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    Clinical Trial Results:
    Randomized Multicenter Trial Comparing Valganciclovir CMV Prophylaxis Versus Pre-emptive Therapy after Renal Transplantation Using Proteomics for Monitoring of Graft Alteration

    Summary
    EudraCT number
    2005-004695-20
    Trial protocol
    DE   AT  
    Global end of trial date
    26 Oct 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    22 Apr 2017
    First version publication date
    22 Apr 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ML19313
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00372229
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Oct 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Oct 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the incidence of cytomegalovirus (CMV) disease and corresponding renal graft alteration.
    Protection of trial subjects
    All study subjects were required to read and sign an informed consent form.
    Background therapy
    Subjects received immunosuppression with a calcineurin inhibitor (CNI; (cyclosporine A or tacrolimus), mycophenolate mofetil (MMF) and steroids, with dosing according to study center practice.
    Evidence for comparator
    -
    Actual start date of recruitment
    31 May 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    7 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 23
    Country: Number of subjects enrolled
    Germany: 276
    Worldwide total number of subjects
    299
    EEA total number of subjects
    299
    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)
    0
    Adults (18-64 years)
    234
    From 65 to 84 years
    65
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    342 subjects were screened, and 43 subjects were not randomized. Central randomization stratified by study center and by induction immunosuppression with polyclonal antibodies, such as such as anti- thymocyte globuline (ATG), anti-lymphocyte globulin (ALG), or Muromonab-CD3 was performed.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Valganciclovir CMV Prophylaxis
    Arm description
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.
    Arm type
    Experimental

    Investigational medicinal product name
    Valganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

    Arm title
    Pre-emptive CMV Therapy
    Arm description
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.
    Arm type
    Experimental

    Investigational medicinal product name
    Valganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function.

    Investigational medicinal product name
    Ganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.

    Number of subjects in period 1
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Started
    148
    151
    Completed
    117
    122
    Not completed
    31
    29
         Graft loss
    -
    3
         Consent withdrawn
    16
    14
         Refused treatment/did not cooperate
    3
    1
         Protocol voilation
    3
    4
         Subject died
    3
    2
         Reason not specified
    3
    2
         Lost to follow-up
    3
    3
    Period 2
    Period 2 title
    Follow-Up Phase
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Valganciclovir CMV Prophylaxis (Follow-Up)
    Arm description
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.
    Arm type
    Experimental

    Investigational medicinal product name
    Valganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

    Arm title
    Pre-emptive CMV Therapy (Follow-Up)
    Arm description
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.
    Arm type
    Experimental

    Investigational medicinal product name
    Valganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function.

    Investigational medicinal product name
    Ganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.

    Number of subjects in period 2
    Valganciclovir CMV Prophylaxis (Follow-Up) Pre-emptive CMV Therapy (Follow-Up)
    Started
    117
    122
    Completed
    71
    70
    Not completed
    46
    52
         Graft loss
    8
    7
         Consent withdrawn
    13
    19
         Refused treatment/did not cooperate
    -
    1
         Adverse event/intercurrent illness
    1
    -
         Subject died
    9
    12
         Administrative
    1
    -
         Lost to follow-up
    12
    10
         Reason not specified
    2
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Valganciclovir CMV Prophylaxis
    Reporting group description
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

    Reporting group title
    Pre-emptive CMV Therapy
    Reporting group description
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.

    Reporting group values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy Total
    Number of subjects
    148 151 299
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    51.18 ± 13.463 54.24 ± 11.906 -
    Gender categorical
    Units: Subjects
        Female
    45 55 100
        Male
    103 96 199

    End points

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    End points reporting groups
    Reporting group title
    Valganciclovir CMV Prophylaxis
    Reporting group description
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

    Reporting group title
    Pre-emptive CMV Therapy
    Reporting group description
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.
    Reporting group title
    Valganciclovir CMV Prophylaxis (Follow-Up)
    Reporting group description
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

    Reporting group title
    Pre-emptive CMV Therapy (Follow-Up)
    Reporting group description
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.

    Primary: Percentage of Subjects with Active Cytomegalovirus (CMV) Infection Within 12 Months

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    End point title
    Percentage of Subjects with Active Cytomegalovirus (CMV) Infection Within 12 Months
    End point description
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Primary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (confidence interval 96%)
    14.1 (7 to 21.1)
    42.6 (33.9 to 51.3)
    Statistical analysis title
    Valganciclovir CMV Proph./Pre-emptive CMV Therapy
    Comparison groups
    Valganciclovir CMV Prophylaxis v Pre-emptive CMV Therapy
    Number of subjects included in analysis
    299
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference
    Point estimate
    -28.5
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -39.7
         upper limit
    -17.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.45

    Primary: Percentage of Subjects with CMV Disease Within 12 months Including CMV Syndrome and Tissue Invasive Disease

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    End point title
    Percentage of Subjects with CMV Disease Within 12 months Including CMV Syndrome and Tissue Invasive Disease
    End point description
    CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. Intent-to-treat (ITT) population.
    End point type
    Primary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (confidence interval 96%)
    5.6 (1.4 to 9.8)
    16.9 (10.3 to 23.6)
    Statistical analysis title
    Valganciclovir CMV Proph./Pre-emptive CMV Therapy
    Comparison groups
    Valganciclovir CMV Prophylaxis v Pre-emptive CMV Therapy
    Number of subjects included in analysis
    299
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference
    Point estimate
    -11.3
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -19.2
         upper limit
    -3.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.83

    Primary: Urine Proteomic Pattern at Month 12

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    End point title
    Urine Proteomic Pattern at Month 12
    End point description
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. Urine proteomic pattern was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Primary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: nephropathy index
        least squares mean (standard error)
    -0.1057 ± 0.1538
    0.1452 ± 0.1006
    Statistical analysis title
    Valganciclovir CMV Proph./Pre-emptive CMV Therapy
    Comparison groups
    Valganciclovir CMV Prophylaxis v Pre-emptive CMV Therapy
    Number of subjects included in analysis
    299
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.1739
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.2509
    Confidence interval
         level
    99%
         sides
    2-sided
         lower limit
    -0.2271
         upper limit
    0.7289
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1838

    Primary: Percentage of Subjects With Graft Loss at Month 84

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    End point title
    Percentage of Subjects With Graft Loss at Month 84 [1]
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Primary
    End point timeframe
    Up to 84 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analysis only.
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (not applicable)
    7.43
    8.61
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with CMV Syndrome Within 12 Months

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    End point title
    Percentage of Subjects with CMV Syndrome Within 12 Months
    End point description
    CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (confidence interval 95%)
    5.6 (1.6 to 9.7)
    14.6 (8.7 to 20.6)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with CMV Tissue Invasive Disease Within 12 Months

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    End point title
    Percentage of Subjects with CMV Tissue Invasive Disease Within 12 Months
    End point description
    CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (confidence interval 95%)
    3.3 (0.1 to 6.4)
    3.6 (0.5 to 6.8)
    No statistical analyses for this end point

    Secondary: Time to Occurrence of First Viremia Within 12 Months

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    End point title
    Time to Occurrence of First Viremia Within 12 Months
    End point description
    Viremia was defined as plasma PCR ≥ 400 copies/ml. The intent-to-treat (ITT) population included all randomized subjects. Here, 99999 indicates not calculable.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148 [2]
    151 [3]
    Units: days
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (160 to 99999)
    Notes
    [2] - Median and confidence limits were not reached.
    [3] - Median and upper confidence limit were not reached.
    No statistical analyses for this end point

    Secondary: Viral Burden at Viremia

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    End point title
    Viral Burden at Viremia
    End point description
    Time-weighted area under the curve (AUC) of the polymerase chain reaction (PCR). Viremia was defined as plasma PCR ≥ 400 copies/ml. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: copies/ml*days
        arithmetic mean (standard deviation)
    5309.83 ± 14355.836
    3765.8 ± 8480.521
    No statistical analyses for this end point

    Secondary: Creatinine Clearance at Month 12

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    End point title
    Creatinine Clearance at Month 12
    End point description
    Creatinine clearance was estimated using the Cockcroft-Gault-formula. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: millilitre(s)/minute
        arithmetic mean (standard deviation)
    61.1 ± 23.3
    61.3 ± 22.24
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with at Least One Treated and Biopsy-Proven Acute Rejection Episode Within 12 Months

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    End point title
    Percentage of Subjects with at Least One Treated and Biopsy-Proven Acute Rejection Episode Within 12 Months
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (not applicable)
    18.2
    13.2
    No statistical analyses for this end point

    Secondary: Days of Hospitalization

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    End point title
    Days of Hospitalization
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: days
        median (full range (min-max))
    26.5 (0 to 258)
    32 (0 to 221)
    No statistical analyses for this end point

    Secondary: Relationship Between Proteomics Pattern and Graft Survival

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    End point title
    Relationship Between Proteomics Pattern and Graft Survival
    End point description
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273, CMV, and nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. The intent-to-treat (ITT) population included all randomized subjects. Only subjects with data were included in the analysis. Here, 99999 indicates not calculable.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: score on a scale
    arithmetic mean (standard deviation)
        CKD273:Visit 6: With Graft Loss (n=1, 4)
    0.4 ± 99999
    0.8 ± 0.2944
        CKD273:Visit 6: Without Graft Loss (n=112, 110)
    0.371 ± 0.3578
    0.379 ± 0.3499
        CKD273:Visit 13: With Graft Loss (n=0, 1)
    99999 ± 99999
    0.5 ± 99999
        CKD273:Visit 13: Without Graft Loss (n=102, 109)
    0.258 ± 0.3719
    0.293 ± 0.3648
        CKD273:Visit 15: With Graft Loss (n=2, 0)
    0.6 ± 0.5657
    99999 ± 99999
        CKD273:Visit 15: Without Graft Loss (n=104, 102)
    0.27 ± 0.3793
    0.326 ± 0.3618
        CMV:Visit 6: With Graft Loss (n=1, 4)
    -0.5 ± 99999
    -0.3 ± 0.7616
        CMV:Visit 6: Without Graft Loss (n=112, 110)
    0 ± 0.9535
    -0.007 ± 0.8984
        CMV:Visit 13: With Graft Loss (n=0, 1)
    99999 ± 99999
    -0.3 ± 99999
        CMV:Visit 13: Without Graft Loss (n=102, 109)
    0.036 ± 0.7976
    -0.048 ± 0.7614
        CMV:Visit 15: With Graft Loss (n=2, 0)
    0.1 ± 0.7071
    99999 ± 99999
        CMV:Visit 15: Without Graft Loss (n=104, 102)
    -0.076 ± 0.6922
    -0.068 ± 0.7081
        Nephropathy:Visit 6: With Graft Loss (n=1, 4)
    0.5 ± 99999
    1.1 ± 0.9933
        Nephropathy:Visit 6:Without Graft Loss (n=112,110)
    0.107 ± 1.1784
    0.086 ± 1.0489
        Visit 13: With Graft Loss (n=0, 1)
    99999 ± 99999
    -0.8 ± 99999
        Nephropathy:Visit 13:Without Graft Loss(n=102,109)
    -0.05 ± 1.0624
    0.008 ± 1.0848
        Nephropathy:Visit 15: With Graft Loss (n=2, 0)
    1.35 ± 2.8991
    99999 ± 99999
        Nephropathy:Visit15: Without Graft Loss(n=104,102)
    -0.007 ± 0.8535
    0.102 ± 1.1221
    No statistical analyses for this end point

    Secondary: Relationship Between Proteomics Pattern and Subject Survival

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    End point title
    Relationship Between Proteomics Pattern and Subject Survival
    End point description
    The intent-to-treat (ITT) population included all randomized subjects. Only subjects with data were included in the analysis. Here, 99999 indicates not calculable.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: score on a scale
    arithmetic mean (standard deviation)
        CKD273:Visit 6: Did not Survive (n=2, 1)
    0.4 ± 0.1414
    0.5 ± 99999
        CKD273:Visit 6: Survived (n=111, 113)
    0.371 ± 0.3591
    0.393 ± 0.357
        CKD273:Visit 13: Did not Survive (n=1, 1)
    0.7 ± 99999
    0.5 ± 99999
        CKD273:Visit 13: Survived (n=101, 109)
    0.253 ± 0.3711
    0.293 ± 0.3648
        CKD273:Visit 15: Did not Survive (n=0, 0)
    99999 ± 99999
    99999 ± 99999
        CKD273:Visit 15: Survived (n=106, 102)
    0.276 ± 0.3824
    0.326 ± 0.3618
        CMV:Visit 6: Did not Survive (n=2, 1)
    1.15 ± 1.3435
    -0.9 ± 99999
        CMV:Visit 6: Survived (n=111, 113)
    -0.025 ± 0.9374
    -0.01 ± 0.8927
        CMV:Visit 13: Did not Survive (n=1, 1)
    0.4 ± 99999
    -0.3 ± 99999
        CMV:Visit 13: Survived (n=101, 109)
    0.033 ± 0.8008
    -0.048 ± 0.7614
        CMV:Visit 15: Did not Survive (n=0, 0)
    99999 ± 99999
    99999 ± 99999
        CMV:Visit 15: Survived (n=106, 102)
    -0.073 ± 0.6894
    -0.068 ± 0.7081
        Nephropathy:Visit 6: Did not Survive (n=2, 1)
    0.15 ± 0.0707
    -0.1 ± 99999
        Nephropathy:Visit 6: Survived (n=111, 113)
    0.101 ± 1.1851
    0.124 ± 1.064
        Nephropathy:Visit 13: Did not Survive (n=1, 1)
    1.8 ± 99999
    -0.8 ± 99999
        Nephropathy:Visit 13: Survived (n=101, 109)
    -0.068 ± 1.0514
    0.008 ± 1.0848
        Nephropathy:Visit 15: Did not Survive (n=0, 0)
    99999 ± 99999
    99999 ± 99999
        Nephropathy:Visit 15: Survived (n=106, 102)
    0.019 ± 0.9105
    0.102 ± 1.1221
    No statistical analyses for this end point

    Secondary: Proteomics Parameter: CKD273

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    End point title
    Proteomics Parameter: CKD273
    End point description
    The proteomics of CKD273 was measured on a scale between –1, indicating no graft alteration, and +1, indicating graft alteration. The intent-to-treat (ITT) population included all randomized subjects. Only subjects with data were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: score on a scale
    arithmetic mean (standard deviation)
        Visit 6 (n=113, 114)
    0.372 ± 0.3562
    0.394 ± 0.3556
        Visit 13 (n=102, 110)
    0.258 ± 0.3719
    0.295 ± 0.3637
        Visit 15 (n=106, 102)
    0.276 ± 0.3824
    0.326 ± 0.3618
    No statistical analyses for this end point

    Secondary: Proteomics Parameter: CMV

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    End point title
    Proteomics Parameter: CMV
    End point description
    The proteomics of CMV was measured on a scale between –1, indicating no graft alteration, and +1, indicating graft alteration. The intent-to-treat (ITT) population included all randomized subjects. Only subjects with data were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: score on a scale
    arithmetic mean (standard deviation)
        Visit 6 (n=113, 114)
    -0.004 ± 0.9504
    -0.018 ± 0.8927
        Visit 13 (n=102, 110)
    0.036 ± 0.7976
    -0.05 ± 0.7583
        Visit 15 (n=106, 102)
    -0.073 ± 0.6894
    -0.068 ± 0.7081
    No statistical analyses for this end point

    Secondary: Proteomics Parameter: Nephropathy

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    End point title
    Proteomics Parameter: Nephropathy
    End point description
    The proteomics of nephropathy was measured on a scale between –1, indicating no graft alteration, and +1, indicating graft alteration. The intent-to-treat (ITT) population included all randomized subjects. Only subjects with data were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: score on a scale
    arithmetic mean (standard deviation)
        Visit 6 (n=113, 114)
    0.102 ± 1.1745
    0.122 ± 1.0595
        Visit 13 (n=102, 110)
    -0.05 ± 1.0624
    0.001 ± 1.0826
        Visit 15 (n=106, 102)
    0.019 ± 0.9105
    0.102 ± 1.1221
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Surviving at Month 12

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    End point title
    Percentage of Subjects Surviving at Month 12
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (not applicable)
    98
    98.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Graft Survival at Month 12

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    End point title
    Percentage of Subjects with Graft Survival at Month 12
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (not applicable)
    98.6
    96
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Leukopenia and Neutropenia Within 12 Months

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    End point title
    Percentage of Subjects with Leukopenia and Neutropenia Within 12 Months
    End point description
    Leukopenia: white blood cell (WBC) of < 3,500/microlitre (μL) and < 1,000/μL. Neutropenia: absolute neutrophil count (ANC) < 750/μL within 12 months. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
    number (not applicable)
        Percentage of subjects with leukopenia
    35.1
    26.5
        Percentage of subjects with neutropenia
    16.9
    12.6
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Any Opportunistic Infection Within 12 Months

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    End point title
    Percentage of Subjects with Any Opportunistic Infection Within 12 Months
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
        number (not applicable)
    31.1
    37.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Post-Transplant Diabetes Mellitus

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    End point title
    Percentage of Subjects with Post-Transplant Diabetes Mellitus
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
    number (not applicable)
        Month 6
    2.7
    1.3
        Month 12
    3.4
    0.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Active CMV Infections not Responding to Valganciclovir or IV Ganciclovir Treatment

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    End point title
    Percentage of Subjects with Active CMV Infections not Responding to Valganciclovir or IV Ganciclovir Treatment
    End point description
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/milliliter (ml). The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    17 [4]
    82 [5]
    Units: percentage of subjects
        number (not applicable)
    11.8
    18.3
    Notes
    [4] - Only subjects with data were included in the analysis.
    [5] - Only subjects with data were included in the analysis.
    No statistical analyses for this end point

    Secondary: Number of Subjects with CMV Viremia (Active CMV Infection) from Baseline to Month 24 and every 12 Months up to Month 84

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    End point title
    Number of Subjects with CMV Viremia (Active CMV Infection) from Baseline to Month 24 and every 12 Months up to Month 84
    End point description
    Viremia (active CMV Infection) was defined as PCR ≥ 400 copies/ml. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    16
    59
        36 months
    16
    59
        48 months
    16
    59
        60 months
    16
    59
        72 months
    17
    60
        84 months
    17
    60
    No statistical analyses for this end point

    Secondary: Number of Subjects with CMV Disease from Baseline to Month 24 and every 12 Months up to Month 84

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    End point title
    Number of Subjects with CMV Disease from Baseline to Month 24 and every 12 Months up to Month 84
    End point description
    CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. Intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    7
    23
        36 months
    7
    23
        48 months
    7
    23
        60 months
    7
    24
        72 months
    7
    24
        84 months
    7
    24
    No statistical analyses for this end point

    Secondary: Number of Subjects with CMV Syndrome from Baseline to Month 24 and every 12 Months up to Month 84

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    End point title
    Number of Subjects with CMV Syndrome from Baseline to Month 24 and every 12 Months up to Month 84
    End point description
    CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    7
    20
        36 months
    7
    20
        48 months
    7
    20
        60 months
    7
    21
        72 months
    7
    21
        84 months
    7
    21
    No statistical analyses for this end point

    Secondary: Number of Subjects with CMV Tissue Invasive Disease from Baseline to Month 24 and every 12 Months up to Month 84

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    End point title
    Number of Subjects with CMV Tissue Invasive Disease from Baseline to Month 24 and every 12 Months up to Month 84
    End point description
    CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    4
    5
        36 months
    4
    5
        48 months
    4
    5
        60 months
    4
    5
        72 months
    4
    5
        84 months
    4
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects with Active CMV Infection after Month 24 and every 12 Months up to Month 84

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    End point title
    Number of Subjects with Active CMV Infection after Month 24 and every 12 Months up to Month 84
    End point description
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/milliliter (ml). The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    16
    59
        36 months
    16
    59
        48 months
    16
    59
        60 months
    16
    59
        72 months
    17
    60
        84 months
    17
    60
    No statistical analyses for this end point

    Secondary: Number of Subjects with CMV Disease after Month 24 and every 12 Months up to Month 84

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    End point title
    Number of Subjects with CMV Disease after Month 24 and every 12 Months up to Month 84
    End point description
    CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. Intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    7
    23
        36 months
    7
    23
        48 months
    7
    23
        60 months
    7
    24
        72 months
    7
    24
        84 months
    7
    24
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Surviving at Month 24 and every 12 Months up to Month 84

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    End point title
    Percentage of Subjects Surviving at Month 24 and every 12 Months up to Month 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
    number (not applicable)
        24 months
    97.97
    94.7
        36 months
    95.95
    94.04
        48 months
    94.59
    93.38
        60 months
    92.57
    92.05
        72 months
    90.54
    89.4
        84 months
    90.54
    88.74
    No statistical analyses for this end point

    Secondary: Number of Subjects who Died from Month 24 to Month 84

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    End point title
    Number of Subjects who Died from Month 24 to Month 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    3
    8
        36 months
    6
    9
        48 months
    8
    10
        60 months
    11
    12
        72 months
    14
    16
        84 months
    14
    17
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Graft Survival at Month 24 and Every 12 Months up to Month 84

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    End point title
    Percentage of Subjects with Graft Survival at Month 24 and Every 12 Months up to Month 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
    number (not applicable)
        24 months
    97.3
    94.7
        36 months
    97.3
    93.38
        48 months
    96.62
    93.38
        60 months
    95.95
    92.05
        72 months
    94.59
    91.39
        84 months
    92.57
    91.39
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Had Lost Their Transplant from Months 24 to 84

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    End point title
    Number of Subjects Who Had Lost Their Transplant from Months 24 to 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    4
    8
        36 months
    4
    10
        48 months
    5
    10
        60 months
    6
    12
        72 months
    8
    13
        84 months
    11
    13
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Graft Loss (with and without CMV Infection) at Month 84

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    End point title
    Percentage of Subjects with Graft Loss (with and without CMV Infection) at Month 84
    End point description
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to 84 months
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
    number (confidence interval 95%)
        Subjects with CMV infection (n = 77)
    8.3 (0 to 24)
    17.9 (7.2 to 28.6)
        Subjects without CMV infection (n = 222)
    11.5 (4.7 to 18.4)
    5.8 (0.1 to 11.6)
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Had Lost Their Transplant or Died From Months 24 to 84

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    End point title
    Number of Subjects Who Had Lost Their Transplant or Died From Months 24 to 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: subjects
        24 months
    7
    15
        36 months
    9
    18
        48 months
    12
    19
        60 months
    16
    23
        72 months
    21
    28
        84 months
    24
    29
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Graft Survival or Subject Survival at Month 24 and Every 12 Months up to Month 84

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    End point title
    Percentage of Subjects with Graft Survival or Subject Survival at Month 24 and Every 12 Months up to Month 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: percentage of subjects
    number (not applicable)
        24 months
    95.27
    90.07
        36 months
    93.92
    88.08
        48 months
    91.89
    87.42
        60 months
    89.19
    84.77
        72 months
    85.81
    81.46
        84 months
    83.78
    80.79
    No statistical analyses for this end point

    Secondary: Number of Graft Rejections from Months 24 to Month 84

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    End point title
    Number of Graft Rejections from Months 24 to Month 84
    End point description
    The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: graft rejections
        24 months
    39
    48
        36 months
    42
    51
        48 months
    45
    51
        60 months
    46
    52
        72 months
    48
    53
        84 months
    48
    53
    No statistical analyses for this end point

    Secondary: Creatinine Clearance at Month 24 and every 12 Months up to Month 84

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    End point title
    Creatinine Clearance at Month 24 and every 12 Months up to Month 84
    End point description
    Creatinine Clearance estimated by Cockcroft-Gault formula. The intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Month 24 to Month 84
    End point values
    Valganciclovir CMV Prophylaxis Pre-emptive CMV Therapy
    Number of subjects analysed
    148
    151
    Units: millimitres/minute
    arithmetic mean (standard deviation)
        24 months
    63.2 ± 23.85
    62.9 ± 25.01
        36 months
    63.9 ± 24.14
    64.5 ± 25.33
        48 months
    63.1 ± 23.81
    62.6 ± 24.63
        60 months
    62.2 ± 22.58
    64.9 ± 27.85
        72 months
    63.3 ± 28.98
    64.7 ± 27.25
        84 months
    59.5 ± 26.76
    60.8 ± 25.39
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 7 years
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    12.0
    Reporting groups
    Reporting group title
    Pre-emptive CMV Therapy
    Reporting group description
    If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site’s standard, instead of valganciclovir.

    Reporting group title
    Valganciclovir CMV Prophylaxis
    Reporting group description
    900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

    Serious adverse events
    Pre-emptive CMV Therapy Valganciclovir CMV Prophylaxis
    Total subjects affected by serious adverse events
         subjects affected / exposed
    96 / 151 (63.58%)
    94 / 148 (63.51%)
         number of deaths (all causes)
    17
    14
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Arterial occlusive disease
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         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
    1 / 151 (0.66%)
    4 / 148 (2.70%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    4 / 151 (2.65%)
    6 / 148 (4.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 151 (0.66%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Arteriovenous fistula operation
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary arterial stent insertion
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatectomy
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Removal of ambulatory peritoneal catheter
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteral stent removal
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric operation
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiosarcoma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Kidney transplant rejection
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Impaired healing
         subjects affected / exposed
    3 / 151 (1.99%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 151 (1.32%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal oedema
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (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
    Abdominal wound dehiscence
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site complication
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    1 / 151 (0.66%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft complication
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    2 / 151 (1.32%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft dysfunction
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirenal haematoma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt blood flow excessive
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant failure
         subjects affected / exposed
    0 / 151 (0.00%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric anastomosis complication
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary anastomotic leak
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood calcium increased
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine abnormal
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    17 / 151 (11.26%)
    23 / 148 (15.54%)
         occurrences causally related to treatment / all
    0 / 18
    1 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose abnormal
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood parathyroid hormone increased
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    0 / 151 (0.00%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urine output decreased
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trifascicular block
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Congenital cystic kidney disease
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         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
    Atelectasis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphonia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea at rest
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 151 (1.99%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 151 (0.00%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrogenic anaemia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Benign intracranial hypertension
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Charles Bonnet syndrome
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Cupulolithiasis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deafness unilateral
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 151 (3.31%)
    6 / 148 (4.05%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis intestinal haemorrhagic
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flatulence
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 151 (0.66%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia, obstructive
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sclerosing encapsulating peritonitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Focal segmental glomerulosclerosis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postrenal failure
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    1 / 151 (0.66%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    3 / 151 (1.99%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 151 (0.66%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteral necrosis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         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
    2 / 151 (1.32%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary fistula
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    3 / 151 (1.99%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Osteoarthritis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 151 (0.66%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    2 / 151 (1.32%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes with hyperosmolarity
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess oral
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis staphylococcal
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    2 / 151 (1.32%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft infection
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 151 (0.66%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected lymphocele
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 151 (3.97%)
    6 / 148 (4.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia escherichia
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia primary atypical
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 151 (1.32%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal abscess
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    13 / 151 (8.61%)
    9 / 148 (6.08%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    7 / 151 (4.64%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound abscess
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Pre-emptive CMV Therapy Valganciclovir CMV Prophylaxis
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    140 / 151 (92.72%)
    139 / 148 (93.92%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    37 / 151 (24.50%)
    30 / 148 (20.27%)
         occurrences all number
    41
    33
    Hypotension
         subjects affected / exposed
    9 / 151 (5.96%)
    7 / 148 (4.73%)
         occurrences all number
    10
    8
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    11 / 151 (7.28%)
    5 / 148 (3.38%)
         occurrences all number
    11
    5
    Oedema
         subjects affected / exposed
    31 / 151 (20.53%)
    27 / 148 (18.24%)
         occurrences all number
    37
    30
    Oedema peripheral
         subjects affected / exposed
    30 / 151 (19.87%)
    34 / 148 (22.97%)
         occurrences all number
    40
    42
    Pain
         subjects affected / exposed
    11 / 151 (7.28%)
    4 / 148 (2.70%)
         occurrences all number
    20
    5
    Pyrexia
         subjects affected / exposed
    9 / 151 (5.96%)
    12 / 148 (8.11%)
         occurrences all number
    12
    21
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    14 / 151 (9.27%)
    17 / 148 (11.49%)
         occurrences all number
    15
    24
    Sleep disorder
         subjects affected / exposed
    13 / 151 (8.61%)
    9 / 148 (6.08%)
         occurrences all number
    26
    10
    Investigations
    Blood uric acid increased
         subjects affected / exposed
    7 / 151 (4.64%)
    10 / 148 (6.76%)
         occurrences all number
    7
    11
    Blood creatinine increased
         subjects affected / exposed
    21 / 151 (13.91%)
    23 / 148 (15.54%)
         occurrences all number
    25
    28
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    12 / 151 (7.95%)
    5 / 148 (3.38%)
         occurrences all number
    12
    5
    C-reactive protein increased
         subjects affected / exposed
    11 / 151 (7.28%)
    13 / 148 (8.78%)
         occurrences all number
    19
    19
    Hepatic enzyme increased
         subjects affected / exposed
    7 / 151 (4.64%)
    14 / 148 (9.46%)
         occurrences all number
    8
    17
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    38 / 151 (25.17%)
    28 / 148 (18.92%)
         occurrences all number
    45
    31
    Leukopenia
         subjects affected / exposed
    35 / 151 (23.18%)
    37 / 148 (25.00%)
         occurrences all number
    42
    47
    Leukocytosis
         subjects affected / exposed
    9 / 151 (5.96%)
    7 / 148 (4.73%)
         occurrences all number
    12
    9
    Thrombocytopenia
         subjects affected / exposed
    9 / 151 (5.96%)
    8 / 148 (5.41%)
         occurrences all number
    11
    10
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 151 (7.95%)
    23 / 148 (15.54%)
         occurrences all number
    17
    27
    Dyspnoea
         subjects affected / exposed
    12 / 151 (7.95%)
    13 / 148 (8.78%)
         occurrences all number
    17
    17
    Nervous system disorders
    Headache
         subjects affected / exposed
    14 / 151 (9.27%)
    12 / 148 (8.11%)
         occurrences all number
    18
    19
    Tremor
         subjects affected / exposed
    17 / 151 (11.26%)
    16 / 148 (10.81%)
         occurrences all number
    19
    16
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    9 / 151 (5.96%)
    3 / 148 (2.03%)
         occurrences all number
    10
    6
    Constipation
         subjects affected / exposed
    15 / 151 (9.93%)
    13 / 148 (8.78%)
         occurrences all number
    28
    14
    Diarrhoea
         subjects affected / exposed
    42 / 151 (27.81%)
    41 / 148 (27.70%)
         occurrences all number
    64
    66
    Dyspepsia
         subjects affected / exposed
    8 / 151 (5.30%)
    5 / 148 (3.38%)
         occurrences all number
    9
    9
    Nausea
         subjects affected / exposed
    16 / 151 (10.60%)
    16 / 148 (10.81%)
         occurrences all number
    26
    20
    Vomiting
         subjects affected / exposed
    9 / 151 (5.96%)
    11 / 148 (7.43%)
         occurrences all number
    13
    12
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    8 / 151 (5.30%)
    8 / 148 (5.41%)
         occurrences all number
    8
    9
    Leukocyturia
         subjects affected / exposed
    15 / 151 (9.93%)
    5 / 148 (3.38%)
         occurrences all number
    18
    6
    Proteinuria
         subjects affected / exposed
    23 / 151 (15.23%)
    18 / 148 (12.16%)
         occurrences all number
    26
    22
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    8 / 151 (5.30%)
    5 / 148 (3.38%)
         occurrences all number
    8
    5
    Pruritus
         subjects affected / exposed
    10 / 151 (6.62%)
    2 / 148 (1.35%)
         occurrences all number
    10
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    9 / 151 (5.96%)
    8 / 148 (5.41%)
         occurrences all number
    9
    8
    Back pain
         subjects affected / exposed
    7 / 151 (4.64%)
    9 / 148 (6.08%)
         occurrences all number
    7
    10
    Muscle spasms
         subjects affected / exposed
    5 / 151 (3.31%)
    13 / 148 (8.78%)
         occurrences all number
    5
    13
    Pain in extremity
         subjects affected / exposed
    16 / 151 (10.60%)
    8 / 148 (5.41%)
         occurrences all number
    28
    12
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    11 / 151 (7.28%)
    4 / 148 (2.70%)
         occurrences all number
    12
    4
    Diabetes mellitus
         subjects affected / exposed
    25 / 151 (16.56%)
    19 / 148 (12.84%)
         occurrences all number
    26
    19
    Hypercalcaemia
         subjects affected / exposed
    17 / 151 (11.26%)
    7 / 148 (4.73%)
         occurrences all number
    18
    9
    Glucose tolerance impaired
         subjects affected / exposed
    8 / 151 (5.30%)
    3 / 148 (2.03%)
         occurrences all number
    8
    3
    Hypercholesterolaemia
         subjects affected / exposed
    16 / 151 (10.60%)
    17 / 148 (11.49%)
         occurrences all number
    17
    17
    Hyperkalaemia
         subjects affected / exposed
    20 / 151 (13.25%)
    15 / 148 (10.14%)
         occurrences all number
    28
    17
    Hyperuricaemia
         subjects affected / exposed
    25 / 151 (16.56%)
    23 / 148 (15.54%)
         occurrences all number
    25
    24
    Hyperlipidaemia
         subjects affected / exposed
    23 / 151 (15.23%)
    14 / 148 (9.46%)
         occurrences all number
    24
    14
    Hypokalaemia
         subjects affected / exposed
    18 / 151 (11.92%)
    18 / 148 (12.16%)
         occurrences all number
    25
    20
    Hypocalcaemia
         subjects affected / exposed
    6 / 151 (3.97%)
    13 / 148 (8.78%)
         occurrences all number
    6
    14
    Hypophosphataemia
         subjects affected / exposed
    9 / 151 (5.96%)
    12 / 148 (8.11%)
         occurrences all number
    12
    13
    Metabolic acidosis
         subjects affected / exposed
    21 / 151 (13.91%)
    17 / 148 (11.49%)
         occurrences all number
    21
    19
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    34 / 151 (22.52%)
    36 / 148 (24.32%)
         occurrences all number
    49
    46
    Bronchitis
         subjects affected / exposed
    8 / 151 (5.30%)
    6 / 148 (4.05%)
         occurrences all number
    10
    6
    Urinary tract infection
         subjects affected / exposed
    49 / 151 (32.45%)
    53 / 148 (35.81%)
         occurrences all number
    81
    98

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 May 2006
    Protocol Amendment 1 included revised study timelines; increased number of centers from 15 to 20; changes in laboratory parameters to be measured; changes in the clinical examination at Visit 1; viral load measured at central laboratory for all centers; and an increase in the adverse event reporting period from 12 to 14 months.
    11 Apr 2008
    Protocol Amendment 2 included changes in the study timelines, recruitment period, last subject at 12 months, last subject out and total study duration; increase in the number of centers to approximately 25; changes in exclusion criteria; changes in documentation of concomitant medication; changes in CMV measurements in follow-up phase; changes in packaging and labeling; safety precautions for handling of study drug; guidance for documentation of CMV infections, rejections, opportunistic infections, and adverse events in the electronic case report form; changes in serious adverse event reporting; and inclusion of two secondary basic research projects.
    09 Aug 2010
    Protocol Amendment 3 included the following changes: for withdrawn subjects, survival of the transplant and the subject could be followed up by telephone contact, if subject gave consent, according to the German data protection law; sample for proteomics was taken only until Month 24; and removal of one of the secondary basic research projects.

    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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