
|
SECONDARY outcome
Timeframe: Months 12, 24, 36Population: The safety population (SAF) consists of all patients in whom TX was performed and who were randomized and treated with at least one dose of randomized treatment.
Proteinuria is when a large amount of protein, that should remain circulating in a person's blood, is "spilled" into their urine and eliminated from the body.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=102 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=100 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Proteinuria (Measured as Urine Albumin/Creatinine Ratio (mg/mmol))
Month 12
|
17.31 mg/mmol
Standard Deviation 29.39
|
11.27 mg/mmol
Standard Deviation 22.92
|
|
Proteinuria (Measured as Urine Albumin/Creatinine Ratio (mg/mmol))
Month 24
|
62.83 mg/mmol
Standard Deviation 178.62
|
24.55 mg/mmol
Standard Deviation 52.07
|
|
Proteinuria (Measured as Urine Albumin/Creatinine Ratio (mg/mmol))
Month 36
|
78.78 mg/mmol
Standard Deviation 357.45
|
80.73 mg/mmol
Standard Deviation 534.30
|
SECONDARY outcome
Timeframe: Month 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Venous blood was drawn for donor specific (DSA) measurements prior to transplantation and at the final visit (36 months). The blood sample was first screened for the presence of PRA i.e. donor specific Immunoglobulin-G antibodies against specific HLA antigens. If PRA antibodies were detected, the blood sample was tested for specific DSAs on single antigen Luminex beads (coated with single HLA class I or II molecules). In this way, the specificity of these antibodies could be determined.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Percentage of Participants Who Had Donor Specific Antibodies (DSA)
ND (not done)
|
7.0 Percentage of participants
|
9.0 Percentage of participants
|
|
Percentage of Participants Who Had Donor Specific Antibodies (DSA)
Negative
|
78.0 Percentage of participants
|
70.0 Percentage of participants
|
|
Percentage of Participants Who Had Donor Specific Antibodies (DSA)
Positive
|
15.0 Percentage of participants
|
21.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Before randomization, Months 12, 36Population: The full analysis set (FAS) population consists of all randomized patients who received at least one dose of any immunosuppressive therapy after TX and have both baseline and Month 12 assessment of the primary efficacy variable (renal function based on mGFR).
Health-related QoL was assessed using the EQ-5D questionnaire. The EQ-5D self-report questionnaire consists of the EQ-5D descriptive system that measures health-related quality of life on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which can take one of three responses. The responses record three levels of severity (no problems/moderate problems/severe problems) within a particular EQ-5D dimension. Scores are transformed to a range of 0-1, in which higher scores reflect better health status.
Outcome measures
| Measure |
Everolimus (CNI-free)
n=92 Participants
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
Control (CsA)
n=90 Participants
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
|---|---|---|
|
Health-related Quality of Life (QoL) as Measured by EuroQoL EQ-5D
Before Randomization (Week 7)
|
0.8430 scores on a scale
Standard Deviation 0.1539
|
0.8693 scores on a scale
Standard Deviation 0.1583
|
|
Health-related Quality of Life (QoL) as Measured by EuroQoL EQ-5D
Month 12
|
0.8155 scores on a scale
Standard Deviation 0.1605
|
0.8470 scores on a scale
Standard Deviation 0.2239
|
|
Health-related Quality of Life (QoL) as Measured by EuroQoL EQ-5D
Month 36
|
0.8285 scores on a scale
Standard Deviation 0.2303
|
0.8422 scores on a scale
Standard Deviation 0.1941
|
Adverse Events
Control (CsA)
Serious events: 65 serious events
Other events: 88 other events
Deaths: 0 deaths
Everolimus (CNI-free)
Serious events: 72 serious events
Other events: 93 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control (CsA)
n=100 participants at risk
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
Everolimus (CNI-free)
n=102 participants at risk
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
1/100
|
0.00%
0/102
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.0%
1/100
|
0.00%
0/102
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.0%
3/100
|
0.00%
0/102
|
|
Cardiac disorders
Acute myocardial infarction
|
1.0%
1/100
|
0.98%
1/102
|
|
Cardiac disorders
Angina pectoris
|
1.0%
1/100
|
0.00%
0/102
|
|
Cardiac disorders
Atrial fibrillation
|
1.0%
1/100
|
2.9%
3/102
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/100
|
0.98%
1/102
|
|
Cardiac disorders
Cardiac failure
|
1.0%
1/100
|
0.98%
1/102
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/100
|
0.98%
1/102
|
|
Cardiac disorders
Supraventricular tachycardia
|
1.0%
1/100
|
0.00%
0/102
|
|
Cardiac disorders
Ventricular fibrillation
|
1.0%
1/100
|
0.00%
0/102
|
|
Congenital, familial and genetic disorders
Polycystic liver disease
|
1.0%
1/100
|
0.00%
0/102
|
|
Ear and labyrinth disorders
Vertigo
|
1.0%
1/100
|
0.00%
0/102
|
|
Endocrine disorders
Hyperparathyroidism
|
1.0%
1/100
|
0.00%
0/102
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Abdominal pain
|
2.0%
2/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Colitis
|
1.0%
1/100
|
0.00%
0/102
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Diabetic gastroparesis
|
1.0%
1/100
|
0.00%
0/102
|
|
Gastrointestinal disorders
Diarrhoea
|
1.0%
1/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
1.0%
1/100
|
0.00%
0/102
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/100
|
0.98%
1/102
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/100
|
2.0%
2/102
|
|
General disorders
Chest pain
|
2.0%
2/100
|
3.9%
4/102
|
|
General disorders
Death
|
1.0%
1/100
|
0.98%
1/102
|
|
General disorders
General physical health deterioration
|
0.00%
0/100
|
2.9%
3/102
|
|
General disorders
Metaplasia
|
1.0%
1/100
|
0.00%
0/102
|
|
General disorders
Pain
|
1.0%
1/100
|
0.98%
1/102
|
|
General disorders
Pyrexia
|
0.00%
0/100
|
6.9%
7/102
|
|
Hepatobiliary disorders
Cholelithiasis
|
2.0%
2/100
|
0.00%
0/102
|
|
Immune system disorders
Graft versus host disease
|
1.0%
1/100
|
0.00%
0/102
|
|
Immune system disorders
Transplant rejection
|
9.0%
9/100
|
3.9%
4/102
|
|
Infections and infestations
Abscess
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Acute tonsillitis
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
BK virus infection
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Bronchitis
|
0.00%
0/100
|
2.0%
2/102
|
|
Infections and infestations
Campylobacter infection
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Clostridium colitis
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Cystitis
|
2.0%
2/100
|
0.98%
1/102
|
|
Infections and infestations
Cytomegalovirus gastroenteritis
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Cytomegalovirus infection
|
6.0%
6/100
|
3.9%
4/102
|
|
Infections and infestations
Device related infection
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Epstein-Barr viraemia
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Erysipelas
|
1.0%
1/100
|
0.98%
1/102
|
|
Infections and infestations
Gangrene
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Gastroenteritis
|
3.0%
3/100
|
7.8%
8/102
|
|
Infections and infestations
Gastroenteritis caliciviral
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Gastroenteritis salmonella
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
H1N1 influenza
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Herpes simplex
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/100
|
2.0%
2/102
|
|
Infections and infestations
Infected lymphocele
|
0.00%
0/100
|
2.0%
2/102
|
|
Infections and infestations
Infection
|
1.0%
1/100
|
3.9%
4/102
|
|
Infections and infestations
Lung infection
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
0.00%
0/100
|
2.0%
2/102
|
|
Infections and infestations
Pneumonia
|
6.0%
6/100
|
14.7%
15/102
|
|
Infections and infestations
Pyelonephritis
|
5.0%
5/100
|
3.9%
4/102
|
|
Infections and infestations
Pyelonephritis acute
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Rectal abscess
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Renal cyst infection
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Sepsis
|
2.0%
2/100
|
4.9%
5/102
|
|
Infections and infestations
Subcutaneous abscess
|
1.0%
1/100
|
0.00%
0/102
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/100
|
2.0%
2/102
|
|
Infections and infestations
Urinary tract infection
|
10.0%
10/100
|
9.8%
10/102
|
|
Infections and infestations
Urosepsis
|
3.0%
3/100
|
3.9%
4/102
|
|
Infections and infestations
Viral infection
|
0.00%
0/100
|
0.98%
1/102
|
|
Infections and infestations
Wound infection
|
0.00%
0/100
|
3.9%
4/102
|
|
Injury, poisoning and procedural complications
Complications of transplant surgery
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.0%
1/100
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Graft complication
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
1.0%
1/100
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
Poisoning
|
1.0%
1/100
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Postoperative fever
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
1.0%
1/100
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
Radius fracture
|
1.0%
1/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Rib fracture
|
1.0%
1/100
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/100
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
2.0%
2/100
|
0.00%
0/102
|
|
Investigations
Blood creatinine increased
|
4.0%
4/100
|
7.8%
8/102
|
|
Investigations
Norovirus test positive
|
1.0%
1/100
|
0.00%
0/102
|
|
Metabolism and nutrition disorders
Dehydration
|
3.0%
3/100
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/100
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
1.0%
1/100
|
0.00%
0/102
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/100
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.0%
1/100
|
0.00%
0/102
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.0%
2/100
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
1.0%
1/100
|
0.98%
1/102
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/100
|
0.98%
1/102
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/100
|
0.98%
1/102
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/100
|
0.98%
1/102
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
1.0%
1/100
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.00%
0/100
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
2.0%
2/100
|
4.9%
5/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
1.0%
1/100
|
0.00%
0/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.0%
1/100
|
0.00%
0/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia
|
0.00%
0/100
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma
|
1.0%
1/100
|
0.00%
0/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/100
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
1.0%
1/100
|
0.00%
0/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parathyroid tumour benign
|
1.0%
1/100
|
0.00%
0/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.00%
0/100
|
0.98%
1/102
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
3.0%
3/100
|
2.0%
2/102
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.0%
1/100
|
2.0%
2/102
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Cerebrovascular accident
|
1.0%
1/100
|
0.98%
1/102
|
|
Nervous system disorders
Cerebrovascular disorder
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Convulsion
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Diabetic neuropathy
|
1.0%
1/100
|
0.00%
0/102
|
|
Nervous system disorders
Encephalitis
|
1.0%
1/100
|
0.00%
0/102
|
|
Nervous system disorders
Epilepsy
|
1.0%
1/100
|
2.0%
2/102
|
|
Nervous system disorders
Monoparesis
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Presyncope
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/100
|
0.98%
1/102
|
|
Nervous system disorders
Syncope
|
0.00%
0/100
|
0.98%
1/102
|
|
Psychiatric disorders
Depression
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Bladder perforation
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Glomerulonephritis rapidly progressive
|
1.0%
1/100
|
0.00%
0/102
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Hydronephrosis
|
1.0%
1/100
|
2.9%
3/102
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Renal cyst
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/100
|
2.0%
2/102
|
|
Renal and urinary disorders
Urethral stenosis
|
0.00%
0/100
|
0.98%
1/102
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/100
|
0.98%
1/102
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.0%
1/100
|
0.00%
0/102
|
|
Reproductive system and breast disorders
Breast enlargement
|
1.0%
1/100
|
0.00%
0/102
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.0%
1/100
|
0.00%
0/102
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/100
|
0.98%
1/102
|
|
Surgical and medical procedures
Knee arthroplasty
|
1.0%
1/100
|
0.00%
0/102
|
|
Surgical and medical procedures
Manual lymphatic drainage
|
1.0%
1/100
|
0.00%
0/102
|
|
Surgical and medical procedures
Nephrectomy
|
1.0%
1/100
|
0.00%
0/102
|
|
Surgical and medical procedures
Transurethral prostatectomy
|
1.0%
1/100
|
0.00%
0/102
|
|
Surgical and medical procedures
Vesicoureteral reflux surgery
|
0.00%
0/100
|
0.98%
1/102
|
|
Vascular disorders
Arterial stenosis
|
1.0%
1/100
|
0.00%
0/102
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/100
|
0.98%
1/102
|
|
Vascular disorders
Haematoma
|
0.00%
0/100
|
0.98%
1/102
|
|
Vascular disorders
Lymphocele
|
3.0%
3/100
|
3.9%
4/102
|
|
Vascular disorders
Thrombosis
|
0.00%
0/100
|
0.98%
1/102
|
|
Vascular disorders
Vena cava thrombosis
|
0.00%
0/100
|
0.98%
1/102
|
Other adverse events
| Measure |
Control (CsA)
n=100 participants at risk
All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the control group continued on the prior immunosuppressive regimen given before randomization. Conventional treatment arm with cyclosporine (CsA), mycophenolate (Myfortic) and corticosteroids continued for the entire 36 months study period.
|
Everolimus (CNI-free)
n=102 participants at risk
This investigational drug was provided by Novartis. All patients received induction therapy with basiliximab, and commenced on an immunosuppressive regimen consisting of CsA, EC-MPS and corticosteroids before they were randomized. After randomization patients in the everolimus group (CNI-free regimen) were treated with everolimus (Certican) EC MPS and corticosteroids. Patients randomized to this arm 7 weeks after renal transplantation will do an overnight switch from cyclosporine to everolimus.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
12.0%
12/100
|
23.5%
24/102
|
|
Blood and lymphatic system disorders
Leukopenia
|
10.0%
10/100
|
14.7%
15/102
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/100
|
13.7%
14/102
|
|
Gastrointestinal disorders
Diarrhoea
|
15.0%
15/100
|
11.8%
12/102
|
|
Gastrointestinal disorders
Gingival hyperplasia
|
10.0%
10/100
|
0.00%
0/102
|
|
General disorders
Fatigue
|
8.0%
8/100
|
2.9%
3/102
|
|
General disorders
Oedema
|
4.0%
4/100
|
12.7%
13/102
|
|
General disorders
Oedema peripheral
|
28.0%
28/100
|
31.4%
32/102
|
|
Infections and infestations
Cytomegalovirus infection
|
8.0%
8/100
|
4.9%
5/102
|
|
Infections and infestations
Gastroenteritis
|
6.0%
6/100
|
5.9%
6/102
|
|
Infections and infestations
Herpes zoster
|
7.0%
7/100
|
2.0%
2/102
|
|
Infections and infestations
Nasopharyngitis
|
21.0%
21/100
|
15.7%
16/102
|
|
Infections and infestations
Oral fungal infection
|
1.0%
1/100
|
5.9%
6/102
|
|
Infections and infestations
Pneumonia
|
6.0%
6/100
|
8.8%
9/102
|
|
Infections and infestations
Upper respiratory tract infection
|
7.0%
7/100
|
5.9%
6/102
|
|
Infections and infestations
Urinary tract infection
|
31.0%
31/100
|
29.4%
30/102
|
|
Injury, poisoning and procedural complications
Wound
|
2.0%
2/100
|
5.9%
6/102
|
|
Investigations
Blood creatinine increased
|
13.0%
13/100
|
4.9%
5/102
|
|
Investigations
Polyomavirus test positive
|
9.0%
9/100
|
9.8%
10/102
|
|
Metabolism and nutrition disorders
Gout
|
11.0%
11/100
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.0%
5/100
|
10.8%
11/102
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.0%
5/100
|
0.98%
1/102
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
12.0%
12/100
|
16.7%
17/102
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
2/100
|
7.8%
8/102
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.0%
11/100
|
5.9%
6/102
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.0%
5/100
|
9.8%
10/102
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
3.0%
3/100
|
8.8%
9/102
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.0%
4/100
|
5.9%
6/102
|
|
Nervous system disorders
Dizziness
|
8.0%
8/100
|
0.98%
1/102
|
|
Nervous system disorders
Headache
|
6.0%
6/100
|
7.8%
8/102
|
|
Psychiatric disorders
Depression
|
8.0%
8/100
|
2.9%
3/102
|
|
Renal and urinary disorders
Proteinuria
|
4.0%
4/100
|
13.7%
14/102
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
2.0%
2/100
|
5.9%
6/102
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.0%
7/100
|
9.8%
10/102
|
|
Skin and subcutaneous tissue disorders
Acne
|
2.0%
2/100
|
13.7%
14/102
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
5.0%
5/100
|
0.00%
0/102
|
|
Skin and subcutaneous tissue disorders
Hirsutism
|
8.0%
8/100
|
0.98%
1/102
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
5/100
|
9.8%
10/102
|
|
Vascular disorders
Lymphocele
|
5.0%
5/100
|
2.9%
3/102
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER