Trial Outcomes & Findings for 24 Months Follow-up, Two Arm Study to Compare the Cardiovascular Profile in a Regimen With Everolimus + Mycophenolic Acid (MPA) Versus (vs.) a Regimen of CNI+MPA in Maintenance Renal Transplant Recipients (NCT NCT01169701)
NCT ID: NCT01169701
Last Updated: 2015-12-07
Results Overview
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.
COMPLETED
PHASE4
71 participants
Baseline, Month 24
2015-12-07
Participant Flow
Participant milestones
| Measure |
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).
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
36
|
35
|
|
Overall Study
Safety Set
|
36
|
35
|
|
Overall Study
Intent to Treat (ITT) Set
|
32
|
28
|
|
Overall Study
COMPLETED
|
31
|
25
|
|
Overall Study
NOT COMPLETED
|
5
|
10
|
Reasons for withdrawal
| Measure |
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).
|
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.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Exclusion criteria
|
2
|
0
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Administrative problems
|
0
|
1
|
|
Overall Study
Serious adverse event
|
0
|
1
|
|
Overall Study
Sponsor decision
|
0
|
1
|
Baseline Characteristics
24 Months Follow-up, Two Arm Study to Compare the Cardiovascular Profile in a Regimen With Everolimus + Mycophenolic Acid (MPA) Versus (vs.) a Regimen of CNI+MPA in Maintenance Renal Transplant Recipients
Baseline characteristics by cohort
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
Total
n=71 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.1 Years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
47.4 Years
STANDARD_DEVIATION 13.2 • n=7 Participants
|
48.3 Years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Month 24Population: 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.
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.
Outcome measures
| Measure |
Tacrolimus
n=31 Participants
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).
|
Everolimus
n=25 Participants
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.
|
|---|---|---|
|
Change From Baseline in Left Ventricular Mass Index (LVMI)
|
-6.071 g/m^2.7
Standard Deviation 20.116
|
-4.008 g/m^2.7
Standard Deviation 17.610
|
SECONDARY outcome
Timeframe: Baseline, Month 6, month 12, month 24Population: 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.
Blood pressure was measured using ambulatory blood pressure monitoring (ABPM). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=31 Participants
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).
|
Everolimus
n=30 Participants
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.
|
|---|---|---|
|
Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure
Month 6 (n=31,29)
|
-0.6 mmHg
Standard Deviation 9.1
|
3.2 mmHg
Standard Deviation 8.6
|
|
Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure
Month 12 (n=28,24)
|
2.1 mmHg
Standard Deviation 6.9
|
2.7 mmHg
Standard Deviation 10.4
|
|
Change From Baseline in Mean 24 Hour Systolic and Diastolic Blood Pressure
Month 24 (n=29,24)
|
2.2 mmHg
Standard Deviation 10.6
|
2.0 mmHg
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: Month 6, month 24Population: 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.
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.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
Pulse Wave Velocity (PWV)
Month 6 (n=31,30)
|
7.01 m/sec
Standard Deviation 1.62
|
7.40 m/sec
Standard Deviation 1.62
|
|
Pulse Wave Velocity (PWV)
Month 24 (n=28,25)
|
7.58 m/sec
Standard Deviation 1.68
|
7.06 m/sec
Standard Deviation 1.74
|
SECONDARY outcome
Timeframe: Month 24Population: 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.
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.
Outcome measures
| Measure |
Tacrolimus
n=32 Participants
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).
|
Everolimus
n=28 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Major Cardiovascular Events (MACE)
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
SECONDARY outcome
Timeframe: Month 6, month 12, month 24Population: 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.
Serum samples were collected to analyze serum creatinine.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
Renal Function Measured by Serum Creatinine
Month 6 (n=33,29)
|
1.232 mg/dl
Standard Deviation 0.272
|
1.234 mg/dl
Standard Deviation 0.360
|
|
Renal Function Measured by Serum Creatinine
Month 12 (n=32,28)
|
1.231 mg/dl
Standard Deviation 0.278
|
1.256 mg/dl
Standard Deviation 0.367
|
|
Renal Function Measured by Serum Creatinine
Month 24 (n= 31,26)
|
1.217 mg/dl
Standard Deviation 0.235
|
1.260 mg/dl
Standard Deviation 0.358
|
SECONDARY outcome
Timeframe: Month 6, month 12, month 24Population: 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.
Creatinine clearance was calculated using the Cockroft-Gault formula.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
Renal Function as Measured by Creatinine Clearance
Month 6 (n=29,25)
|
64.841 mg/min
Standard Deviation 16.163
|
76.618 mg/min
Standard Deviation 27.708
|
|
Renal Function as Measured by Creatinine Clearance
Month 12 (n=28,25)
|
65.037 mg/min
Standard Deviation 15.866
|
73.363 mg/min
Standard Deviation 25.989
|
|
Renal Function as Measured by Creatinine Clearance
Month 24 (n=28,24)
|
66.933 mg/min
Standard Deviation 13.264
|
72.910 mg/min
Standard Deviation 23.926
|
SECONDARY outcome
Timeframe: Month 6, month 12, month 24Population: 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.
Estimated GFR was caluclated using the modification of diet in renal disease (MDRD) formula.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
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
|
63.781 mL/min/1.73m^2
Standard Deviation 18.380
|
|
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
|
61.225 mL/min/1.73m^2
Standard Deviation 19.239
|
|
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
|
60.779 mL/min/1.73m^2
Standard Deviation 17.023
|
SECONDARY outcome
Timeframe: Baseline, month 6, month 24Population: 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.
Blood samples were collected to analyze Troponin I and collagen type 1 C-telopeptide (ICTP). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
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 0.010
|
-0.006 ng/ml
Standard Deviation 0.026
|
|
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
|
-0.007 ng/ml
Standard Deviation 0.018
|
|
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
|
-0.195 ng/ml
Standard Deviation 0.234
|
|
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
|
-0.125 ng/ml
Standard Deviation 0.323
|
SECONDARY outcome
Timeframe: Baseline, month 6, month 24Population: 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.
Blood samples were collected to analyze HbA1c. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c)
Month 6 (n=20,22)
|
0.015 Percentage of HbA1c
Standard Deviation 0.184
|
0.159 Percentage of HbA1c
Standard Deviation 0.346
|
|
Change From Baseline in the Cardiovascular Biomarker, Glycosylated Hemoglobin (HbA1c)
Month12 (n=22,20)
|
0.045 Percentage of HbA1c
Standard Deviation 0.237
|
0.185 Percentage of HbA1c
Standard Deviation 0.407
|
SECONDARY outcome
Timeframe: Baseline, month 6, month 24Population: 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.
Blood samples were collected to analyze MPO. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO)
Month 6 (n=27,30)
|
0.433 U/mL
Standard Deviation 2.189
|
-0.093 U/mL
Standard Deviation 1.158
|
|
Change From Baseline in the Cardiovascular Biomarker, Myeloperoxidase (MPO)
Month 24 (n=24,24)
|
-0.329 U/mL
Standard Deviation 0.280
|
-0.642 U/mL
Standard Deviation 0.972
|
SECONDARY outcome
Timeframe: Baseline, month 6, month 24Population: 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.
Blood samples were collected to analyze NT-proBNP. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
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
|
-79.10 pg/mL
Standard Deviation 401.44
|
|
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
|
-193.3 pg/mL
Standard Deviation 590.90
|
SECONDARY outcome
Timeframe: Baseline, month 6, month 24Population: 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.
Blood samples were collected to analyze PCR. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
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 34.110
|
-33.36 ug/l
Standard Deviation 33.227
|
|
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
|
-28.17 ug/l
Standard Deviation 30.381
|
SECONDARY outcome
Timeframe: Baseline, month 6, month 24Population: 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.
Blood samples were collected to analyze CRP. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Tacrolimus
n=36 Participants
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).
|
Everolimus
n=35 Participants
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.
|
|---|---|---|
|
Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP)
Month 6 (n=27,30)
|
0.512 mg/dl
Standard Deviation 2.342
|
0.326 mg/dl
Standard Deviation 1.129
|
|
Change From Baseline in Cardiovascular Biomarkers, C-reactive Protein (CRP)
Month 24 (n=24,24)
|
0.100 mg/dl
Standard Deviation 0.469
|
-0.040 mg/dl
Standard Deviation 1.683
|
SECONDARY outcome
Timeframe: Month 24Population: 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.
The incidence of BPAR, graft loss, death and lost to follow-up events was calculated using relative frequency.
Outcome measures
| Measure |
Tacrolimus
n=32 Participants
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).
|
Everolimus
n=28 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up
BPAR
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up
Graft loss
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR), Graft Loss, Death and Lost to Follow up
Deaths
|
0.00 Percentage of participants
|
0.00 Percentage of participants
|
|
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
|
0.00 Percentage of participants
|
Adverse Events
Tacrolimus
Everolimus
Serious adverse events
| Measure |
Tacrolimus
n=36 participants at risk
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).
|
Everolimus
n=35 participants at risk
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.
|
|---|---|---|
|
General disorders
Pyrexia
|
2.8%
1/36
|
0.00%
0/35
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
Oral herpes
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
Pneumonia
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
Pyelonephritis
|
2.8%
1/36
|
0.00%
0/35
|
|
Infections and infestations
Respiratory syncytial virus infection
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
Septic shock
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
Urosepsis
|
0.00%
0/36
|
2.9%
1/35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
2.8%
1/36
|
0.00%
0/35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system lymphoma
|
2.8%
1/36
|
0.00%
0/35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.00%
0/36
|
2.9%
1/35
|
|
Nervous system disorders
Cerebrovascular accident
|
2.8%
1/36
|
0.00%
0/35
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/36
|
2.9%
1/35
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/36
|
2.9%
1/35
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/36
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.8%
1/36
|
2.9%
1/35
|
|
Surgical and medical procedures
Arteriovenous fistula operation
|
0.00%
0/36
|
2.9%
1/35
|
Other adverse events
| Measure |
Tacrolimus
n=36 participants at risk
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).
|
Everolimus
n=35 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/36
|
8.6%
3/35
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/36
|
5.7%
2/35
|
|
Blood and lymphatic system disorders
Polycythaemia
|
2.8%
1/36
|
5.7%
2/35
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/36
|
8.6%
3/35
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
4/36
|
8.6%
3/35
|
|
General disorders
Asthenia
|
5.6%
2/36
|
0.00%
0/35
|
|
General disorders
Oedema peripheral
|
8.3%
3/36
|
17.1%
6/35
|
|
Infections and infestations
Bronchitis
|
5.6%
2/36
|
0.00%
0/35
|
|
Infections and infestations
Escherichia urinary tract infection
|
11.1%
4/36
|
11.4%
4/35
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/36
|
5.7%
2/35
|
|
Infections and infestations
Pneumonia
|
0.00%
0/36
|
5.7%
2/35
|
|
Infections and infestations
Respiratory tract infection
|
2.8%
1/36
|
5.7%
2/35
|
|
Infections and infestations
Urinary tract infection
|
19.4%
7/36
|
2.9%
1/35
|
|
Infections and infestations
Urinary tract infection bacterial
|
2.8%
1/36
|
5.7%
2/35
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
0.00%
0/36
|
5.7%
2/35
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
5.6%
2/36
|
2.9%
1/35
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
8.3%
3/36
|
2.9%
1/35
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
2.8%
1/36
|
5.7%
2/35
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.6%
2/36
|
5.7%
2/35
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/36
|
5.7%
2/35
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
5.6%
2/36
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
5.6%
2/36
|
0.00%
0/35
|
|
Nervous system disorders
Dizziness
|
0.00%
0/36
|
5.7%
2/35
|
|
Nervous system disorders
Headache
|
5.6%
2/36
|
5.7%
2/35
|
|
Psychiatric disorders
Depression
|
0.00%
0/36
|
5.7%
2/35
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/36
|
14.3%
5/35
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
5.6%
2/36
|
0.00%
0/35
|
|
Vascular disorders
Hypertension
|
2.8%
1/36
|
14.3%
5/35
|
Additional Information
Study Director
Novartis Pharmaceuticals
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