MedTrace Logo

Trial Outcomes & Findings for Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Calcineurin Inhibitor (CNI)-Free Regimen and a CNI-low Dose Regimen (NCT NCT00514514)

NCT ID: NCT00514514

Last Updated: 2017-01-18

Results Overview

Demonstrate superiority of CNI-Free vs Standard Regimen in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. P-values are not adjusted

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

802 participants

Primary outcome timeframe

From randomization at BL2 (Month 3) to Month 12 post-transplant

Results posted on

2017-01-18

Participant Flow

.817 patients were screened and 802 were enrolled on Day of transplant which served as Baseline Visit 1. For three months post transplantation, in the pre-phase period, all patients received induction therapy (Simulect®) and immunosuppressive therapy consisting of Myfortic, Sandimmun Optoral and corticosteroids.

At month 3 post transplant, Baseline Visit 2, additional eligibility was assessed and patients randomized to one of 3 treatment arms and stratified according to kidney donor (living or cadaveric).

Participant milestones

Participant milestones
Measure
Standard Regimen
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Pre-phase
STARTED
802
0
0
Pre-phase
COMPLETED
499
0
0
Pre-phase
NOT COMPLETED
303
0
0
Randomized - 9 Month
STARTED
166
171
162
Randomized - 9 Month
Randomized - Received Treatment
165
171
161
Randomized - 9 Month
COMPLETED
127
110
124
Randomized - 9 Month
NOT COMPLETED
39
61
38
Extension - 4 Years
STARTED
145
139
134
Extension - 4 Years
Non-randomized (Followed)
95
0
0
Extension - 4 Years
COMPLETED
108
117
113
Extension - 4 Years
NOT COMPLETED
37
22
21

Reasons for withdrawal

Reasons for withdrawal
Measure
Standard Regimen
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Pre-phase
Death
10
0
0
Pre-phase
administrative problems
2
0
0
Pre-phase
Protocol Violation
6
0
0
Pre-phase
condition no longer requires study drug
7
0
0
Pre-phase
abnormal test procedure results
15
0
0
Pre-phase
Lost to Follow-up
2
0
0
Pre-phase
abnormal lab values
23
0
0
Pre-phase
Lack of Efficacy
35
0
0
Pre-phase
Adverse Event
137
0
0
Pre-phase
Withdrawal by Subject
66
0
0
Randomized - 9 Month
Death
3
2
2
Randomized - 9 Month
Administrative problems
1
1
2
Randomized - 9 Month
Withdrawal by Subject
7
7
5
Randomized - 9 Month
Protocol Violation
1
1
0
Randomized - 9 Month
Lack of Efficacy
2
3
1
Randomized - 9 Month
Abnormal laboratory values
0
3
1
Randomized - 9 Month
Adverse Event
25
44
27
Extension - 4 Years
Withdrawal by Subject
5
2
2
Extension - 4 Years
Lost to Follow-up
12
10
9
Extension - 4 Years
Administrative problems
3
1
1
Extension - 4 Years
Death
8
3
6
Extension - 4 Years
Adverse Event
9
6
3

Baseline Characteristics

Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Calcineurin Inhibitor (CNI)-Free Regimen and a CNI-low Dose Regimen

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Standard Regimen
n=165 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=171 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=161 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Total
n=497 Participants
Total of all reporting groups
Age, Continuous
49.9 years
STANDARD_DEVIATION 11.8 • n=99 Participants
48.9 years
STANDARD_DEVIATION 12.5 • n=107 Participants
48.6 years
STANDARD_DEVIATION 12.3 • n=206 Participants
49.1 years
STANDARD_DEVIATION 12.2 • n=7 Participants
Gender
Female
65 Participants
n=99 Participants
69 Participants
n=107 Participants
61 Participants
n=206 Participants
195 Participants
n=7 Participants
Gender
Male
100 Participants
n=99 Participants
102 Participants
n=107 Participants
100 Participants
n=206 Participants
302 Participants
n=7 Participants

PRIMARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 12 post-transplant

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization.

Demonstrate superiority of CNI-Free vs Standard Regimen in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. P-values are not adjusted

Outcome measures

Outcome measures
Measure
Standard Regimen
n=159 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=163 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=160 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR Via Nankivell Method at Month 12 - CNI-Free vs Standard Regimen
63.03 ml/min/1.73m²
Interval 60.57 to 65.49
68.59 ml/min/1.73m²
Interval 66.1 to 71.08
63.08 ml/min/1.73m²
Interval 60.62 to 65.55

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 12 post-transplant

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization.

Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.

Outcome measures

Outcome measures
Measure
Standard Regimen
n=159 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=163 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=160 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR Via Nankivell Formula at Month 12 - All Regimens
63.03 ml/min/1.73m²
Interval 60.57 to 65.49
68.59 ml/min/1.73m²
Interval 66.1 to 71.08
63.08 ml/min/1.73m²
Interval 60.62 to 65.55

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 12 post-transplant

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization.

Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.

Outcome measures

Outcome measures
Measure
Standard Regimen
n=151 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=158 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=157 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR at Month 12 Utilizing Modification of Diet in Renal Disease (MDRD) Method
50.23 ml/min/1.73m²
Interval 47.66 to 52.8
56.36 ml/min/1.73m²
Interval 53.77 to 58.94
50.24 ml/min/1.73m²
Interval 47.7 to 52.77

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 12 post-transplant

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization.

Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

Outcome measures

Outcome measures
Measure
Standard Regimen
n=160 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=164 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=160 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR at Month 12 Utilizing Cockcroft-Gault Formula
60.18 ml/min/1.73m²
Interval 57.33 to 63.03
64.87 ml/min/1.73m²
Interval 61.99 to 67.75
61.16 ml/min/1.73m²
Interval 58.31 to 64.02

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 12 post-transplant

Population: Participants analyzed required at least one post randomization value. ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization

Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

Outcome measures

Outcome measures
Measure
Standard Regimen
n=160 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=165 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=160 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Mean Change in Serum Creatinine From Month 3 to Month 12
1.66 mg/dl
Interval 1.51 to 1.81
1.58 mg/dl
Interval 1.43 to 1.73
1.76 mg/dl
Interval 1.61 to 1.91

SECONDARY outcome

Timeframe: From Baseline 2 (Month 3) to Month 6

Population: The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization.

Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).

Outcome measures

Outcome measures
Measure
Standard Regimen
n=165 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=171 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=161 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
BPAR
6 Participants
Interval 1.51 to 1.81
15 Participants
Interval 1.43 to 1.73
10 Participants
Interval 1.61 to 1.91
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
Graft loss
0 Participants
1 Participants
1 Participants
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
Death
1 Participants
1 Participants
0 Participants
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
Lost to follow-up
0 Participants
0 Participants
0 Participants
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
Discontinuation due to lack of efficacy
1 Participants
2 Participants
1 Participants
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
Discontinuation due to adverse event
8 Participants
26 Participants
13 Participants
Efficacy Event Data From Baseline 2 (Month 3) to Month 6
Therapy failure composite
14 Participants
37 Participants
19 Participants

SECONDARY outcome

Timeframe: From Baseline 2 (Month 3) to Month 12

Population: The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization.

Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).

Outcome measures

Outcome measures
Measure
Standard Regimen
n=165 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=171 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=161 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Efficacy Event Data Baseline 2 (Month 3) to Month 12
BPAR
13 Participants
Interval 1.51 to 1.81
20 Participants
Interval 1.43 to 1.73
13 Participants
Interval 1.61 to 1.91
Efficacy Event Data Baseline 2 (Month 3) to Month 12
Graft loss
1 Participants
2 Participants
1 Participants
Efficacy Event Data Baseline 2 (Month 3) to Month 12
Death
3 Participants
2 Participants
2 Participants
Efficacy Event Data Baseline 2 (Month 3) to Month 12
Lost to follow-up
0 Participants
0 Participants
0 Participants
Efficacy Event Data Baseline 2 (Month 3) to Month 12
Discontinuation due to lack of efficacy
2 Participants
3 Participants
1 Participants
Efficacy Event Data Baseline 2 (Month 3) to Month 12
Discontinuation due to adverse event
25 Participants
44 Participants
27 Participants
Efficacy Event Data Baseline 2 (Month 3) to Month 12
Therapy failure composite
34 Participants
58 Participants
35 Participants

SECONDARY outcome

Timeframe: From Baseline 2 (Month 3) to Month 12

Population: The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization.

The Framingham Score (based on LDL cholesterol level) estimates the coronary heart disease risk (%) of developing one of the following coronary heart diseases: angina pectoris, myocardial infarction, or coronary disease death, over the course of 10 years.

Outcome measures

Outcome measures
Measure
Standard Regimen
n=165 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=171 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=161 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk)
Change from Baseline 2 to Month 12 (n=158,166,156)
-0.7 Percent risk
Standard Deviation 5.8
0.4 Percent risk
Standard Deviation 5.1
-0.7 Percent risk
Standard Deviation 5.4
Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk)
Baseline 1/Visit 1 (n=165,171,161)
10.9 Percent risk
Standard Deviation 8 • Interval 1.51 to 1.81
10.2 Percent risk
Standard Deviation 7.4 • Interval 1.43 to 1.73
9.5 Percent risk
Standard Deviation 6.9 • Interval 1.61 to 1.91
Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk)
Baseline 2/Month 3 (n=165,171,161)
10.3 Percent risk
Standard Deviation 7.7
8.8 Percent risk
Standard Deviation 5.9
9.3 Percent risk
Standard Deviation 7.2
Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk)
Month 12 (n=158,166,156)
9.4 Percent risk
Standard Deviation 6.8
9.1 Percent risk
Standard Deviation 6.4
8.7 Percent risk
Standard Deviation 6.8

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 60

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization

Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.

Outcome measures

Outcome measures
Measure
Standard Regimen
n=99 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=108 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=104 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR Calculated Via Nankivell Formula at Month 60
60.24 ml/min/1.73m²
Interval 57.11 to 63.38
66.98 ml/min/1.73m²
Interval 63.78 to 70.17
58.74 ml/min/1.73m²
Interval 55.58 to 61.9

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 60 post-transplant

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization

Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl) For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

Outcome measures

Outcome measures
Measure
Standard Regimen
n=162 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=165 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=159 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR at Month 60 Utilizing Cockcroft-Gault Formula
55.92 ml/min/1.73m²
Interval 52.36 to 59.48
61.6 ml/min/1.73m²
Interval 57.99 to 65.2
52.91 ml/min/1.73m²
Interval 49.32 to 56.5

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 60 post-transplant

Population: Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization

Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.

Outcome measures

Outcome measures
Measure
Standard Regimen
n=152 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=159 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=156 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
GFR at Month 60 Utilizing Modification of Diet in Renal Disease (MDRD) Method
47.56 ml/min/1.73m²
Interval 44.58 to 50.54
53.41 ml/min/1.73m²
Interval 50.4 to 56.42
44.79 ml/min/1.73m²
Interval 41.83 to 47.74

SECONDARY outcome

Timeframe: From randomization at BL2 (Month 3) to Month 60 post-transplant

Population: Participants analyzed were previously enrolled in the core study and had at least one serum creatinine value in the extension period.

Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

Outcome measures

Outcome measures
Measure
Standard Regimen
n=82 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=49 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=28 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Mean Change in Serum Creatinine From Month 3 to Month 60
1.94 mg/dl
Interval 1.72 to 2.15
1.69 mg/dl
Interval 1.47 to 1.91
2.01 mg/dl
Interval 1.79 to 2.23

SECONDARY outcome

Timeframe: Events starting after Month 12

Population: The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization.

Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).

Outcome measures

Outcome measures
Measure
Standard Regimen
n=165 Participants
Myfortic, Sandimmun Optoral and corticosteroids
CNI Free Regimen
n=171 Participants
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids
CNI Low Regimen
n=161 Participants
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Efficacy Event Data After Month 12 to Month 60
BPAR
13 Participants
Interval 1.51 to 1.81
13 Participants
Interval 1.43 to 1.73
12 Participants
Interval 1.61 to 1.91
Efficacy Event Data After Month 12 to Month 60
Graft loss
7 Participants
7 Participants
3 Participants
Efficacy Event Data After Month 12 to Month 60
Death
7 Participants
4 Participants
9 Participants
Efficacy Event Data After Month 12 to Month 60
Lost to follow-up
17 Participants
15 Participants
13 Participants
Efficacy Event Data After Month 12 to Month 60
Discontinuation due to adverse event
10 Participants
8 Participants
4 Participants
Efficacy Event Data After Month 12 to Month 60
Therapy failure (composite endpoint)
38 Participants
35 Participants
36 Participants

Adverse Events

Standard Regimen

Serious events: 87 serious events
Other events: 121 other events
Deaths: 0 deaths

CNI-free

Serious events: 91 serious events
Other events: 134 other events
Deaths: 0 deaths

CNI-low

Serious events: 85 serious events
Other events: 133 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Standard Regimen
n=165 participants at risk
Myfortic, Sandimmun Optoral and corticosteroids
CNI-free
n=171 participants at risk
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids
CNI-low
n=161 participants at risk
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Blood and lymphatic system disorders
AGRANULOCYTOSIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Blood and lymphatic system disorders
ANAEMIA
0.61%
1/165
0.58%
1/171
0.62%
1/161
Blood and lymphatic system disorders
BONE MARROW OEDEMA
0.00%
0/165
0.58%
1/171
0.62%
1/161
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
0.00%
0/165
1.2%
2/171
0.00%
0/161
Blood and lymphatic system disorders
LEUKOPENIA
0.00%
0/165
2.3%
4/171
0.62%
1/161
Blood and lymphatic system disorders
NEPHROGENIC ANAEMIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Blood and lymphatic system disorders
PANCYTOPENIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Blood and lymphatic system disorders
POLYCYTHAEMIA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Blood and lymphatic system disorders
THROMBOCYTOPENIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Cardiac disorders
ACUTE CORONARY SYNDROME
0.00%
0/165
1.2%
2/171
0.00%
0/161
Cardiac disorders
ANGINA PECTORIS
1.2%
2/165
0.00%
0/171
0.00%
0/161
Cardiac disorders
AORTIC VALVE STENOSIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Cardiac disorders
ATRIAL FIBRILLATION
0.61%
1/165
1.2%
2/171
0.62%
1/161
Cardiac disorders
ATRIAL FLUTTER
0.61%
1/165
0.00%
0/171
0.00%
0/161
Cardiac disorders
BRADYCARDIA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Cardiac disorders
CARDIAC FAILURE
0.61%
1/165
0.58%
1/171
0.62%
1/161
Cardiac disorders
CARDIAC FAILURE ACUTE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Cardiac disorders
CORONARY ARTERY DISEASE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Ear and labyrinth disorders
VERTIGO
0.61%
1/165
0.00%
0/171
0.00%
0/161
Eye disorders
CATARACT
0.00%
0/165
0.58%
1/171
0.00%
0/161
Eye disorders
OPTIC ISCHAEMIC NEUROPATHY
0.00%
0/165
0.58%
1/171
0.00%
0/161
Gastrointestinal disorders
ASCITES
0.61%
1/165
0.00%
0/171
0.00%
0/161
Gastrointestinal disorders
COLITIS
0.00%
0/165
1.2%
2/171
0.00%
0/161
Gastrointestinal disorders
DIARRHOEA
0.61%
1/165
2.9%
5/171
2.5%
4/161
Gastrointestinal disorders
GASTRITIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
0.00%
0/165
0.58%
1/171
0.00%
0/161
Gastrointestinal disorders
HAEMATOCHEZIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Gastrointestinal disorders
HAEMORRHOIDAL HAEMORRHAGE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Gastrointestinal disorders
HAEMORRHOIDS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Gastrointestinal disorders
NAUSEA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Gastrointestinal disorders
NONINFECTIOUS PERITONITIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Gastrointestinal disorders
RECTAL PERFORATION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
0.00%
0/165
0.58%
1/171
0.00%
0/161
Gastrointestinal disorders
VOMITING
0.61%
1/165
0.58%
1/171
0.00%
0/161
General disorders
ATROPHY
0.00%
0/165
0.00%
0/171
0.62%
1/161
General disorders
CHILLS
0.61%
1/165
0.00%
0/171
0.00%
0/161
General disorders
DEVICE DISLOCATION
0.61%
1/165
0.00%
0/171
0.00%
0/161
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
0.61%
1/165
0.00%
0/171
0.00%
0/161
General disorders
GENERALISED OEDEMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
General disorders
IMPAIRED HEALING
0.61%
1/165
0.00%
0/171
0.62%
1/161
General disorders
LOCALISED OEDEMA
0.00%
0/165
0.58%
1/171
0.00%
0/161
General disorders
MULTI-ORGAN FAILURE
0.61%
1/165
0.00%
0/171
0.62%
1/161
General disorders
OEDEMA PERIPHERAL
0.61%
1/165
0.00%
0/171
0.00%
0/161
General disorders
PYREXIA
0.61%
1/165
1.8%
3/171
2.5%
4/161
General disorders
SUDDEN CARDIAC DEATH
0.61%
1/165
0.00%
0/171
0.00%
0/161
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Hepatobiliary disorders
CHOLELITHIASIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Immune system disorders
DRUG HYPERSENSITIVITY
0.00%
0/165
0.58%
1/171
0.00%
0/161
Immune system disorders
KIDNEY TRANSPLANT REJECTION
3.0%
5/165
3.5%
6/171
2.5%
4/161
Immune system disorders
TRANSPLANT REJECTION
3.6%
6/165
7.6%
13/171
5.6%
9/161
Infections and infestations
ANORECTAL INFECTION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
APPENDICITIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
ATYPICAL PNEUMONIA
1.2%
2/165
0.58%
1/171
0.00%
0/161
Infections and infestations
BK VIRUS INFECTION
0.00%
0/165
0.00%
0/171
0.62%
1/161
Infections and infestations
BRONCHITIS
1.2%
2/165
0.00%
0/171
0.62%
1/161
Infections and infestations
BRONCHOPNEUMONIA
0.61%
1/165
0.00%
0/171
1.2%
2/161
Infections and infestations
CANDIDA INFECTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
CYSTITIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
CYTOMEGALOVIRUS GASTROENTERITIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
CYTOMEGALOVIRUS INFECTION
3.6%
6/165
0.58%
1/171
2.5%
4/161
Infections and infestations
CYTOMEGALOVIRUS VIRAEMIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
DIABETIC GANGRENE
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
DIARRHOEA INFECTIOUS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Infections and infestations
ENCEPHALITIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
EPSTEIN-BARR VIRUS INFECTION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
ESCHERICHIA INFECTION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
FEBRILE INFECTION
0.61%
1/165
0.00%
0/171
1.2%
2/161
Infections and infestations
GANGRENE
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
GASTROENTERITIS
1.8%
3/165
3.5%
6/171
1.2%
2/161
Infections and infestations
GASTROENTERITIS NOROVIRUS
0.61%
1/165
0.58%
1/171
0.62%
1/161
Infections and infestations
GASTROINTESTINAL INFECTION
0.00%
0/165
0.58%
1/171
1.2%
2/161
Infections and infestations
GROIN ABSCESS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
HAEMATOMA INFECTION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
HERPES ZOSTER
1.2%
2/165
0.58%
1/171
0.62%
1/161
Infections and infestations
INFECTION
2.4%
4/165
0.58%
1/171
0.62%
1/161
Infections and infestations
INFLUENZA
0.00%
0/165
0.00%
0/171
0.62%
1/161
Infections and infestations
KIDNEY INFECTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
NECROTISING FASCIITIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
PNEUMOCYSTIS JIROVECII PNEUMONIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
PNEUMONIA
1.8%
3/165
3.5%
6/171
2.5%
4/161
Infections and infestations
PNEUMONIA CYTOMEGALOVIRAL
0.00%
0/165
1.2%
2/171
0.00%
0/161
Infections and infestations
PNEUMONIA INFLUENZAL
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
PNEUMONIA STREPTOCOCCAL
0.00%
0/165
0.00%
0/171
0.62%
1/161
Infections and infestations
PSEUDOMEMBRANOUS COLITIS
0.00%
0/165
0.00%
0/171
1.2%
2/161
Infections and infestations
PYELONEPHRITIS
0.61%
1/165
0.58%
1/171
0.00%
0/161
Infections and infestations
PYONEPHROSIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Infections and infestations
RENAL CYST INFECTION
0.61%
1/165
0.58%
1/171
0.00%
0/161
Infections and infestations
RESPIRATORY TRACT INFECTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
SALPINGO-OOPHORITIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
SEPSIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Infections and infestations
SEPTIC SHOCK
0.00%
0/165
0.00%
0/171
0.62%
1/161
Infections and infestations
SHUNT INFECTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
SINUSITIS
0.00%
0/165
0.58%
1/171
0.62%
1/161
Infections and infestations
STAPHYLOCOCCAL INFECTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Infections and infestations
URINARY TRACT INFECTION
9.1%
15/165
7.0%
12/171
4.3%
7/161
Infections and infestations
UROSEPSIS
3.6%
6/165
1.2%
2/171
4.3%
7/161
Infections and infestations
VARICELLA
0.61%
1/165
0.58%
1/171
0.00%
0/161
Infections and infestations
VIRAL INFECTION
0.00%
0/165
0.58%
1/171
0.62%
1/161
Infections and infestations
WOUND INFECTION
0.61%
1/165
0.58%
1/171
0.00%
0/161
Injury, poisoning and procedural complications
ACCIDENT
0.61%
1/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
ANKLE FRACTURE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
COMPLICATIONS OF TRANSPLANT SURGERY
0.61%
1/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
COMPLICATIONS OF TRANSPLANTED KIDNEY
3.0%
5/165
0.00%
0/171
1.2%
2/161
Injury, poisoning and procedural complications
CONTUSION
0.00%
0/165
0.58%
1/171
0.00%
0/161
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
FIBULA FRACTURE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
GRAFT LOSS
0.00%
0/165
1.2%
2/171
0.00%
0/161
Injury, poisoning and procedural complications
HEAT STROKE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
INCISIONAL HERNIA
0.61%
1/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
KIDNEY RUPTURE
0.00%
0/165
0.58%
1/171
0.00%
0/161
Injury, poisoning and procedural complications
OVERDOSE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
POST PROCEDURAL HAEMORRHAGE
1.2%
2/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
RENAL LYMPHOCELE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
SEROMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
SHUNT OCCLUSION
0.00%
0/165
0.58%
1/171
0.62%
1/161
Injury, poisoning and procedural complications
TIBIA FRACTURE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
TOXICITY TO VARIOUS AGENTS
1.2%
2/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
TRANSPLANT DYSFUNCTION
0.00%
0/165
0.00%
0/171
0.62%
1/161
Injury, poisoning and procedural complications
TRANSPLANT FAILURE
1.8%
3/165
2.9%
5/171
1.9%
3/161
Injury, poisoning and procedural complications
TRAUMATIC HAEMATOMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Injury, poisoning and procedural complications
VENA CAVA INJURY
0.00%
0/165
0.58%
1/171
0.00%
0/161
Investigations
BLOOD CREATININE INCREASED
8.5%
14/165
8.2%
14/171
10.6%
17/161
Investigations
CARBOHYDRATE ANTIGEN 125 INCREASED
0.00%
0/165
0.00%
0/171
0.62%
1/161
Investigations
CREATININE URINE INCREASED
0.00%
0/165
0.58%
1/171
0.00%
0/161
Investigations
CYTOMEGALOVIRUS TEST
1.2%
2/165
0.00%
0/171
0.00%
0/161
Investigations
CYTOMEGALOVIRUS TEST POSITIVE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Investigations
HAEMOGLOBIN DECREASED
0.00%
0/165
0.58%
1/171
0.00%
0/161
Investigations
HEPATIC ENZYME INCREASED
0.00%
0/165
0.00%
0/171
0.62%
1/161
Investigations
IMMUNOSUPPRESSANT DRUG LEVEL INCREASED
0.00%
0/165
0.00%
0/171
0.62%
1/161
Investigations
RED BLOOD CELL ACANTHOCYTES PRESENT
0.61%
1/165
0.00%
0/171
0.00%
0/161
Investigations
WEIGHT INCREASED
0.00%
0/165
0.00%
0/171
0.62%
1/161
Metabolism and nutrition disorders
DEHYDRATION
0.00%
0/165
0.58%
1/171
1.2%
2/161
Metabolism and nutrition disorders
DIABETES MELLITUS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Metabolism and nutrition disorders
HYPOCALCAEMIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Metabolism and nutrition disorders
HYPOGLYCAEMIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Metabolism and nutrition disorders
TUMOUR LYSIS SYNDROME
0.61%
1/165
0.00%
0/171
0.00%
0/161
Metabolism and nutrition disorders
TYPE 2 DIABETES MELLITUS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Musculoskeletal and connective tissue disorders
ARTHROPATHY
0.61%
1/165
0.00%
0/171
0.00%
0/161
Musculoskeletal and connective tissue disorders
JOINT SWELLING
0.00%
0/165
0.00%
0/171
0.62%
1/161
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Musculoskeletal and connective tissue disorders
MYALGIA
0.00%
0/165
0.00%
0/171
0.62%
1/161
Musculoskeletal and connective tissue disorders
MYOSITIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Musculoskeletal and connective tissue disorders
NEUROPATHIC ARTHROPATHY
0.00%
0/165
0.00%
0/171
0.62%
1/161
Musculoskeletal and connective tissue disorders
OSTEONECROSIS
1.2%
2/165
0.00%
0/171
1.2%
2/161
Musculoskeletal and connective tissue disorders
POST TRANSPLANT DISTAL LIMB SYNDROME
0.61%
1/165
0.00%
0/171
0.00%
0/161
Musculoskeletal and connective tissue disorders
RHABDOMYOLYSIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-CELL LYMPHOMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
0.61%
1/165
0.00%
0/171
0.62%
1/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BRONCHIAL CARCINOMA
0.61%
1/165
0.58%
1/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CLEAR CELL RENAL CELL CARCINOMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LIPOMA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO LIVER
0.61%
1/165
0.00%
0/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN CANCER
0.00%
0/165
0.58%
1/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
POST TRANSPLANT LYMPHOPROLIFERATIVE DISORDER
0.00%
0/165
0.58%
1/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL CELL CARCINOMA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SKIN PAPILLOMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Nervous system disorders
APHASIA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Nervous system disorders
CEREBRAL INFARCTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Nervous system disorders
CEREBROVASCULAR ACCIDENT
0.61%
1/165
1.2%
2/171
0.00%
0/161
Nervous system disorders
HEADACHE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Nervous system disorders
HEMIPARESIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Nervous system disorders
POLYNEUROPATHY
0.61%
1/165
0.00%
0/171
0.62%
1/161
Nervous system disorders
PRESYNCOPE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Psychiatric disorders
ADJUSTMENT DISORDER
0.00%
0/165
0.58%
1/171
0.00%
0/161
Psychiatric disorders
DEPRESSION
0.61%
1/165
0.00%
0/171
0.62%
1/161
Psychiatric disorders
PANIC ATTACK
0.00%
0/165
0.58%
1/171
0.00%
0/161
Psychiatric disorders
RESTLESSNESS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
ACUTE KIDNEY INJURY
0.00%
0/165
0.58%
1/171
1.2%
2/161
Renal and urinary disorders
GLOMERULOSCLEROSIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
HAEMATURIA
1.2%
2/165
0.00%
0/171
0.62%
1/161
Renal and urinary disorders
HYDRONEPHROSIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Renal and urinary disorders
KIDNEY FIBROSIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Renal and urinary disorders
NEPHRECTASIA
0.61%
1/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
NEPHROLITHIASIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Renal and urinary disorders
NEPHROPATHY
0.00%
0/165
0.00%
0/171
0.62%
1/161
Renal and urinary disorders
PROTEINURIA
0.00%
0/165
1.8%
3/171
0.62%
1/161
Renal and urinary disorders
REFLUX NEPHROPATHY
0.61%
1/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
RENAL ARTERY STENOSIS
1.2%
2/165
1.2%
2/171
0.00%
0/161
Renal and urinary disorders
RENAL CYST RUPTURED
0.00%
0/165
0.58%
1/171
0.00%
0/161
Renal and urinary disorders
RENAL FAILURE
0.00%
0/165
0.00%
0/171
0.62%
1/161
Renal and urinary disorders
RENAL IMPAIRMENT
1.2%
2/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
RENAL INFARCT
0.61%
1/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
RENAL TUBULAR ATROPHY
0.00%
0/165
0.58%
1/171
0.00%
0/161
Renal and urinary disorders
TUBULOINTERSTITIAL NEPHRITIS
0.00%
0/165
0.00%
0/171
1.2%
2/161
Renal and urinary disorders
URETERIC STENOSIS
1.2%
2/165
0.58%
1/171
0.00%
0/161
Renal and urinary disorders
URETHRAL OBSTRUCTION
0.61%
1/165
0.00%
0/171
0.00%
0/161
Renal and urinary disorders
URETHRAL STENOSIS
1.2%
2/165
0.58%
1/171
0.00%
0/161
Renal and urinary disorders
URINARY RETENTION
0.61%
1/165
0.00%
0/171
0.62%
1/161
Renal and urinary disorders
URINARY TRACT OBSTRUCTION
0.00%
0/165
0.58%
1/171
0.62%
1/161
Renal and urinary disorders
VESICOURETERIC REFLUX
0.00%
0/165
0.58%
1/171
0.00%
0/161
Reproductive system and breast disorders
OVARIAN CYST
0.00%
0/165
1.2%
2/171
0.00%
0/161
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Respiratory, thoracic and mediastinal disorders
ALVEOLITIS ALLERGIC
0.00%
0/165
0.58%
1/171
0.00%
0/161
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
1.2%
2/165
1.8%
3/171
0.00%
0/161
Respiratory, thoracic and mediastinal disorders
PLEURAL FIBROSIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Respiratory, thoracic and mediastinal disorders
PLEURISY
0.00%
0/165
0.58%
1/171
0.62%
1/161
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
0.00%
0/165
0.58%
1/171
0.00%
0/161
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
0.00%
0/165
1.2%
2/171
1.2%
2/161
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Respiratory, thoracic and mediastinal disorders
SLEEP APNOEA SYNDROME
0.00%
0/165
0.58%
1/171
0.00%
0/161
Skin and subcutaneous tissue disorders
SKIN ULCER
0.00%
0/165
0.00%
0/171
0.62%
1/161
Surgical and medical procedures
RESUSCITATION
0.00%
0/165
0.00%
0/171
0.62%
1/161
Vascular disorders
ARTERIAL HAEMORRHAGE
0.61%
1/165
0.00%
0/171
0.00%
0/161
Vascular disorders
ARTERIAL THROMBOSIS
0.61%
1/165
0.00%
0/171
0.62%
1/161
Vascular disorders
ARTERIOSCLEROSIS
0.00%
0/165
1.2%
2/171
0.62%
1/161
Vascular disorders
ARTERIOVENOUS FISTULA
0.00%
0/165
0.58%
1/171
0.00%
0/161
Vascular disorders
DEEP VEIN THROMBOSIS
0.61%
1/165
0.00%
0/171
0.62%
1/161
Vascular disorders
EMBOLISM
0.61%
1/165
0.00%
0/171
0.00%
0/161
Vascular disorders
EMBOLISM ARTERIAL
0.00%
0/165
0.58%
1/171
0.00%
0/161
Vascular disorders
HYPERTENSION
0.00%
0/165
0.58%
1/171
0.62%
1/161
Vascular disorders
HYPERTENSIVE CRISIS
0.61%
1/165
0.00%
0/171
0.00%
0/161
Vascular disorders
LYMPHOCELE
1.2%
2/165
0.58%
1/171
2.5%
4/161
Vascular disorders
LYMPHOEDEMA
0.00%
0/165
0.00%
0/171
0.62%
1/161
Vascular disorders
PERIPHERAL ARTERY STENOSIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Vascular disorders
THROMBOPHLEBITIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Vascular disorders
THROMBOSIS
0.00%
0/165
0.00%
0/171
1.9%
3/161
Vascular disorders
VASCULITIS
0.00%
0/165
0.58%
1/171
0.00%
0/161
Vascular disorders
VENOUS ANEURYSM
0.61%
1/165
0.00%
0/171
0.00%
0/161
Vascular disorders
VENOUS OCCLUSION
0.00%
0/165
0.00%
0/171
0.62%
1/161
Vascular disorders
VENOUS THROMBOSIS
0.00%
0/165
0.00%
0/171
0.62%
1/161
Vascular disorders
VENOUS THROMBOSIS LIMB
0.00%
0/165
0.58%
1/171
0.00%
0/161

Other adverse events

Other adverse events
Measure
Standard Regimen
n=165 participants at risk
Myfortic, Sandimmun Optoral and corticosteroids
CNI-free
n=171 participants at risk
CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids
CNI-low
n=161 participants at risk
CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids
Vascular disorders
HYPERTENSION
6.1%
10/165
2.9%
5/171
6.2%
10/161
Blood and lymphatic system disorders
ANAEMIA
3.0%
5/165
8.2%
14/171
1.2%
2/161
Blood and lymphatic system disorders
LEUKOPENIA
13.3%
22/165
15.2%
26/171
11.2%
18/161
Gastrointestinal disorders
APHTHOUS STOMATITIS
0.61%
1/165
19.3%
33/171
8.7%
14/161
Gastrointestinal disorders
DIARRHOEA
10.3%
17/165
19.9%
34/171
9.3%
15/161
Gastrointestinal disorders
NAUSEA
3.0%
5/165
4.7%
8/171
5.6%
9/161
General disorders
OEDEMA
9.1%
15/165
8.2%
14/171
13.7%
22/161
General disorders
OEDEMA PERIPHERAL
5.5%
9/165
9.9%
17/171
17.4%
28/161
Infections and infestations
CYTOMEGALOVIRUS INFECTION
7.3%
12/165
4.7%
8/171
2.5%
4/161
Infections and infestations
NASOPHARYNGITIS
17.6%
29/165
21.1%
36/171
23.0%
37/161
Infections and infestations
URINARY TRACT INFECTION
22.4%
37/165
18.1%
31/171
19.9%
32/161
Investigations
BLOOD CREATININE INCREASED
8.5%
14/165
6.4%
11/171
7.5%
12/161
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA
2.4%
4/165
4.7%
8/171
11.2%
18/161
Metabolism and nutrition disorders
HYPERLIPIDAEMIA
2.4%
4/165
3.5%
6/171
6.8%
11/161
Metabolism and nutrition disorders
HYPERURICAEMIA
5.5%
9/165
1.8%
3/171
2.5%
4/161
Metabolism and nutrition disorders
HYPOKALAEMIA
6.1%
10/165
11.7%
20/171
3.7%
6/161
Metabolism and nutrition disorders
IRON DEFICIENCY
6.1%
10/165
4.1%
7/171
4.3%
7/161
Musculoskeletal and connective tissue disorders
ARTHRALGIA
1.2%
2/165
6.4%
11/171
4.3%
7/161
Nervous system disorders
HEADACHE
4.2%
7/165
6.4%
11/171
6.2%
10/161
Renal and urinary disorders
PROTEINURIA
1.8%
3/165
3.5%
6/171
8.1%
13/161
Respiratory, thoracic and mediastinal disorders
COUGH
6.7%
11/165
4.7%
8/171
4.3%
7/161

Additional Information

Study Director

Novartis

Phone: 862-778-8300

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