Trial Outcomes & Findings for Efficacy and Safety of Everolimus in Combination With Cyclosporine Microemulsion Versus Everolimus in Combination With Enteric-coated Mycophenolate Sodium (EC-MPS), in Adult Renal Transplant Patients in Maintenance. (NCT NCT00425308)
NCT ID: NCT00425308
Last Updated: 2017-03-30
Results Overview
Primary efficacy endpoint: between treatment analysis of change in iohexol plasmatic clearance (mL/min) from baseline to Month 12 (M12)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
30 participants
Primary outcome timeframe
From Baseline to Month 12
Results posted on
2017-03-30
Participant Flow
This is a prospective, national, multicenter, randomized, open label study, 12 months duration. Ten centers have been included with a study start October 2006 and end date May 2009.
Participant milestones
| Measure |
Cyclosporine
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
11
|
14
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
Cyclosporine
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Death
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Everolimus in Combination With Cyclosporine Microemulsion Versus Everolimus in Combination With Enteric-coated Mycophenolate Sodium (EC-MPS), in Adult Renal Transplant Patients in Maintenance.
Baseline characteristics by cohort
| Measure |
Cyclosporine
n=15 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=15 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.3 years
STANDARD_DEVIATION 9.46 • n=5 Participants
|
58.8 years
STANDARD_DEVIATION 7.55 • n=7 Participants
|
60.6 years
STANDARD_DEVIATION 8.60 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline to Month 12Population: Intent to Treat (ITT) Population: all patients with a baseline value
Primary efficacy endpoint: between treatment analysis of change in iohexol plasmatic clearance (mL/min) from baseline to Month 12 (M12)
Outcome measures
| Measure |
Cyclosporine
n=13 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=14 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Change in Glomerular Filtration Rate Estimated by Iohexol Plasma Clearance 12 Months After Randomization Between the 2 Groups of Patients.
|
-4.07 (mL/min)
Standard Error 5.03
|
10.30 (mL/min)
Standard Error 4.84
|
PRIMARY outcome
Timeframe: From Baseline to Month 12Population: Intent to Treat (ITT) Population: completed patients
Primary efficacy endpoint: between treatment analysis of change in iohexol plasmatic clearance (mL/min) from baseline to Month 12 (M12)
Outcome measures
| Measure |
Cyclosporine
n=8 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=13 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Change in the Glomerular Filtration Rate Estimated by Iohexol Plasma Clearance 12 Months After Randomization Between the 2 Groups of Patients Who Completed Trial
|
1.46 (mL/min)
Standard Error 6.60
|
12.00 (mL/min)
Standard Error 5.06
|
SECONDARY outcome
Timeframe: From Baseline to Month 3, 6, and 12Population: Intent to Treat Population
Outcome measures
| Measure |
Cyclosporine
n=13 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=14 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Change in Renal Function Assessed by Serum Creatinine at Month 3, Month 6 and Month 12
Baseline [N = 13; N = 14]
|
161.7 µmol/L
Standard Deviation 60.78
|
153.2 µmol/L
Standard Deviation 47.46
|
|
Change in Renal Function Assessed by Serum Creatinine at Month 3, Month 6 and Month 12
Month 3 [N = 12; N = 14]
|
156.6 µmol/L
Standard Deviation 51.41
|
138.9 µmol/L
Standard Deviation 40.85
|
|
Change in Renal Function Assessed by Serum Creatinine at Month 3, Month 6 and Month 12
Month 6 [N = 12; N = 13]
|
170.8 µmol/L
Standard Deviation 59.36
|
139.8 µmol/L
Standard Deviation 42.81
|
|
Change in Renal Function Assessed by Serum Creatinine at Month 3, Month 6 and Month 12
Month 12 [N = 13; N = 14]
|
227.7 µmol/L
Standard Deviation 144.0
|
130.4 µmol/L
Standard Deviation 40.27
|
SECONDARY outcome
Timeframe: Month 6 and 12Population: Intent to Treat Population
Outcome measures
| Measure |
Cyclosporine
n=13 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=14 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Number of Participants With Biopsy-proven Acute Rejection (BPAR) at Month 6 and Month 12.
Yes: treatment failure Month 6
|
0 participants
|
0 participants
|
|
Number of Participants With Biopsy-proven Acute Rejection (BPAR) at Month 6 and Month 12.
No: treatment failure Month 6
|
0 participants
|
0 participants
|
|
Number of Participants With Biopsy-proven Acute Rejection (BPAR) at Month 6 and Month 12.
Yes: treatment failure Month 12
|
1 participants
|
0 participants
|
|
Number of Participants With Biopsy-proven Acute Rejection (BPAR) at Month 6 and Month 12.
No: treatment failure Month 12
|
12 participants
|
14 participants
|
SECONDARY outcome
Timeframe: Month 12Population: Intent to Treat (ITT) Population
Outcome measures
| Measure |
Cyclosporine
n=13 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=14 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Number of Participants With Treatment Failures Assessed by Biopsy-proven Acute Rejection (BPAR), Graft Loss/Re-transplantation, Death or Lost to Follow-up at Month 12.
BPAR 12 months
|
1 participants
|
0 participants
|
|
Number of Participants With Treatment Failures Assessed by Biopsy-proven Acute Rejection (BPAR), Graft Loss/Re-transplantation, Death or Lost to Follow-up at Month 12.
Graft Loss 12 months
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment Failures Assessed by Biopsy-proven Acute Rejection (BPAR), Graft Loss/Re-transplantation, Death or Lost to Follow-up at Month 12.
Death 12 months
|
1 participants
|
0 participants
|
|
Number of Participants With Treatment Failures Assessed by Biopsy-proven Acute Rejection (BPAR), Graft Loss/Re-transplantation, Death or Lost to Follow-up at Month 12.
Lost to Follow-up 12 months
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From Baseline to Month 3, 6, and 12Population: Intent to Treat Population
Change in creatinine clearance, Nankivell formula (mL/min/1.73m²) from baseline to M12
Outcome measures
| Measure |
Cyclosporine
n=13 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=14 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Change in Renal Function Assessed by Creatinine Clearance at Month 3, Month 6 and Month 12
Baseline [N = 12; N = 13]
|
56.3 mL/min/1.73m²
Standard Deviation 20.07
|
60.3 mL/min/1.73m²
Standard Deviation 18.49
|
|
Change in Renal Function Assessed by Creatinine Clearance at Month 3, Month 6 and Month 12
Month 3 [N = 10; N = 14]
|
57.3 mL/min/1.73m²
Standard Deviation 19.49
|
67.1 mL/min/1.73m²
Standard Deviation 19.24
|
|
Change in Renal Function Assessed by Creatinine Clearance at Month 3, Month 6 and Month 12
Month 6 [N = 10; N = 12]
|
50.3 mL/min/1.73m²
Standard Deviation 15.98
|
68.1 mL/min/1.73m²
Standard Deviation 18.25
|
|
Change in Renal Function Assessed by Creatinine Clearance at Month 3, Month 6 and Month 12
Month 12 [N = 7; N = 11]
|
48.7 mL/min/1.73m²
Standard Deviation 24.70
|
70.1 mL/min/1.73m²
Standard Deviation 18.34
|
SECONDARY outcome
Timeframe: From Baseline to Month 3, 6, and 12Population: Intent to Treat Population
Change in proteinuria (g/24h) from baseline to M12
Outcome measures
| Measure |
Cyclosporine
n=13 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=14 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Change in Renal Function Assessed by Proteinuria at Month 3, Month 6 and Month 12
Baseline [N = 9; N = 10]
|
0.44 g/24h
Standard Deviation 0.447
|
0.47 g/24h
Standard Deviation 0.390
|
|
Change in Renal Function Assessed by Proteinuria at Month 3, Month 6 and Month 12
Month 3 [N = 9; N = 8]
|
0.53 g/24h
Standard Deviation 0.248
|
0.24 g/24h
Standard Deviation 0.267
|
|
Change in Renal Function Assessed by Proteinuria at Month 3, Month 6 and Month 12
Month 6 [N = 6; N = 5]
|
0.44 g/24h
Standard Deviation 0.335
|
0.33 g/24h
Standard Deviation 0.262
|
|
Change in Renal Function Assessed by Proteinuria at Month 3, Month 6 and Month 12
Month 12 [N = 7; N = 10]
|
0.48 g/24h
Standard Deviation 0.537
|
0.75 g/24h
Standard Deviation 0.732
|
SECONDARY outcome
Timeframe: From Baseline to Month 1, 3, 6, 9, and 12Population: Safety population
Blood chemistry - fasting glycemia (mmol/L)
Outcome measures
| Measure |
Cyclosporine
n=15 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=15 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Assessing Cardiovascular Risk Factors Based on Fasting Glucose.
Baseline [N = 15; N = 15]
|
5.5 mmol/L
Standard Deviation 0.97
|
5.2 mmol/L
Standard Deviation 0.47
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Glucose.
Month 1 [N = 15; N = 15]
|
5.2 mmol/L
Standard Deviation 0.90
|
5.3 mmol/L
Standard Deviation 0.95
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Glucose.
Month 3 [N = 14; N = 15]
|
5.6 mmol/L
Standard Deviation 1.26
|
5.2 mmol/L
Standard Deviation 1.26
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Glucose.
Month 6 [N = 14; N = 14]
|
5.5 mmol/L
Standard Deviation 1.15
|
5.1 mmol/L
Standard Deviation 1.06
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Glucose.
Month 9 [N = 12; N = 13]
|
5.3 mmol/L
Standard Deviation 1.04
|
5.6 mmol/L
Standard Deviation 1.60
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Glucose.
Month 12 [N = 14; N = 13]
|
4.8 mmol/L
Standard Deviation 0.94
|
5.4 mmol/L
Standard Deviation 1.21
|
SECONDARY outcome
Timeframe: From Baseline to Month 1, 3, 6, 9, and 12Population: Safety population
Blood chemistry - total cholesterol (mmol/L)
Outcome measures
| Measure |
Cyclosporine
n=15 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=15 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol.
Baseline [N = 13; N = 14]
|
5.7 mmol/L
Standard Deviation 1.42
|
6.0 mmol/L
Standard Deviation 2.26
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol.
Month 1 [N = 11; N = 14]
|
5.0 mmol/L
Standard Deviation 1.20
|
5.7 mmol/L
Standard Deviation 0.76
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol.
Month 3 [N = 13; N = 14]
|
5.3 mmol/L
Standard Deviation 1.77
|
5.6 mmol/L
Standard Deviation 1.43
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol.
Month 6 [N = 12; N = 12]
|
5.5 mmol/L
Standard Deviation 1.60
|
5.7 mmol/L
Standard Deviation 1.78
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol.
Month 9 [N = 9; N = 12]
|
5.4 mmol/L
Standard Deviation 1.49
|
5.4 mmol/L
Standard Deviation 1.31
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Total Cholesterol.
Month 12 [N = 12; N = 11]
|
5.6 mmol/L
Standard Deviation 1.61
|
5.8 mmol/L
Standard Deviation 0.60
|
SECONDARY outcome
Timeframe: From Baseline to Month 3, 6, and 12Population: Safety population
Outcome measures
| Measure |
Cyclosporine
n=15 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=15 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Baseline LDL [N = 10; N = 14]
|
3.4 mmol/L
Standard Deviation 0.89
|
3.1 mmol/L
Standard Deviation 0.84
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Baseline HDL [N = 10; N = 14]
|
1.5 mmol/L
Standard Deviation 0.54
|
1.5 mmol/L
Standard Deviation 0.51
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Month 3 LDL [N = 12; N = 14]
|
3.2 mmol/L
Standard Deviation 0.89
|
3.4 mmol/L
Standard Deviation 0.97
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Month 3 HDL [N = 12; N = 13]
|
1.7 mmol/L
Standard Deviation 0.75
|
1.5 mmol/L
Standard Deviation 0.37
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Month 6 LDL [N = 12; N = 12]
|
3.2 mmol/L
Standard Deviation 1.15
|
3.3 mmol/L
Standard Deviation 1.48
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Month 6 HDL [N = 12; N = 12]
|
1.6 mmol/L
Standard Deviation 0.47
|
1.4 mmol/L
Standard Deviation 0.50
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Month 12 LDL [N = 10; N = 11]
|
3.0 mmol/L
Standard Deviation 0.84
|
3.2 mmol/L
Standard Deviation 0.65
|
|
Assessing Cardiovascular Risk Factors Based on Fasting High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol.
Month 12 HDL [N = 10; N = 11]
|
1.7 mmol/L
Standard Deviation 0.74
|
1.5 mmol/L
Standard Deviation 0.52
|
SECONDARY outcome
Timeframe: From Baseline to Month 1, 3, 6, 9, and 12Population: Safety population
Outcome measures
| Measure |
Cyclosporine
n=15 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=15 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides.
Baseline [N = 11; N = 14]
|
2.4 mmol/L
Standard Deviation 1.43
|
1.8 mmol/L
Standard Deviation 0.93
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides.
Month 1 [N = 10; N = 14]
|
2.1 mmol/L
Standard Deviation 1.16
|
2.0 mmol/L
Standard Deviation 0.81
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides.
Month 3 [N = 13; N = 14]
|
2.0 mmol/L
Standard Deviation 0.78
|
2.2 mmol/L
Standard Deviation 0.78
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides.
Month 6 [N = 12; N = 12]
|
1.9 mmol/L
Standard Deviation 0.51
|
2.1 mmol/L
Standard Deviation 0.68
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides.
Month 9 [N = 10; N = 12]
|
1.9 mmol/L
Standard Deviation 0.77
|
2.2 mmol/L
Standard Deviation 0.94
|
|
Assessing Cardiovascular Risk Factors Based on Fasting Triglycerides.
Month 12 [N = 12; N = 11]
|
2.3 mmol/L
Standard Deviation 1.05
|
2.3 mmol/L
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: From Baseline to Month 3, 6, and 12Population: Safety population
Blood chemistry - C-reactive Protein (CRP) (mg/L)
Outcome measures
| Measure |
Cyclosporine
n=15 Participants
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-coated Mycophenolate Sodium (EC-MPS)
n=15 Participants
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Assessing Cardiovascular Risk Factors Based on Fasting C-reactive Protein (CRP).
Baseline [N = 13; N = 14]
|
11.4 mg/L
Standard Deviation 17.83
|
3.0 mg/L
Standard Deviation 2.45
|
|
Assessing Cardiovascular Risk Factors Based on Fasting C-reactive Protein (CRP).
Month 3 [N = 11; N = 11]
|
6.3 mg/L
Standard Deviation 4.88
|
10.3 mg/L
Standard Deviation 16.27
|
|
Assessing Cardiovascular Risk Factors Based on Fasting C-reactive Protein (CRP).
Month 6 [N = 11; N = 9]
|
8.0 mg/L
Standard Deviation 8.24
|
5.6 mg/L
Standard Deviation 5.75
|
|
Assessing Cardiovascular Risk Factors Based on Fasting C-reactive Protein (CRP).
Month 12 [N = 14; N = 12]
|
34.2 mg/L
Standard Deviation 62.92
|
12.6 mg/L
Standard Deviation 27.23
|
Adverse Events
Cyclosporine
Serious events: 8 serious events
Other events: 11 other events
Deaths: 0 deaths
Enteric-Coated Mycophenolate Sodium (EC-MPS)
Serious events: 10 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cyclosporine
n=15 participants at risk
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-Coated Mycophenolate Sodium (EC-MPS)
n=15 participants at risk
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/15
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/15
|
6.7%
1/15
|
|
Cardiac disorders
Cardio-respiratory arrest
|
6.7%
1/15
|
0.00%
0/15
|
|
Cardiac disorders
Myocardial infarction
|
6.7%
1/15
|
0.00%
0/15
|
|
Ear and labyrinth disorders
Acute vestibular syndrome
|
0.00%
0/15
|
6.7%
1/15
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/15
|
6.7%
1/15
|
|
General disorders
Chills
|
0.00%
0/15
|
6.7%
1/15
|
|
General disorders
Oedema peripheral
|
0.00%
0/15
|
6.7%
1/15
|
|
General disorders
Pyrexia
|
0.00%
0/15
|
13.3%
2/15
|
|
Hepatobiliary disorders
Cholecystitis acute
|
6.7%
1/15
|
0.00%
0/15
|
|
Immune system disorders
Kidney transplant rejection
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Bronchitis
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Cellulitis
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Gangrene
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Herpes zoster ophthalmic
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Liver abscess
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Localised infection
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Pneumonia
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Pyelonephritis
|
6.7%
1/15
|
6.7%
1/15
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/15
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Fall
|
13.3%
2/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Wound evisceration
|
0.00%
0/15
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
6.7%
1/15
|
0.00%
0/15
|
|
Investigations
Blood creatinine increased
|
0.00%
0/15
|
13.3%
2/15
|
|
Investigations
C-reactive protein increased
|
0.00%
0/15
|
6.7%
1/15
|
|
Investigations
Prostatic specific antigen increased
|
0.00%
0/15
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
6.7%
1/15
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/15
|
6.7%
1/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma
|
6.7%
1/15
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/15
|
6.7%
1/15
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15
|
0.00%
0/15
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/15
|
6.7%
1/15
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/15
|
6.7%
1/15
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.00%
0/15
|
6.7%
1/15
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/15
|
6.7%
1/15
|
|
Renal and urinary disorders
Renal failure acute
|
6.7%
1/15
|
0.00%
0/15
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.00%
0/15
|
6.7%
1/15
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/15
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
6.7%
1/15
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/15
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/15
|
6.7%
1/15
|
|
Surgical and medical procedures
Cholecystectomy
|
6.7%
1/15
|
0.00%
0/15
|
|
Vascular disorders
Orthostatic hypotension
|
6.7%
1/15
|
0.00%
0/15
|
Other adverse events
| Measure |
Cyclosporine
n=15 participants at risk
Control Arm: Everolimus dose has been adjusted to reach in Group 1, assessment of everolimus dose/trough level (C0), between 3 and 8 ng/ml plus Cyclosporine in which Group 1 dose adjusted to reach, assessment of Cyclosporine dosage and blood concentration (C2), between 200 and 450 ng/ml plus steroids
|
Enteric-Coated Mycophenolate Sodium (EC-MPS)
n=15 participants at risk
Everolimus dose has been adjusted to reach in Group 2, assessment of everolimus dose/trough level (C0), between 6 and 10 ng/ml plus Enteric-Coated Mycophenolate Sodium (EC-MPS) 720 mg/d (360mg the morning and 360 mg the evening) plus steroids
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
3/15
|
13.3%
2/15
|
|
Endocrine disorders
Hyperparathyroidism
|
6.7%
1/15
|
0.00%
0/15
|
|
Endocrine disorders
Hyperthyroidism
|
6.7%
1/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/15
|
33.3%
5/15
|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
2/15
|
6.7%
1/15
|
|
Gastrointestinal disorders
Enteritis
|
6.7%
1/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Gingival hypertrophy
|
0.00%
0/15
|
6.7%
1/15
|
|
General disorders
Asthenia
|
6.7%
1/15
|
0.00%
0/15
|
|
General disorders
Chest pain
|
6.7%
1/15
|
6.7%
1/15
|
|
General disorders
Oedema
|
0.00%
0/15
|
6.7%
1/15
|
|
General disorders
Oedema peripheral
|
26.7%
4/15
|
26.7%
4/15
|
|
General disorders
Pyrexia
|
6.7%
1/15
|
6.7%
1/15
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/15
|
6.7%
1/15
|
|
Hepatobiliary disorders
Cytolytic hepatitis
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Alveolar osteitis
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Bronchitis
|
13.3%
2/15
|
6.7%
1/15
|
|
Infections and infestations
Ear infection
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Influenza
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Nasal abscess
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Pharyngitis
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Renal cyst infection
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Sinusitis
|
0.00%
0/15
|
6.7%
1/15
|
|
Infections and infestations
Urinary tract infection
|
20.0%
3/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Chronic allograft nephropathy
|
6.7%
1/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Therapeutic agent toxicity
|
6.7%
1/15
|
0.00%
0/15
|
|
Investigations
Blood creatinine increased
|
6.7%
1/15
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Dehydration
|
6.7%
1/15
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
20.0%
3/15
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
0.00%
0/15
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.7%
1/15
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/15
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Iron deficiency
|
0.00%
0/15
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/15
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
1/15
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/15
|
6.7%
1/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
0.00%
0/15
|
6.7%
1/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
6.7%
1/15
|
0.00%
0/15
|
|
Nervous system disorders
Cerebral venous thrombosis
|
0.00%
0/15
|
6.7%
1/15
|
|
Renal and urinary disorders
Microalbuminuria
|
0.00%
0/15
|
6.7%
1/15
|
|
Renal and urinary disorders
Nephropathy toxic
|
6.7%
1/15
|
0.00%
0/15
|
|
Renal and urinary disorders
Proteinuria
|
20.0%
3/15
|
0.00%
0/15
|
|
Renal and urinary disorders
Renal failure acute
|
13.3%
2/15
|
0.00%
0/15
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/15
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
6.7%
1/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/15
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Prurigo
|
0.00%
0/15
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.7%
1/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.00%
0/15
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/15
|
6.7%
1/15
|
|
Vascular disorders
Hypertension
|
20.0%
3/15
|
0.00%
0/15
|
|
Vascular disorders
Subclavian artery stenosis
|
6.7%
1/15
|
0.00%
0/15
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee Disclosure Restriction Description: 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.
- Publication restrictions are in place
Restriction type: OTHER