Download PDF

Clinical Trial Results:
Multi-center, open-label, prospective, randomized, parallel group, long-term study investigating a standard regimen in de novo kidney transplant patients versus a CNI free regimen and a CNI low dose regimen.

Summary
EudraCT number	2006-007021-32
Trial protocol	DE
Global end of trial date	04 Jun 2015

Results information
Results version number	v1(current)
This version publication date	23 Jul 2016
First version publication date	23 Jul 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CRAD001ADE13

ISRCTN number

US NCT number

NCT00514514

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

04 Jun 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

04 Jun 2015

Global end of trial reached?

Yes

Global end of trial date

04 Jun 2015

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this trial was to demonstrate superiority of a CNI free regimen with respect to renal function at Month 12 post-transplant assessed by GFR (Nankivell method) as compared to the standard regimen in de novo kidney transplant patients.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. Rescue medication was permitted in the following circumstances: Biopsy-confirmed acute rejection episodes were to be treated with i.v. methylprednisolone at a recommended dose of 500-1000 mg for three days. Infection prophylaxis treatment was permitted for patients at high risk of CMV (a CMV positive donor organ transplanted into a CMV negative recipient). Hyperlipidemia medications to lower lipids (e.g., fluvastatin, Lescol®) were to be administered for patients with increased LDL-cholesterol and triglyceride levels.

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Jul 2007

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 780

Country: Number of subjects enrolled

Switzerland: 22

Worldwide total number of subjects

802

EEA total number of subjects

780

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

714

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

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.

Screening details

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).

Period 1 title

Pre-phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Standard regimen - Pre-phase

Arm description

Myfortic, Sandimmun Optoral, corticosteroids and Simulect® (if patient received transplant)

Arm type

Standard care

Investigational medicinal product name

Mycophenolate Sodium

Investigational medicinal product code

Other name

Myfortic

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Tablets containing 180 mg or 360 mg. 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day). Trade ware was used.

Investigational medicinal product name

Cyclosporine A

Investigational medicinal product code

Other name

Sandimmun Optoral

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Capsules containg 10,25,50 or 100 mg. Dosing was based on C0-h and/or C2-h level.

Investigational medicinal product name

Corticosteroids

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

During the first year after transplant, corticosteroids were added to the immunosuppressive regimen in all patients, according to local standard. A minimum dose of 5 mg prednisolone or equivalent was continued throughout this first year. After the first year, it was the investigators’ discretion to prescribe steroids or not.

Investigational medicinal product name

Basiliximab

Investigational medicinal product code

Other name

Simulect®

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

Vials containing 20 mg lyophilisate were supplied. 2 x 20 mg to be applied as 10 sec. bolus injection, i.v. on Day 0 (2 h before transplant) and on Day 4. Trade ware was used.

Number of subjects in period 1	Standard regimen - Pre-phase
Started	802
Completed	499
Not completed	303
Adverse event, serious fatal	10
condition no longer requires study drug	7
Consent withdrawn by subject	66
Adverse event, non-fatal	137
Administrative problems	2
abnormal lab values	23
abnormal test procedure results	15
Lost to follow-up	2
Lack of efficacy	35
Protocol deviation	6

Period 2 title

Randomized - 9 Month

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Standard regimen

Arm description

Myfortic, Sandimmun Optoral and corticosteroids

Arm type

Active comparator

Investigational medicinal product name

Mycophenolate Sodium

Investigational medicinal product code

Other name

Myfortic

Pharmaceutical forms

Capsule, Coated tablet

Routes of administration

Oral use

Dosage and administration details

Tablets containing 180 mg or 360 mg. 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day). Trade ware was used.

Investigational medicinal product name

Corticosteroids

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Cyclosporine A

Investigational medicinal product code

Other name

Sandimmun Optoral

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Capsules containing 10,25,50 or 100 mg. Dosing was based on C0-h and/or C2-h level.

CNI free regimen

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

RAD001

Other name

Certican

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Initially 1.5 mg/day, then based on blood levels (5-10 ng/mL in CNI free)

CNI low regimen

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

RAD001

Other name

Certican

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Initially 1.5 mg/day, then based on blood level (3-8 ng/mL in CNI low regimen)

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: This study had two baselines. The first baseline was day of transplant. Subjects received a standard regimen and Simulect® and were followed for 3 months. At month 3, subjects' eligibility was re-evaluated for randomization. Baseline 2 (Month 3) was used for the analysis.

Number of subjects in period 2 ^[2]	Standard regimen	CNI free regimen	CNI low regimen
Started	166	171	162
Randomized-received treatment	165	171	161
Started - Extension	145	139	134
Completed - Extension	108 ^[3]	117	113 ^[4]
Started - Non-randomized - Extension	95 ^[5]	0 ^[6]	0 ^[7]
Completed - Non-randomized-Extension	1 ^[8]	0 ^[9]	0 ^[10]
Completed	127	110	124
Not completed	39	61	38
Adverse event, serious fatal	3	2	2
Consent withdrawn by subject	7	7	5
Adverse event, non-fatal	25	44	27
Administrative problems	1	1	2
Abnormal laboratory values	-	3	1
Lack of efficacy	2	3	1
Protocol deviation	1	1	-

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: The number of subjects who entered the follow-up phase was greater than the number that completed the previous phase. The milestones were created to capture the number of subjects who entered the follow-up phase which included subjects who discontinued early from the randomization phase and non-randomized subjects. Non-Randomized subjects had received the Standard regimen drug treatment.

Baseline characteristics

Top of page

Reporting group title

Standard regimen

Reporting group description

Myfortic, Sandimmun Optoral and corticosteroids

Reporting group title

CNI free regimen

Reporting group description

Reporting group title

CNI low regimen

Reporting group description

Reporting group values	Standard regimen	CNI free regimen	CNI low regimen	Total
Number of subjects	166	171	162	499
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	147	158	150	455
From 65-84 years	19	13	12	44
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	49.9 ± 11.8	48.9 ± 12.5	48.6 ± 12.3	-
Gender, Male/Female
Units: Participants
Female	65	69	61	195
Male	101	102	101	304

End points

Top of page

Reporting group title

Standard regimen - Pre-phase

Reporting group description

Myfortic, Sandimmun Optoral, corticosteroids and Simulect® (if patient received transplant)

Reporting group title

Standard regimen

Reporting group description

Myfortic, Sandimmun Optoral and corticosteroids

Reporting group title

CNI free regimen

Reporting group description

Reporting group title

CNI low regimen

Reporting group description

Subject analysis set title

Standard Regimen - Month 3 BL2 to Month 60

Subject analysis set type

Intention-to-treat

Subject analysis set description

Analysis set includes initial ITT population from Month 3 (BL2). LOCF method applied.

Subject analysis set title

CNI free - Month 3 BL2 to Month 60

Subject analysis set type

Intention-to-treat

Subject analysis set description

Analysis set includes initial ITT population from Month 3 (BL2). LOCF method applied.

Subject analysis set title

CNI low - Month 3 BL2 to Month 60

Subject analysis set type

Intention-to-treat

Subject analysis set description

Analysis set includes initial ITT population from Month 3 (BL2). LOCF method applied.

Primary: Demonstrate superiority of a CNI free regimen in renal function assessed by GFR at Month 12 compared to the standard regimen

Top of page

End point title

Demonstrate superiority of a CNI free regimen in renal function assessed by GFR at Month 12 compared to the standard regimen ^[1]

End point description

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. P-values are not adjusted

End point type

Primary

End point timeframe

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

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The primary objective of this trial is to demonstrate superiority of a CNI free regimen with respect to renal function at Month 12 post-transplant assessed by GFR (Nankivell method) as compared to the standard regimen in de novo kidney transplant patients.

End point values	Standard regimen	CNI free regimen
Number of subjects analysed	159	163
Units: ml/min/1.73m²
least squares mean (confidence interval 95%)	63.03 (60.57 to 65.49)	68.59 (66.1 to 71.08)

BL2 (Month 3) to Month 12 in GFR-Nankivell Method

Comparison groups

Standard regimen v CNI free regimen

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

5.56

Confidence interval

level

95%

sides

2-sided

lower limit

2.82

upper limit

8.31

Secondary: GFR in ml/min per 1.73m² (LOCF) change from Baseline 2, calculated via Nankivell formula at Month 12 (ITT population)

Top of page

End point title

GFR in ml/min per 1.73m² (LOCF) change from Baseline 2, calculated via Nankivell formula at Month 12 (ITT population)

End point description

End point type

Secondary

End point timeframe

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

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	159	163	160
Units: ml/min/1.73m²
least squares mean (confidence interval 95%)	63.03 (60.57 to 65.49)	68.59 (66.1 to 71.08)	63.08 (60.62 to 65.55)

No statistical analyses for this end point

Secondary: GFR at Month 12 utilizing Modification of Diet in Renal Disease (MDRD) method

Top of page

End point title

GFR at Month 12 utilizing Modification of Diet in Renal Disease (MDRD) method

End point description

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.

End point type

Secondary

End point timeframe

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

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	151	158	157
Units: ml/min/1.73m²
least squares mean (confidence interval 95%)	50.23 (47.66 to 52.8)	56.36 (53.77 to 58.94)	50.24 (47.7 to 52.77)

No statistical analyses for this end point

Secondary: GFR at Month 12 utilizing Cockcroft-Gault formula

Top of page

End point title

GFR at Month 12 utilizing Cockcroft-Gault formula

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	160	164	160
Units: ml/min/1.73m²
least squares mean (confidence interval 95%)	60.18 (57.33 to 63.03)	64.87 (61.99 to 67.75)	61.16 (58.31 to 64.02)

No statistical analyses for this end point

Secondary: Change at Month 12 in serum creatine

Top of page

End point title

Change at Month 12 in serum creatine

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	160	165	160
Units: mg/dl
least squares mean (confidence interval 95%)	1.66 (1.51 to 1.81)	1.58 (1.43 to 1.73)	1.76 (1.61 to 1.91)

No statistical analyses for this end point

Secondary: Efficacy event data from Baseline 2 (Month 3) to Month 6

Top of page

End point title

Efficacy event data from Baseline 2 (Month 3) to Month 6

End point description

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).

End point type

Secondary

End point timeframe

From Baseline 2 (Month 3) to Month 6

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	165	171	161
Units: Participants
BPAR	6	15	10
Graft loss	0	1	1
Death	1	1	0
Lost to follow-up	0	0	0
Discontinuation due to lack of efficacy	1	2	1
Discontinuation due to adverse event	8	26	13
Therapy failure composite	14	37	19

No statistical analyses for this end point

Secondary: Efficacy event data Baseline 2 (Month 3) to Month 12

Top of page

End point title

Efficacy event data Baseline 2 (Month 3) to Month 12

End point description

End point type

Secondary

End point timeframe

From Baseline 2 (Month 3) to Month 12

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	165	171	161
Units: Participants
BPAR	13	20	13
Graft loss	1	2	1
Death	3	2	2
Lost to follow-up	0	0	0
Discontinuation due to lack of efficacy	2	3	1
Discontinuation due to adverse event	25	44	27
Therapy failure composite	34	58	35

No statistical analyses for this end point

Secondary: Change from BL2 (Month 3) to Month 12 in Cardiovascular risk (Framingham score; 10-year Cardiovascular risk)

Top of page

End point title

Change from BL2 (Month 3) to Month 12 in Cardiovascular risk (Framingham score; 10-year Cardiovascular risk)

End point description

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.

End point type

Secondary

End point timeframe

From Baseline 2 (Month 3) to Month 12

End point values	Standard regimen	CNI free regimen	CNI low regimen
Number of subjects analysed	165	171	161
Units: Score of CHD Risk in 10 years
arithmetic mean (standard deviation)
Baseline 1/Visit 1	10.9 ± 8	10.2 ± 7.4	9.5 ± 6.9
Baseline 2/Month 3	10.3 ± 7.7	8.8 ± 5.9	9.3 ± 7.2
Month 12	9.4 ± 6.8	9.1 ± 6.4	8.7 ± 6.8
Change from Baseline 2 to Month 12	-0.7 ± 5.8	0.4 ± 5.1	-0.7 ± 5.4

No statistical analyses for this end point

Secondary: GFR calculated via Nankivell, Cockcroft, MDRD methods at Month 60 (ITT population)

Top of page

End point title

GFR calculated via Nankivell, Cockcroft, MDRD methods at Month 60 (ITT population)

End point description

End point type

Secondary

End point timeframe

From randomization at BL2 (Month 3) to Month 60

End point values	Standard Regimen - Month 3 BL2 to Month 60	CNI free - Month 3 BL2 to Month 60	CNI low - Month 3 BL2 to Month 60
Number of subjects analysed	162	165	159
Units: ml/min/1.73m²
least squares mean (confidence interval 95%)
Nankivell (160,163,159)	60.24 (57.11 to 63.38)	66.98 (63.78 to 70.17)	58.74 (55.58 to 61.9)
Cockcroft (162,165,159)	55.92 (52.36 to 59.48)	61.6 (57.99 to 65.2)	52.91 (49.32 to 56.5)
MDRD (152,159,156)	47.56 (44.58 to 50.54)	53.41 (50.4 to 56.42)	44.79 (41.83 to 47.74)

No statistical analyses for this end point

Secondary: Change at Month 60 in serum creatine

Top of page

End point title

Change at Month 60 in serum creatine

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Standard Regimen - Month 3 BL2 to Month 60	CNI free - Month 3 BL2 to Month 60	CNI low - Month 3 BL2 to Month 60
Number of subjects analysed	162	165	159
Units: mg/dl
least squares mean (confidence interval 95%)
Serum creatinine (162,166,159)	1.94 (1.72 to 2.15)	1.69 (1.47 to 1.91)	2.01 (1.79 to 2.23)

No statistical analyses for this end point

Secondary: Efficacy event data after Month 12 to Month 60

Top of page

End point title

Efficacy event data after Month 12 to Month 60

End point description

End point type

Secondary

End point timeframe

Events starting after Month 12

End point values	Standard Regimen - Month 3 BL2 to Month 60	CNI free - Month 3 BL2 to Month 60	CNI low - Month 3 BL2 to Month 60
Number of subjects analysed	162	165	159
Units: Participants
BPAR (165,171,161)	13	13	12
Graft loss(165,171,161)	7	7	3
Death(165,171,161)	7	4	9
Lost to follow-up(165,171,161)	17	15	13
Discontinuation due to adverse event(165,171,161)	10	8	4
Therapy failure (composite endpoint)(165,171,161)	38	35	36

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Standard

Reporting group description

Standard

Reporting group title

CNI-free

Reporting group description

CNI-free

Reporting group title

CNI-low

Reporting group description

CNI-low

Serious adverse events	Standard	CNI-free	CNI-low
Total subjects affected by serious adverse events
subjects affected / exposed	87 / 165 (52.73%)	91 / 171 (53.22%)	85 / 161 (52.80%)
number of deaths (all causes)	3	2	2
number of deaths resulting from adverse events	0	2	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-CELL LYMPHOMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BASAL CELL CARCINOMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRONCHIAL CARCINOMA
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	1 / 1	0 / 0
CLEAR CELL RENAL CELL CARCINOMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LIPOMA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
METASTASES TO LIVER
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OVARIAN CANCER
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POST TRANSPLANT LYMPHOPROLIFERATIVE DISORDER
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
RENAL CELL CARCINOMA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SKIN PAPILLOMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SQUAMOUS CELL CARCINOMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
ARTERIAL HAEMORRHAGE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARTERIAL THROMBOSIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARTERIOSCLEROSIS
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARTERIOVENOUS FISTULA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEEP VEIN THROMBOSIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EMBOLISM
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EMBOLISM ARTERIAL
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERTENSION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERTENSIVE CRISIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LYMPHOCELE
subjects affected / exposed	2 / 165 (1.21%)	1 / 171 (0.58%)	4 / 161 (2.48%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LYMPHOEDEMA
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PERIPHERAL ARTERY STENOSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THROMBOPHLEBITIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THROMBOSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	3 / 161 (1.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VASCULITIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VENOUS ANEURYSM
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VENOUS OCCLUSION
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VENOUS THROMBOSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VENOUS THROMBOSIS LIMB
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
RESUSCITATION
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
ATROPHY
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHILLS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEVICE DISLOCATION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GENERAL PHYSICAL HEALTH DETERIORATION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GENERALISED OEDEMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
IMPAIRED HEALING
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LOCALISED OEDEMA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MULTI-ORGAN FAILURE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OEDEMA PERIPHERAL
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	1 / 165 (0.61%)	3 / 171 (1.75%)	4 / 161 (2.48%)
occurrences causally related to treatment / all	0 / 1	1 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SUDDEN CARDIAC DEATH
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Immune system disorders
DRUG HYPERSENSITIVITY
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
KIDNEY TRANSPLANT REJECTION
subjects affected / exposed	5 / 165 (3.03%)	6 / 171 (3.51%)	4 / 161 (2.48%)
occurrences causally related to treatment / all	3 / 5	2 / 6	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TRANSPLANT REJECTION
subjects affected / exposed	6 / 165 (3.64%)	13 / 171 (7.60%)	9 / 161 (5.59%)
occurrences causally related to treatment / all	2 / 6	5 / 13	6 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
OVARIAN CYST
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VAGINAL HAEMORRHAGE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
ALVEOLITIS ALLERGIC
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DYSPNOEA
subjects affected / exposed	2 / 165 (1.21%)	3 / 171 (1.75%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PLEURAL FIBROSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PLEURISY
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PRODUCTIVE COUGH
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 0	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY OEDEMA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SLEEP APNOEA SYNDROME
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
ADJUSTMENT DISORDER
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEPRESSION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PANIC ATTACK
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RESTLESSNESS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
BLOOD CREATININE INCREASED
subjects affected / exposed	14 / 165 (8.48%)	14 / 171 (8.19%)	17 / 161 (10.56%)
occurrences causally related to treatment / all	6 / 16	4 / 16	7 / 21
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CARBOHYDRATE ANTIGEN 125 INCREASED
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CREATININE URINE INCREASED
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS TEST
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS TEST POSITIVE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMOGLOBIN DECREASED
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEPATIC ENZYME INCREASED
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
IMMUNOSUPPRESSANT DRUG LEVEL INCREASED
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RED BLOOD CELL ACANTHOCYTES PRESENT
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WEIGHT INCREASED
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
ACCIDENT
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
ANKLE FRACTURE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COMPLICATIONS OF TRANSPLANT SURGERY
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COMPLICATIONS OF TRANSPLANTED KIDNEY
subjects affected / exposed	5 / 165 (3.03%)	0 / 171 (0.00%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	2 / 5	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CONTUSION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEMORAL NECK FRACTURE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FIBULA FRACTURE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GRAFT LOSS
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEAT STROKE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INCISIONAL HERNIA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
KIDNEY RUPTURE
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OVERDOSE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POST PROCEDURAL HAEMORRHAGE
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL LYMPHOCELE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEROMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SHUNT OCCLUSION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TIBIA FRACTURE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TOXICITY TO VARIOUS AGENTS
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TRANSPLANT DYSFUNCTION
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TRANSPLANT FAILURE
subjects affected / exposed	3 / 165 (1.82%)	5 / 171 (2.92%)	3 / 161 (1.86%)
occurrences causally related to treatment / all	1 / 3	4 / 5	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TRAUMATIC HAEMATOMA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VENA CAVA INJURY
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
ACUTE CORONARY SYNDROME
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANGINA PECTORIS
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
AORTIC VALVE STENOSIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	1 / 165 (0.61%)	2 / 171 (1.17%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ATRIAL FLUTTER
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRADYCARDIA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CARDIAC FAILURE
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
CARDIAC FAILURE ACUTE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
CORONARY ARTERY DISEASE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
APHASIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CEREBRAL INFARCTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CEREBROVASCULAR ACCIDENT
subjects affected / exposed	1 / 165 (0.61%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEADACHE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEMIPARESIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POLYNEUROPATHY
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PRESYNCOPE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
AGRANULOCYTOSIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANAEMIA
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BONE MARROW OEDEMA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LEUKOPENIA
subjects affected / exposed	0 / 165 (0.00%)	4 / 171 (2.34%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	5 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEPHROGENIC ANAEMIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PANCYTOPENIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POLYCYTHAEMIA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THROMBOCYTOPENIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
VERTIGO
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
CATARACT
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OPTIC ISCHAEMIC NEUROPATHY
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
ASCITES
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLITIS
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	1 / 165 (0.61%)	5 / 171 (2.92%)	4 / 161 (2.48%)
occurrences causally related to treatment / all	1 / 1	1 / 5	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTRITIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMATOCHEZIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMORRHOIDAL HAEMORRHAGE
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMORRHOIDS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NONINFECTIOUS PERITONITIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RECTAL PERFORATION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHOLELITHIASIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
SKIN ULCER
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GLOMERULOSCLEROSIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMATURIA
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYDRONEPHROSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
KIDNEY FIBROSIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEPHRECTASIA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEPHROLITHIASIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEPHROPATHY
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PROTEINURIA
subjects affected / exposed	0 / 165 (0.00%)	3 / 171 (1.75%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
REFLUX NEPHROPATHY
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL ARTERY STENOSIS
subjects affected / exposed	2 / 165 (1.21%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL CYST RUPTURED
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL FAILURE
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL IMPAIRMENT
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL INFARCT
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL TUBULAR ATROPHY
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TUBULOINTERSTITIAL NEPHRITIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URETERIC STENOSIS
subjects affected / exposed	2 / 165 (1.21%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URETHRAL OBSTRUCTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URETHRAL STENOSIS
subjects affected / exposed	2 / 165 (1.21%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY RETENTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY TRACT OBSTRUCTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VESICOURETERIC REFLUX
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
ARTHROPATHY
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
JOINT SWELLING
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MUSCULAR WEAKNESS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYALGIA
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYOSITIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEUROPATHIC ARTHROPATHY
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OSTEONECROSIS
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POST TRANSPLANT DISTAL LIMB SYNDROME
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RHABDOMYOLYSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
ANORECTAL INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
APPENDICITIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ATYPICAL PNEUMONIA
subjects affected / exposed	2 / 165 (1.21%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BK VIRUS INFECTION
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRONCHITIS
subjects affected / exposed	2 / 165 (1.21%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRONCHOPNEUMONIA
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CANDIDA INFECTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYSTITIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS GASTROENTERITIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS INFECTION
subjects affected / exposed	6 / 165 (3.64%)	1 / 171 (0.58%)	4 / 161 (2.48%)
occurrences causally related to treatment / all	1 / 6	0 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYTOMEGALOVIRUS VIRAEMIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIABETIC GANGRENE
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIARRHOEA INFECTIOUS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENCEPHALITIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
EPSTEIN-BARR VIRUS INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ESCHERICHIA INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEBRILE INFECTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 1	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GANGRENE
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROENTERITIS
subjects affected / exposed	3 / 165 (1.82%)	6 / 171 (3.51%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 3	1 / 6	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROENTERITIS NOROVIRUS
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GROIN ABSCESS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMATOMA INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HERPES ZOSTER
subjects affected / exposed	2 / 165 (1.21%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 2	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFECTION
subjects affected / exposed	4 / 165 (2.42%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	3 / 4	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFLUENZA
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
KIDNEY INFECTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NECROTISING FASCIITIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
PNEUMOCYSTIS JIROVECII PNEUMONIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	3 / 165 (1.82%)	6 / 171 (3.51%)	4 / 161 (2.48%)
occurrences causally related to treatment / all	1 / 4	4 / 7	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA CYTOMEGALOVIRAL
subjects affected / exposed	0 / 165 (0.00%)	2 / 171 (1.17%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA INFLUENZAL
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA STREPTOCOCCAL
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PSEUDOMEMBRANOUS COLITIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PYELONEPHRITIS
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PYONEPHROSIS
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RENAL CYST INFECTION
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SALPINGO-OOPHORITIS
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
SEPTIC SHOCK
subjects affected / exposed	0 / 165 (0.00%)	0 / 171 (0.00%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SHUNT INFECTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SINUSITIS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
STAPHYLOCOCCAL INFECTION
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	15 / 165 (9.09%)	12 / 171 (7.02%)	7 / 161 (4.35%)
occurrences causally related to treatment / all	11 / 19	4 / 13	5 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
UROSEPSIS
subjects affected / exposed	6 / 165 (3.64%)	2 / 171 (1.17%)	7 / 161 (4.35%)
occurrences causally related to treatment / all	3 / 7	0 / 2	4 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VARICELLA
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VIRAL INFECTION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	1 / 161 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WOUND INFECTION
subjects affected / exposed	1 / 165 (0.61%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	2 / 161 (1.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIABETES MELLITUS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOCALCAEMIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOGLYCAEMIA
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TUMOUR LYSIS SYNDROME
subjects affected / exposed	1 / 165 (0.61%)	0 / 171 (0.00%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
TYPE 2 DIABETES MELLITUS
subjects affected / exposed	0 / 165 (0.00%)	1 / 171 (0.58%)	0 / 161 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Standard	CNI-free	CNI-low
Total subjects affected by non serious adverse events
subjects affected / exposed	121 / 165 (73.33%)	134 / 171 (78.36%)	133 / 161 (82.61%)
Investigations
BLOOD CREATININE INCREASED
subjects affected / exposed	14 / 165 (8.48%)	11 / 171 (6.43%)	12 / 161 (7.45%)
occurrences all number	17	12	13
Vascular disorders
HYPERTENSION
subjects affected / exposed	10 / 165 (6.06%)	5 / 171 (2.92%)	10 / 161 (6.21%)
occurrences all number	10	5	10
Nervous system disorders
HEADACHE
subjects affected / exposed	7 / 165 (4.24%)	11 / 171 (6.43%)	10 / 161 (6.21%)
occurrences all number	7	12	13
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	5 / 165 (3.03%)	14 / 171 (8.19%)	2 / 161 (1.24%)
occurrences all number	5	14	2
LEUKOPENIA
subjects affected / exposed	22 / 165 (13.33%)	26 / 171 (15.20%)	18 / 161 (11.18%)
occurrences all number	24	31	19
General disorders and administration site conditions
OEDEMA
subjects affected / exposed	15 / 165 (9.09%)	14 / 171 (8.19%)	22 / 161 (13.66%)
occurrences all number	15	14	22
OEDEMA PERIPHERAL
subjects affected / exposed	9 / 165 (5.45%)	17 / 171 (9.94%)	28 / 161 (17.39%)
occurrences all number	9	17	32
Gastrointestinal disorders
APHTHOUS STOMATITIS
subjects affected / exposed	1 / 165 (0.61%)	33 / 171 (19.30%)	14 / 161 (8.70%)
occurrences all number	1	38	18
DIARRHOEA
subjects affected / exposed	17 / 165 (10.30%)	34 / 171 (19.88%)	15 / 161 (9.32%)
occurrences all number	19	37	15
NAUSEA
subjects affected / exposed	5 / 165 (3.03%)	8 / 171 (4.68%)	9 / 161 (5.59%)
occurrences all number	5	9	9
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	11 / 165 (6.67%)	8 / 171 (4.68%)	7 / 161 (4.35%)
occurrences all number	13	9	7
Renal and urinary disorders
PROTEINURIA
subjects affected / exposed	3 / 165 (1.82%)	6 / 171 (3.51%)	13 / 161 (8.07%)
occurrences all number	3	7	14
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	2 / 165 (1.21%)	11 / 171 (6.43%)	7 / 161 (4.35%)
occurrences all number	2	12	8
Infections and infestations
CYTOMEGALOVIRUS INFECTION
subjects affected / exposed	12 / 165 (7.27%)	8 / 171 (4.68%)	4 / 161 (2.48%)
occurrences all number	14	8	4
NASOPHARYNGITIS
subjects affected / exposed	29 / 165 (17.58%)	36 / 171 (21.05%)	37 / 161 (22.98%)
occurrences all number	31	45	44
URINARY TRACT INFECTION
subjects affected / exposed	37 / 165 (22.42%)	31 / 171 (18.13%)	32 / 161 (19.88%)
occurrences all number	43	45	47
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA
subjects affected / exposed	4 / 165 (2.42%)	8 / 171 (4.68%)	18 / 161 (11.18%)
occurrences all number	4	8	18
HYPERLIPIDAEMIA
subjects affected / exposed	4 / 165 (2.42%)	6 / 171 (3.51%)	11 / 161 (6.83%)
occurrences all number	4	6	11
HYPERURICAEMIA
subjects affected / exposed	9 / 165 (5.45%)	3 / 171 (1.75%)	4 / 161 (2.48%)
occurrences all number	9	3	4
HYPOKALAEMIA
subjects affected / exposed	10 / 165 (6.06%)	20 / 171 (11.70%)	6 / 161 (3.73%)
occurrences all number	10	22	6
IRON DEFICIENCY
subjects affected / exposed	10 / 165 (6.06%)	7 / 171 (4.09%)	7 / 161 (4.35%)
occurrences all number	10	7	7

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

31 Jan 2008

Amendment was issued approximately 6 months after FPFV changed the lower target therapeutic limit for Certican whole blood trough levels in the CNI free regimen from 6 ng/ml to 5 ng/ml, addressed the assessment and follow-up of patients after Month 12/ End of Study (recording of information) and the SAE reporting of patients in the extension period.

26 Jan 2009

Amendment added a post-text supplement to describe optional biomarker assessments to be performed as a sub-study.

01 Feb 2010

Amendment addressed the documentation of AEs, concomitant medication and immunosuppressive medication for patients who were or were not randomized. Additionally, several inconsistencies within the protocol were corrected.

16 May 2011

Amendment addressed the SAE reporting of patients suffering from rejection.

27 Oct 2011

Amendment was issued when recruitment was 100% complete and addressed the follow-up of patients who were not randomized and who were to be followed up in the former version of the protocol for additional four years. These patients never received the foreseen treatment in the protocol and therefore no additional information would be generated.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Milestones were added to Subject Disposition for subjects entering and completing the extension period which included randomized subjects from treatment period and non-randomized subjects from Pre-phase Period.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Multi-center, open-label, prospective, randomized, parallel group, long-term study investigating a standard regimen in de novo kidney transplant patients versus a CNI free regimen and a CNI low dose regimen.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Demonstrate superiority of a CNI free regimen in renal function assessed by GFR at Month 12 compared to the standard regimen

Primary: Demonstrate superiority of a CNI free regimen in renal function assessed by GFR at Month 12 compared to the standard regimen

Secondary: GFR in ml/min per 1.73m² (LOCF) change from Baseline 2, calculated via Nankivell formula at Month 12 (ITT population)

Secondary: GFR in ml/min per 1.73m² (LOCF) change from Baseline 2, calculated via Nankivell formula at Month 12 (ITT population)

Secondary: GFR at Month 12 utilizing Modification of Diet in Renal Disease (MDRD) method

Secondary: GFR at Month 12 utilizing Modification of Diet in Renal Disease (MDRD) method

Secondary: GFR at Month 12 utilizing Cockcroft-Gault formula

Secondary: GFR at Month 12 utilizing Cockcroft-Gault formula

Secondary: Change at Month 12 in serum creatine

Secondary: Change at Month 12 in serum creatine

Secondary: Efficacy event data from Baseline 2 (Month 3) to Month 6

Secondary: Efficacy event data from Baseline 2 (Month 3) to Month 6

Secondary: Efficacy event data Baseline 2 (Month 3) to Month 12

Secondary: Efficacy event data Baseline 2 (Month 3) to Month 12

Secondary: Change from BL2 (Month 3) to Month 12 in Cardiovascular risk (Framingham score; 10-year Cardiovascular risk)

Secondary: Change from BL2 (Month 3) to Month 12 in Cardiovascular risk (Framingham score; 10-year Cardiovascular risk)

Secondary: GFR calculated via Nankivell, Cockcroft, MDRD methods at Month 60 (ITT population)

Secondary: GFR calculated via Nankivell, Cockcroft, MDRD methods at Month 60 (ITT population)

Secondary: Change at Month 60 in serum creatine

Secondary: Change at Month 60 in serum creatine

Secondary: Efficacy event data after Month 12 to Month 60

Secondary: Efficacy event data after Month 12 to Month 60

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Multi-center, open-label, prospective, randomized, parallel group, long-term study investigating a standard regimen in de novo kidney transplant patients versus a CNI free regimen and a CNI low dose regimen.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Demonstrate superiority of a CNI free regimen in renal function assessed by GFR at Month 12 compared to the standard regimen

Primary: Demonstrate superiority of a CNI free regimen in renal function assessed by GFR at Month 12 compared to the standard regimen

Secondary: GFR in ml/min per 1.73m² (LOCF) change from Baseline 2, calculated via Nankivell formula at Month 12 (ITT population)

Secondary: GFR in ml/min per 1.73m² (LOCF) change from Baseline 2, calculated via Nankivell formula at Month 12 (ITT population)

Secondary: GFR at Month 12 utilizing Modification of Diet in Renal Disease (MDRD) method

Secondary: GFR at Month 12 utilizing Modification of Diet in Renal Disease (MDRD) method

Secondary: GFR at Month 12 utilizing Cockcroft-Gault formula

Secondary: GFR at Month 12 utilizing Cockcroft-Gault formula

Secondary: Change at Month 12 in serum creatine

Secondary: Change at Month 12 in serum creatine

Secondary: Efficacy event data from Baseline 2 (Month 3) to Month 6

Secondary: Efficacy event data from Baseline 2 (Month 3) to Month 6

Secondary: Efficacy event data Baseline 2 (Month 3) to Month 12

Secondary: Efficacy event data Baseline 2 (Month 3) to Month 12

Secondary: Change from BL2 (Month 3) to Month 12 in Cardiovascular risk (Framingham score; 10-year Cardiovascular risk)

Secondary: Change from BL2 (Month 3) to Month 12 in Cardiovascular risk (Framingham score; 10-year Cardiovascular risk)

Secondary: GFR calculated via Nankivell, Cockcroft, MDRD methods at Month 60 (ITT population)

Secondary: GFR calculated via Nankivell, Cockcroft, MDRD methods at Month 60 (ITT population)

Secondary: Change at Month 60 in serum creatine

Secondary: Change at Month 60 in serum creatine

Secondary: Efficacy event data after Month 12 to Month 60

Secondary: Efficacy event data after Month 12 to Month 60

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Multi-center, open-label, prospective, randomized, parallel group, long-term study investigating a standard regimen in de novo kidney transplant patients versus a CNI free regimen and a CNI low dose regimen.