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    Clinical Trial Results:
    An Open Label Comparative Study of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids With Further CSA Elimination In The Rapamune Arm With The Introduction of MMF

    Summary
    EudraCT number
    2014-004102-15
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    26 Mar 2008

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Jun 2016
    First version publication date
    01 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    0468H-102012
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01601821
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Alias identifier: B1741220
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer ClinicalTrials.gov Call Center, 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer ClinicalTrials.gov Call Center, 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Oct 2010
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Mar 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the safety and efficacy of cyclosporine (CsA) + mycophenolate mofetil (MMF) + corticosteroids (Cs) to CsA + Rapamune + Cs with CsA elimination in the Rapamune arm with the introduction of MMF in de novo renal allograft recipients.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Apr 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    1 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Iran, Islamic Republic of: 245
    Worldwide total number of subjects
    245
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    9
    Adults (18-64 years)
    228
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 245 subjects were enrolled in the study from Iran and study started on 3- Apr-2006 and completed on 26-Mar-2008.

    Period 1
    Period 1 title
    Overall Study (Overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    CsA+Rapamune+CS
    Arm description
    Month 0-3: rapamune 6 milligram (mg) tablet orally once as a loading dose within 48 hours of transplantation, followed by rapamune 2 mg tablet orally once daily as a maintenance dose to achieve a target trough level of 8-15 nanogram per milliliter (ng/mL) in combination with CsA tablets orally to achieve a trough level of 150-250 ng/mL. Month 4-6: CsA was withdrawn abruptly, MMF tablet orally at a dose of 1-1.5 grams per day (g/day) and rapamune dose adjusted to achieve a target trough level of 10-15 ng/mL. Month 7-12: rapamune dose adjusted to achieve a target trough level of 8-12 ng/mL, MMF tablet orally at a dose of 1-1.5 g/day. Subjects also received CS tablets orally as per local practice with a minimum daily dose of 5 mg over 12 months.
    Arm type
    Active comparator

    Investigational medicinal product name
    CsA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    CsA tablets were administered orally to achieve a trough level of 150-250 ng/mL. In month 4-6 CsA was withdrawn abruptly.

    Investigational medicinal product name
    CS
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    CS tablets were administered orally as per local practice with a minimum daily dose of 5 mg over 12 months.

    Investigational medicinal product name
    Rapamune
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Rapamune 6 mg tablet was administered orally once as a loading dose within 48 hours of transplantation, followed by rapamune 2 mg tablet orally once daily as a maintenance dose.

    Arm title
    CsA+MMF+CS
    Arm description
    Month 0-5: CsA tablets orally to achieve a trough level of 150-300 ng/mL. Month 6-12: CsA tablets orally to achieve a trough level of 100-200 ng/mL. Subjects also received MMF tablet orally at a dose of 2 g/day and CS tablets orally as per local practice with a minimum daily dose of 5 mg over 12 months.
    Arm type
    Active comparator

    Investigational medicinal product name
    CsA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    CsA tablets were administered orally to achieve a trough level of 150-250 ng/mL. In month 4-6 CsA was withdrawn abruptly.

    Investigational medicinal product name
    CS
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    CS tablets were administered orally as per local practice with a minimum daily dose of 5 mg over 12 months.

    Investigational medicinal product name
    MMF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MMF tablet was administered orally at a dose of 2 g/day.

    Number of subjects in period 1
    CsA+Rapamune+CS CsA+MMF+CS
    Started
    125
    120
    Completed
    96
    91
    Not completed
    29
    29
         Protocol deviation
    2
    2
         Adverse event, serious fatal
    2
    5
         Study Events
    7
    1
         Graft Loss
    6
    6
         Unspecified
    5
    1
         Consent withdrawn by subject
    1
    -
         Lost to follow-up
    6
    14

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    CsA+Rapamune+CS
    Reporting group description
    Month 0-3: rapamune 6 milligram (mg) tablet orally once as a loading dose within 48 hours of transplantation, followed by rapamune 2 mg tablet orally once daily as a maintenance dose to achieve a target trough level of 8-15 nanogram per milliliter (ng/mL) in combination with CsA tablets orally to achieve a trough level of 150-250 ng/mL. Month 4-6: CsA was withdrawn abruptly, MMF tablet orally at a dose of 1-1.5 grams per day (g/day) and rapamune dose adjusted to achieve a target trough level of 10-15 ng/mL. Month 7-12: rapamune dose adjusted to achieve a target trough level of 8-12 ng/mL, MMF tablet orally at a dose of 1-1.5 g/day. Subjects also received CS tablets orally as per local practice with a minimum daily dose of 5 mg over 12 months.

    Reporting group title
    CsA+MMF+CS
    Reporting group description
    Month 0-5: CsA tablets orally to achieve a trough level of 150-300 ng/mL. Month 6-12: CsA tablets orally to achieve a trough level of 100-200 ng/mL. Subjects also received MMF tablet orally at a dose of 2 g/day and CS tablets orally as per local practice with a minimum daily dose of 5 mg over 12 months.

    Reporting group values
    CsA+Rapamune+CS CsA+MMF+CS Total
    Number of subjects
    125 120 245
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    38.2 ± 13.4 41.6 ± 15.1 -
    Gender, Male/Female
    Units: subjects
        Female
    47 45 92
        Male
    78 75 153

    End points

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    End points reporting groups
    Reporting group title
    CsA+Rapamune+CS
    Reporting group description
    Month 0-3: rapamune 6 milligram (mg) tablet orally once as a loading dose within 48 hours of transplantation, followed by rapamune 2 mg tablet orally once daily as a maintenance dose to achieve a target trough level of 8-15 nanogram per milliliter (ng/mL) in combination with CsA tablets orally to achieve a trough level of 150-250 ng/mL. Month 4-6: CsA was withdrawn abruptly, MMF tablet orally at a dose of 1-1.5 grams per day (g/day) and rapamune dose adjusted to achieve a target trough level of 10-15 ng/mL. Month 7-12: rapamune dose adjusted to achieve a target trough level of 8-12 ng/mL, MMF tablet orally at a dose of 1-1.5 g/day. Subjects also received CS tablets orally as per local practice with a minimum daily dose of 5 mg over 12 months.

    Reporting group title
    CsA+MMF+CS
    Reporting group description
    Month 0-5: CsA tablets orally to achieve a trough level of 150-300 ng/mL. Month 6-12: CsA tablets orally to achieve a trough level of 100-200 ng/mL. Subjects also received MMF tablet orally at a dose of 2 g/day and CS tablets orally as per local practice with a minimum daily dose of 5 mg over 12 months.

    Primary: Incidence of Efficacy Failure

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    End point title
    Incidence of Efficacy Failure
    End point description
    Efficacy failure was defined as first occurrence of either biopsy confirmed acute rejection, graft loss or death within 12 months of post-transplantation. Percentage of subjects with efficacy failure was reported.
    End point type
    Primary
    End point timeframe
    Baseline up to Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    105 [1]
    104 [2]
    Units: percentage of subjects
        number (not applicable)
    11.4
    13.5
    Notes
    [1] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [2] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Analysis for incidence of efficacy failure
    Statistical analysis description
    Chi-square test was used to test superiority of arm CsA+Rapamune+CS versus arm CsA+MMF+CS.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.341
    Method
    Chi-squared
    Parameter type
    Percent Difference
    Point estimate
    -2
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -5.5
         upper limit
    1.5

    Secondary: Serum Creatinine Level

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    End point title
    Serum Creatinine Level
    End point description
    Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 milligram per deciliter (mg/dL) for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.
    End point type
    Secondary
    End point timeframe
    Month 3, 6, 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    102 [3]
    94 [4]
    Units: mg/dL
    arithmetic mean (standard deviation)
        Month 3 (n=102, 94)
    1.4 ± 0.4
    1.4 ± 0.4
        Month 6 (n=101, 92)
    1.2 ± 0.3
    1.3 ± 0.4
        Month 12 (n=98, 91)
    1.2 ± 0.3
    1.3 ± 0.3
    Notes
    [3] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [4] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Serum Creatinine Level Month: 3
    Statistical analysis description
    One-way analysis of variance (ANOVA) was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.87 [5]
    Method
    ANOVA
    Confidence interval
    Notes
    [5] - Statistical testing was based on 5% significance level.
    Statistical analysis title
    Serum Creatinine Level Month: 6
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.381 [6]
    Method
    ANOVA
    Confidence interval
    Notes
    [6] - Statistical testing was based on 5% significance level.
    Statistical analysis title
    Serum Creatinine Level Month: 12
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.096 [7]
    Method
    ANOVA
    Confidence interval
    Notes
    [7] - Statistical testing was based on 5% significance level.

    Secondary: Creatinine Clearance

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    End point title
    Creatinine Clearance
    End point description
    Creatinine clearance (CCr) is a measure of kidney function. CCr is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 millimeters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
    End point type
    Secondary
    End point timeframe
    Month 3, 6, 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    102 [8]
    94 [9]
    Units: mL/min
    arithmetic mean (standard deviation)
        Month 3 (n=102, 94)
    64 ± 19.9
    63.9 ± 16
        Month 6 (n=101, 92)
    72.8 ± 19.3
    71.6 ± 18.3
        Month 12 (n=98, 91)
    76.4 ± 22.7
    74 ± 28.6
    Notes
    [8] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [9] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Creatinine Clearance Month:3
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.979 [10]
    Method
    ANOVA
    Confidence interval
    Notes
    [10] - Statistical testing was based on 5% significance level.
    Statistical analysis title
    Creatinine Clearance Month:12
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.518 [11]
    Method
    ANOVA
    Confidence interval
    Notes
    [11] - Statistical testing was based on 5% significance level.
    Statistical analysis title
    Creatinine Clearance Month:6
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.66 [12]
    Method
    ANOVA
    Confidence interval
    Notes
    [12] - Statistical testing was based on 5% significance level.

    Secondary: Glomerular Filtration Rate (GFR) by Nankivell Method

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    End point title
    Glomerular Filtration Rate (GFR) by Nankivell Method
    End point description
    GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR was calculated using the Nankivell formula. GFR by Nankivell equation= (6.7 per serum creatinine) plus (0.25*body weight) minus (0.5*serum urea) minus (100 per height square) plus (35 for male or 25 for female). A normal GFR is greater than (>)90 mL/min per 1.73 m^2 [mL/min/1.73 m^2], although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (<)15 mL/min/1.73 m^2 indicated kidney failure.
    End point type
    Secondary
    End point timeframe
    Month 3, 6, 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    102
    94
    Units: mL/min/1.73 m^2
    arithmetic mean (standard deviation)
        Month 3 (n=102, 94)
    59.5 ± 20.4
    58.8 ± 15.2
        Month 6 (n=101, 92)
    65.2 ± 16
    64.3 ± 19.5
        Month 12 (n=98, 91)
    67.4 ± 17.5
    67.5 ± 46.5
    Statistical analysis title
    GFR by Nankivell Method Month:3
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+Rapamune+CS v CsA+MMF+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.786 [13]
    Method
    ANOVA
    Confidence interval
    Notes
    [13] - Statistical testing was based on 5% significance level.
    Statistical analysis title
    GFR by Nankivell Method Month:6
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.738 [14]
    Method
    ANOVA
    Confidence interval
    Notes
    [14] - Statistical testing was based on 5% significance level.
    Statistical analysis title
    GFR by Nankivell Method Month:12
    Statistical analysis description
    One-way ANOVA was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    196
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.977 [15]
    Method
    ANOVA
    Confidence interval
    Notes
    [15] - Statistical testing was based on 5% significance level.

    Secondary: Incidence of Biopsy-Confirmed Acute Rejection

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    End point title
    Incidence of Biopsy-Confirmed Acute Rejection
    End point description
    Diagnosis of acute rejection was made via kidney biopsy using Banff criteria. Percentage of subjects with biopsy-confirmed acute rejection was reported.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 6
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    100 [16]
    95 [17]
    Units: percentage of subjects
        number (not applicable)
    4
    3.2
    Notes
    [16] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [17] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Incidence of Biopsy-Confirmed Acute Rejection
    Statistical analysis description
    Fisher’s exact test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.999 [18]
    Method
    Fisher exact
    Confidence interval
    Notes
    [18] - Statistical testing was based on 5% significance level.

    Secondary: Histologic Grade of First Acute Rejection

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    End point title
    Histologic Grade of First Acute Rejection
    End point description
    Diagnosis of acute rejection was made via kidney biopsy. Categorization of biopsies with suspected acute rejection was based on histological findings using updated 1997 Banff criteria. Grade 1A: cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (5-10 cells/tubular cross section), Grade 1B: with severe tubulitis (>10 cells/tubular cross section), Grade 2A: mild-moderate intimal arteritis, Grade 2B: severe intimal arteritis and Grade 3: transmural arterits and/or fibrinoid necrosis. Data is reported as percentage of subjects.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    3 [19]
    3 [20]
    Units: percentage of subjects
    number (not applicable)
        1A
    100
    66.7
        1B
    0
    33.3
    Notes
    [19] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [20] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Survived

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    End point title
    Percentage of Subjects Who Survived
    End point description
    Survival defined as subjects living with or without a functioning graft.
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    98 [21]
    96 [22]
    Units: percentage of subjects
        number (not applicable)
    98
    94.8
    Notes
    [21] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [22] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Analysis of premature elimination
    Statistical analysis description
    Fisher’s exact test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.276 [23]
    Method
    Fisher exact
    Confidence interval
    Notes
    [23] - Statistical testing was based on 5% significance level.

    Secondary: Percentage of Subjects With Graft Survival

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    End point title
    Percentage of Subjects With Graft Survival
    End point description
    Graft survival defined as those subjects who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    102 [24]
    97 [25]
    Units: percentage of subjects
        number (not applicable)
    94.1
    93.8
    Notes
    [24] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [25] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Analysis of Graft Survival
    Statistical analysis description
    Fisher’s exact test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.999 [26]
    Method
    Fisher exact
    Confidence interval
    Notes
    [26] - Statistical testing was based on 5% significance level.

    Secondary: Incidence of Presumptive or Documented Infection

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    End point title
    Incidence of Presumptive or Documented Infection
    End point description
    Presumptive or documented infection during the 12 months after transplantation; was confirmed by culture, biopsy, or serology and reported. Percentage of subjects with presumptive or documented infection was reported.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    123 [27]
    118 [28]
    Units: percentage of subjects
        number (not applicable)
    20.3
    18.6
    Notes
    [27] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [28] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Incidence of Presumptive or Documented Infection
    Statistical analysis description
    Chi-square test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.868 [29]
    Method
    Chi-squared
    Confidence interval
    Notes
    [29] - Statistical testing was based on 5% significance level.

    Secondary: Incidence of Histologically Confirmed Lymphoproliferative Disease

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    End point title
    Incidence of Histologically Confirmed Lymphoproliferative Disease
    End point description
    Lymphoproliferative disorder represents an abnormal proliferation of B cells in response to either primary or reactivated infection with Epstein-Barr virus. Percentage of subjects with histologically confirmed lymphoproliferative disease was reported.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    97 [30]
    91 [31]
    Units: percentage of subjects
        number (not applicable)
    1
    0
    Notes
    [30] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [31] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Analysis of efficacy failure
    Statistical analysis description
    Fisher’s exact test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.999 [32]
    Method
    Fisher exact
    Confidence interval
    Notes
    [32] - Statistical testing was based on 5% significance level.

    Secondary: Percentage of Subjects with Efficacy Failure or Premature Elimination

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    End point title
    Percentage of Subjects with Efficacy Failure or Premature Elimination
    End point description
    Efficacy failure was defined as the first occurrence of acute rejection, graft loss, or death. Premature elimination was defined as elimination from the study for any other reason.
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    123 [33]
    118 [34]
    Units: percentage of subjects
        number (not applicable)
    22
    22.9
    Notes
    [33] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [34] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Analysis of efficacy failure
    Statistical analysis description
    Chi-square test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.985 [35]
    Method
    Chi-squared
    Confidence interval
    Notes
    [35] - Statistical testing was based on 5% significance level.

    Secondary: Incidence of Anemia

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    End point title
    Incidence of Anemia
    End point description
    Diagnostic criterion for anemia was based on the laboratory results; in men: hemoglobin (Hb) <14 gram per deciliter (g/dL), hematocrit (Hct) <42%, or red blood cells (RBCs) <4.5 million/liter (million/L); for women: Hb <12 g/dL, Hct <37%, or RBC < 4 million/L. Percentage of subjects with anaemia was reported.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    123 [36]
    118 [37]
    Units: percentage of subjects
        number (not applicable)
    94.3
    98.3
    Notes
    [36] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    [37] - N=(number of subjects analyzed)signifies those subjects who were evaluable for this outcome measure.
    Statistical analysis title
    Analysis for Incidence of Anemia
    Statistical analysis description
    Fisher’s exact test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.172 [38]
    Method
    Fisher exact
    Confidence interval
    Notes
    [38] - Statistical testing was based on 5% significance level.

    Secondary: Number of Subjects Who Discontinued

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    End point title
    Number of Subjects Who Discontinued
    End point description
    Number of subjects who discontinued the study treatment due to any reason is reported.
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    CsA+Rapamune+CS CsA+MMF+CS
    Number of subjects analysed
    125
    120
    Units: subjects
        number (not applicable)
    29
    29
    Statistical analysis title
    Analysis of Subjects Who Discontinued
    Statistical analysis description
    Chi-square test was used to test the difference.
    Comparison groups
    CsA+MMF+CS v CsA+Rapamune+CS
    Number of subjects included in analysis
    245
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.978 [39]
    Method
    Chi-squared
    Confidence interval
    Notes
    [39] - Statistical testing was based on 5% significance level.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events are reported from time of first dose of study treatment up to 9999 days after last dose of study treatment .
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    CsA+RAPAMUNE+CS
    Reporting group description
    Enter Description here

    Reporting group title
    CsA+MMF+CS
    Reporting group description
    Enter Description here

    Serious adverse events
    CsA+RAPAMUNE+CS CsA+MMF+CS
    Total subjects affected by serious adverse events
         subjects affected / exposed
    56 / 125 (44.80%)
    44 / 120 (36.67%)
         number of deaths (all causes)
    2
    5
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial thrombosis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    13 / 125 (10.40%)
    10 / 120 (8.33%)
         occurrences causally related to treatment / all
    8 / 13
    5 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Impaired healing
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Postoperative wound complication
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney rupture
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    8 / 125 (6.40%)
    4 / 120 (3.33%)
         occurrences causally related to treatment / all
    3 / 8
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    17 / 125 (13.60%)
    5 / 120 (4.17%)
         occurrences causally related to treatment / all
    12 / 17
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus test positive
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipids increased
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute myocardial infarction
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Aplasia pure red cell
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    4 / 125 (3.20%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic uraemic syndrome
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    4 / 125 (3.20%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Diabetic neuropathy
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 125 (0.00%)
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphthous stomatitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal artery thrombosis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperoxaluria
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteral necrosis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    3 / 125 (2.40%)
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 125 (0.80%)
    7 / 120 (5.83%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Candida infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus urinary tract infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 125 (3.20%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    2 / 125 (1.60%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    2 / 125 (1.60%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Penile infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 125 (0.80%)
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    7 / 125 (5.60%)
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    2 / 125 (1.60%)
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection bacterial
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 125 (0.80%)
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    CsA+RAPAMUNE+CS CsA+MMF+CS
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    67 / 125 (53.60%)
    44 / 120 (36.67%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Lymphocele
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    2 / 125 (1.60%)
    1 / 120 (0.83%)
         occurrences all number
    2
    1
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Oedema
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Impaired healing
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Seroma
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Postoperative wound complication
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Toxicity to various agents
         subjects affected / exposed
    3 / 125 (2.40%)
    1 / 120 (0.83%)
         occurrences all number
    3
    1
    Wound dehiscence
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Wrist fracture
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences all number
    1
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 125 (5.60%)
    4 / 120 (3.33%)
         occurrences all number
    7
    4
    Blood cholesterol increased
         subjects affected / exposed
    11 / 125 (8.80%)
    3 / 120 (2.50%)
         occurrences all number
    11
    3
    Blood triglycerides increased
         subjects affected / exposed
    15 / 125 (12.00%)
    5 / 120 (4.17%)
         occurrences all number
    15
    5
    Cytomegalovirus test positive
         subjects affected / exposed
    2 / 125 (1.60%)
    4 / 120 (3.33%)
         occurrences all number
    2
    4
    Blood glucose increased
         subjects affected / exposed
    6 / 125 (4.80%)
    5 / 120 (4.17%)
         occurrences all number
    6
    5
    Drug level increased
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Blood creatinine increased
         subjects affected / exposed
    4 / 125 (3.20%)
    6 / 120 (5.00%)
         occurrences all number
    4
    6
    Platelet count decreased
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences all number
    1
    1
    Liver function test abnormal
         subjects affected / exposed
    21 / 125 (16.80%)
    8 / 120 (6.67%)
         occurrences all number
    21
    8
    Lipids increased
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Immunosuppressant drug level increased
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    6 / 125 (4.80%)
    6 / 120 (5.00%)
         occurrences all number
    6
    6
    White blood cell count decreased
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 120 (1.67%)
         occurrences all number
    0
    2
    Thrombocytopenia
         subjects affected / exposed
    7 / 125 (5.60%)
    0 / 120 (0.00%)
         occurrences all number
    7
    0
    Leukopenia
         subjects affected / exposed
    5 / 125 (4.00%)
    3 / 120 (2.50%)
         occurrences all number
    5
    3
    Thrombocytopenic purpura
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Aphthous stomatitis
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Diarrhoea
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Oral disorder
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Pancreatitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Renal vein thrombosis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Renal tubular necrosis
         subjects affected / exposed
    3 / 125 (2.40%)
    2 / 120 (1.67%)
         occurrences all number
    3
    2
    Nocturia
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Nephrolithiasis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Osteonecrosis
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 120 (0.00%)
         occurrences all number
    2
    0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 120 (1.67%)
         occurrences all number
    0
    2
    Diabetes mellitus
         subjects affected / exposed
    0 / 125 (0.00%)
    3 / 120 (2.50%)
         occurrences all number
    0
    3
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Herpes simplex
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Fungal infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 125 (0.00%)
    3 / 120 (2.50%)
         occurrences all number
    0
    3
    Cystitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 120 (0.83%)
         occurrences all number
    1
    1
    Candida infection
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 125 (3.20%)
    5 / 120 (4.17%)
         occurrences all number
    4
    5
    Oral infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 120 (0.83%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 120 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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