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    Clinical Trial Results:
    A randomised, double-blind, active-controlled parallel group study to evaluate the effect of 52 weeks of once daily treatment of orally inhaled tiotropium + olodaterol fixed dose combination compared with tiotropium on Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with severe to very severe COPD. [DYNAGITO]

    Summary
    EudraCT number
    		 2014-002275-28
    Trial protocol
    		 FI   IT   SE   PT   DK   BE   NL   HU   GB   ES   AT   IE   LT   CZ   LV   SK   DE   SI   GR   BG   HR   PL  
    Global end of trial date
    29 Mar 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    11 Jan 2022
    First version publication date
    13 Apr 2018
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    1237.19
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02296138
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
    Public contact
    QRPE Processes and Systems Coordination, Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    QRPE Processes and Systems Coordination, Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.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
    12 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Mar 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The overall objective was to assess the effect of once daily tiotropium + olodaterol fixed-dose combination compared to 5 μg tiotropium (both delivered with the RESPIMAT inhaler) on moderate to severe COPD exacerbation in patients with severe to very severe COPD.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. If a subject continued to take trial medication, close monitoring was adhered to and all adverse events recorded.
    Background therapy
    		 -
    Evidence for comparator
    		 Approved Tiotropium inhalation solution - Respimat® inhaler
    Actual start date of recruitment
    13 Jan 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    South Africa: 118
    Country: Number of subjects enrolled
    Spain: 230
    Country: Number of subjects enrolled
    Sweden: 44
    Country: Number of subjects enrolled
    Switzerland: 34
    Country: Number of subjects enrolled
    Taiwan: 26
    Country: Number of subjects enrolled
    Thailand: 69
    Country: Number of subjects enrolled
    Turkey: 216
    Country: Number of subjects enrolled
    Ukraine: 250
    Country: Number of subjects enrolled
    United Kingdom: 65
    Country: Number of subjects enrolled
    United States: 1241
    Country: Number of subjects enrolled
    Vietnam: 41
    Country: Number of subjects enrolled
    Hong Kong: 15
    Country: Number of subjects enrolled
    Argentina: 348
    Country: Number of subjects enrolled
    Australia: 98
    Country: Number of subjects enrolled
    Austria: 61
    Country: Number of subjects enrolled
    Belgium: 63
    Country: Number of subjects enrolled
    Brazil: 173
    Country: Number of subjects enrolled
    Bulgaria: 137
    Country: Number of subjects enrolled
    Canada: 293
    Country: Number of subjects enrolled
    Chile: 40
    Country: Number of subjects enrolled
    Colombia: 30
    Country: Number of subjects enrolled
    Croatia: 50
    Country: Number of subjects enrolled
    Czechia: 152
    Country: Number of subjects enrolled
    Denmark: 85
    Country: Number of subjects enrolled
    Finland: 41
    Country: Number of subjects enrolled
    France: 95
    Country: Number of subjects enrolled
    Germany: 615
    Country: Number of subjects enrolled
    Greece: 72
    Country: Number of subjects enrolled
    Guatemala: 109
    Country: Number of subjects enrolled
    Hungary: 226
    Country: Number of subjects enrolled
    India: 336
    Country: Number of subjects enrolled
    Ireland: 23
    Country: Number of subjects enrolled
    Italy: 195
    Country: Number of subjects enrolled
    Japan: 619
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 124
    Country: Number of subjects enrolled
    Latvia: 60
    Country: Number of subjects enrolled
    Lithuania: 41
    Country: Number of subjects enrolled
    Malaysia: 52
    Country: Number of subjects enrolled
    Mexico: 60
    Country: Number of subjects enrolled
    Netherlands: 187
    Country: Number of subjects enrolled
    New Zealand: 110
    Country: Number of subjects enrolled
    Norway: 64
    Country: Number of subjects enrolled
    Philippines: 126
    Country: Number of subjects enrolled
    Poland: 528
    Country: Number of subjects enrolled
    Portugal: 82
    Country: Number of subjects enrolled
    Romania: 125
    Country: Number of subjects enrolled
    Russian Federation: 958
    Country: Number of subjects enrolled
    Serbia: 145
    Country: Number of subjects enrolled
    Singapore: 7
    Country: Number of subjects enrolled
    Slovakia: 81
    Country: Number of subjects enrolled
    Slovenia: 49
    Worldwide total number of subjects
    9009
    EEA total number of subjects
    3306
    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)
    3626
    From 65 to 84 years
    5284
    85 years and over
    99

    Subject disposition

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    Recruitment
    Recruitment details
    		 A randomised, double-blind, active-controlled parallel group study to evaluate the effect of 52 weeks of once daily treatment of orally inhaled tiotropium + olodaterol fixed dose combination compared with tiotropium on Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with severe to very severe COPD.

    Pre-assignment
    Screening details
    		 Following informed consent, the patient was entered into a maximum 7-day screening period to confirm the patient’s eligibility. At Visit 2, after a successful review of the inclusion and exclusion criteria, the patient was randomly allocated in equal ratio to receive once daily trial treatment and then entered the 360 days treatment phase.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    A randomised, double-blind, active-controlled parallel group study

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tiotropium 5 microgram (μg)
    Arm description
    		 Patient received 5 μg Tiotropium inhalation solution – RESPIMAT inhaler once daily orally for 360 days. One patient was not treated and 10 patients were found with data irregularities.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tiotropium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Oral use
    Dosage and administration details
    5 μg Tiotropium inhalation solution – RESPIMAT inhaler once daily orally for 360 days

    Arm title
    		 Tiotropium (5 μg) + Olodaterol (5 μg)
    Arm description
    		 Patient received 5 μg Tiotropium + 5 μg Olodaterol fixed-dose combination (FDC) inhalation solution – RESPIMAT inhaler once daily orally for 360 days. One patient was not treated and 11 patients were found with data irregularities.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tiotropium (5 μg) / Olodaterol (5 μg)_FDC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Oral use
    Dosage and administration details
    5 μg Tiotropium + 5 μg Olodaterol fixed-dose combination (FDC) inhalation solution – RESPIMAT inhaler once daily orally for 360 days

    Number of subjects in period 1 [1]
    		Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg)
    Started
    3941
    3939
    Completed
    3291
    3451
    Not completed
    650
    488
         Adverse event, serious fatal
    83
    82
         Consent withdrawn by subject
    184
    131
         Adverse event, non-fatal
    265
    177
         Other than specified
    15
    13
         Lost to follow-up
    9
    12
         Lack of efficacy
    59
    37
         Protocol deviation
    35
    36
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of 9009 participants that were enrolled, only 7880 received the study medication.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tiotropium 5 microgram (μg)
    Reporting group description
    		 Patient received 5 μg Tiotropium inhalation solution – RESPIMAT inhaler once daily orally for 360 days. One patient was not treated and 10 patients were found with data irregularities.

    Reporting group title
    Tiotropium (5 μg) + Olodaterol (5 μg)
    Reporting group description
    		 Patient received 5 μg Tiotropium + 5 μg Olodaterol fixed-dose combination (FDC) inhalation solution – RESPIMAT inhaler once daily orally for 360 days. One patient was not treated and 11 patients were found with data irregularities.

    Reporting group values
    		 Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg) Total
    Number of subjects
    		 3941 3939 7880
    Age categorical
    Treated set (TS): This patient set includes all randomised patients who were documented to have taken at least 1 dose of trial medication.
    Units: Subjects
    Age Continuous
    Age at the time of signing informed consent form is presented. Treated set (TS): This patient set includes all randomised patients who were documented to have taken at least 1 dose of trial medication.
    Units: years
        arithmetic mean (standard deviation)
    		 66.3 ( 8.5 ) 66.5 ( 8.4 ) -
    Sex: Female, Male
    Number of subjects is categorized as Male or Female. Treated set (TS): This patient set includes all randomised patients who were documented to have taken at least 1 dose of trial medication.
    Units: Subjects
        Female
    		 1100 1154 2254
        Male
    		 2841 2785 5626
    Race (NIH/OMB)
    Ethnicity was not captured in this trial. Treated set (TS): This patient set includes all randomised patients who were documented to have taken at least 1 dose of trial medication.
    Units: Subjects
        American Indian or Alaska Native
    		 64 77 141
        Asian
    		 607 557 1164
        Native Hawaiian or Other Pacific Islander
    		 5 3 8
        Black or African American
    		 52 58 110
        White
    		 3113 3134 6247
        More than one race
    		 20 22 42
        Unknown or Not Reported
    		 80 88 168

    End points

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    End points reporting groups
    Reporting group title
    Tiotropium 5 microgram (μg)
    Reporting group description
    		 Patient received 5 μg Tiotropium inhalation solution – RESPIMAT inhaler once daily orally for 360 days. One patient was not treated and 10 patients were found with data irregularities.

    Reporting group title
    Tiotropium (5 μg) + Olodaterol (5 μg)
    Reporting group description
    		 Patient received 5 μg Tiotropium + 5 μg Olodaterol fixed-dose combination (FDC) inhalation solution – RESPIMAT inhaler once daily orally for 360 days. One patient was not treated and 11 patients were found with data irregularities.

    Primary: Annualised rate of moderate to severe COPD exacerbations during the actual treatment period.

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    End point title
    		 Annualised rate of moderate to severe COPD exacerbations during the actual treatment period.
    End point description
    Annualised rate of moderate to severe COPD exacerbations during the actual treatment period was calculated per treatment per patient−year. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. Least Squares Means are actually exponentiated. Treated set (TS) -This patient set includes all randomised patients who were documented to have taken at least 1 dose of trial medication.
    End point type
    Primary
    End point timeframe
    From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days
    End point values
    		 Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects analysed
    3941 [1]
    3939 [2]
    Units: Rate per patient−year
        least squares mean (confidence interval 99%)
    0.97 (0.90 to 1.03)
    0.90 (0.84 to 0.96)
    Notes
    [1] - TS
    [2] - TS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Annualised rate of moderate to severe COPD exacerbation was analysed using a negative binomial model including the fixed, categorical effect of treatment as well as the logarithm of the treatment exposure as an offset.
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0498
    Method
    		 Negative binomial model
    Parameter type
    		 Ratio of rates vs. Tiotropium 5 μg
    Point estimate
    0.93
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.02
    Notes
    [3] - This hypothesis testing strategy ensures that the overall type I error is protected at 2-sided 0.01 level. Ratio of events Tiotropium (5 μg) + Olodaterol (5 μg) versus Tiotropium (5 μg) is provided.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Model was based on HERMES- Covariates: age, sex, smoking status, baseline Long-acting Beta-agonist/inhaled corticosteroid, region and percent predicted post-bronchodilator Forced Expiratory Volume in One Second
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.008
    Method
    		 Negative binomial model
    Parameter type
    		 Ratio of rates
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 0.98
    Notes
    [4] - Ratio of rates Tiotropium (5 μg) versus Tiotropium (5 μg) + Olodaterol (5 μg) is provided.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Model was based on TRINITY/TRILOGY- Covariates: Treatment, region, severity of airflow limitation, and smoking status as effects, and exacerbations treated with antibiotics/steroids in previous year.
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0011
    Method
    		 Negative binomial model
    Parameter type
    		 Ratio of rates
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 0.96
    Notes
    [5] - Ratio of rates Tiotropium (5 μg) versus Tiotropium (5 μg) + Olodaterol (5 μg) is provided.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Model was based on SPARK/FLAME- Covariates: Smoking status, baseline inhaled corticosteroid, Global Initiative on Chronic Obstructive Lung Disease stage, region, COPD Assessment Test score (replacing baseline symptom score), exacerbations treated with antibiotics/steroids history in previous year (replacing 1-year history of exacerbations)
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.001
    Method
    		 Negative binomial model
    Parameter type
    		 Ratio of rates
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 0.96
    Notes
    [6] - Ratio of rates Tiotropium (5 μg) versus Tiotropium (5 μg) + Olodaterol (5 μg) is provided.

    Secondary: Time to first moderate to severe COPD exacerbation during the actual treatment period.

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    End point title
    		 Time to first moderate to severe COPD exacerbation during the actual treatment period.
    End point description
    Key secondary endpoint: Time to first moderate to severe COPD exacerbation during the actual treatment period per treatment. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. The median was not estimated due to less than 50% of patients having an event. Hence the number of patients with at least one moderate to severe COPD exacerbation is presented. Treated set.
    End point type
    Secondary
    End point timeframe
    From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days
    End point values
    		 Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects analysed
    3941 [7]
    3939 [8]
    Units: Number of patients
    1777
    1746
    Notes
    [7] - TS
    [8] - TS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    A Cox’s proportional hazard model was used to estimate the hazard ratio and the corresponding Confidence Interval. A log-rank test was used to obtain the p-value
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.1188
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.03
    Notes
    [9] - This hypothesis testing strategy ensures that the overall type I error is protected at 2-sided 0.01 level. Tiotropium (5 μg) + Olodaterol (5 μg) versus Tiotropium (5 μg) 3.

    Secondary: Annualised rate of exacerbations leading to hospitalisation during the actual treatment period.

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    End point title
    		 Annualised rate of exacerbations leading to hospitalisation during the actual treatment period.
    End point description
    Annualised rate of exacerbations leading to hospitalisation during the actual treatment period was calculated per treatment per patient−year. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. Treated set.
    End point type
    Secondary
    End point timeframe
    From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days
    End point values
    		 Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects analysed
    3941 [10]
    3939 [11]
    Units: Rate per patient−year
        least squares mean (confidence interval 95%)
    0.20 (0.18 to 0.22)
    0.18 (0.16 to 0.20)
    Notes
    [10] - TS
    [11] - TS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Annualised rate of exacerbations leading to hospitalization was analysed using a negative binomial model including the fixed, categorical effect of treatment as well as the logarithm of the treatment exposure as an offset.
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 = 0.1265
    Method
    		 Negative binomial model
    Parameter type
    		 Ratio of events vs. Tiotropium 5 μg
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.03
    Notes
    [12] - Ratio of events Tiotropium (5 μg) + Olodaterol (5 μg) versus Tiotropium (5 μg) is provided.

    Secondary: Time to all-cause mortality occurring during the actual treatment period.

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    End point title
    		 Time to all-cause mortality occurring during the actual treatment period.
    End point description
    Time to all-cause mortality occurring during the actual treatment period per treatment. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. The median was not estimated due to less than 50% of patients having an event. Hence the number of patients with all-cause mortality is presented. Treated set.
    End point type
    Secondary
    End point timeframe
    From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days
    End point values
    		 Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects analysed
    3941 [13]
    3939 [14]
    Units: Number of patients
    32
    36
    Notes
    [13] - TS
    [14] - TS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    A Cox’s proportional hazard model was used to estimate the hazard ratio and the corresponding Confidence Interval. A log-rank test was used to obtain the p-value
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.7357
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.75
    Notes
    [15] - Tiotropium (5 μg) + Olodaterol (5 μg) versus Tiotropium (5 μg)

    Secondary: Time to first COPD exacerbation leading to hospitalisation during the actual treatment period.

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    End point title
    		 Time to first COPD exacerbation leading to hospitalisation during the actual treatment period.
    End point description
    Time to first COPD exacerbation leading to hospitalisation during the actual treatment period per treatment. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. The median was not estimated due to less than 50% of patients having an event. Hence the number of patients with at least one moderate to severe COPD exacerbation leading to hospitalisation is presented. Treated set.
    End point type
    Secondary
    End point timeframe
    From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days
    End point values
    		 Tiotropium 5 microgram (μg) Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects analysed
    3941 [16]
    3939 [17]
    Units: Number of patients
    469
    450
    Notes
    [16] - TS
    [17] - TS
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    A Cox’s proportional hazard model was used to estimate the hazard ratio and the corresponding Confidence Interval. A log-rank test was used to obtain the p-value
    Comparison groups
    Tiotropium 5 microgram (μg) v Tiotropium (5 μg) + Olodaterol (5 μg)
    Number of subjects included in analysis
    7880
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.2773
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.06
    Notes
    [18] - Tiotropium (5 μg) + Olodaterol (5 μg) versus Tiotropium (5 μg)

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of trial medication until 21 days after last in-take of trial medication, up to 381 days.
    Adverse event reporting additional description
    Safety analyses were based on the treated set, which included all randomised patients who took at least 1 dose of trial medication during the randomised treatment period. Patients were only actively requested to report adverse events during the on-treatment period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Tiotropium (5 μg) + Olodaterol (5 μg)
    Reporting group description
    		 Patient received 5 μg Tiotropium + 5 μg Olodaterol fixed-dose combination (FDC) inhalation solution – RESPIMAT inhaler once daily orally for 360 days.

    Reporting group title
    Tiotropium 5 microgram (μg)
    Reporting group description
    		 Patient received 5 μg Tiotropium inhalation solution – RESPIMAT inhaler once daily orally for 360 days.

    Serious adverse events
    		 Tiotropium (5 μg) + Olodaterol (5 μg) Tiotropium 5 microgram (μg)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    810 / 3939 (20.56%)
    862 / 3941 (21.87%)
         number of deaths (all causes)
    92
    98
         number of deaths resulting from adverse events
    92
    98
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basosquamous carcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Basal cell carcinoma
         subjects affected / exposed
    10 / 3939 (0.25%)
    6 / 3941 (0.15%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal neoplasm
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    2 / 3939 (0.05%)
    5 / 3941 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone neoplasm
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Breast cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Carcinoid tumour
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellopontine angle tumour
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic myeloid leukaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Colon cancer
         subjects affected / exposed
    2 / 3939 (0.05%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon neoplasm
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear neoplasm
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    6 / 3939 (0.15%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatic cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypopharyngeal cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukaemia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    2 / 3939 (0.05%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung infiltration malignant
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (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
    2 / 3939 (0.05%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Lung neoplasm malignant
         subjects affected / exposed
    13 / 3939 (0.33%)
    7 / 3941 (0.18%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Lymphocytic leukaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to adrenals
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic lymphoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm prostate
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucoepidermoid carcinoma of salivary gland
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         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
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral haemangioma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal neoplasm
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Penis carcinoma metastatic
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary renal cell carcinoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal cancer
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal cancer metastatic
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Plasma cell myeloma
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    8 / 3939 (0.20%)
    8 / 3941 (0.20%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Prostate cancer recurrent
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal adenoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Small cell lung cancer metastatic
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    5 / 3939 (0.13%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (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
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord neoplasm
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic arteriosclerosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    3 / 3939 (0.08%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic thrombosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood pressure inadequately controlled
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial disorder
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    3 / 3939 (0.08%)
    5 / 3941 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    8 / 3941 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    6 / 3939 (0.15%)
    9 / 3941 (0.23%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic arteriosclerosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    3 / 3939 (0.08%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macroangiopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microscopic polyangiitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    3 / 3939 (0.08%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery occlusion
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subgaleal haematoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboangiitis obliterans
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Enterostomy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder operation
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implantable defibrillator insertion
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung transplant
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic operation
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transurethral prostatectomy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    3 / 3939 (0.08%)
    14 / 3941 (0.36%)
         occurrences causally related to treatment / all
    0 / 3
    2 / 14
         deaths causally related to treatment / all
    0 / 3
    2 / 14
    Hyperplasia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    10 / 3939 (0.25%)
    11 / 3941 (0.28%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 3939 (0.08%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         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
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    2 / 3939 (0.05%)
    6 / 3941 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 5
    Pain
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site haematoma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site pain
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent restenosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 3939 (0.10%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Acquired hydrocele
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical polyp
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    4 / 3939 (0.10%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         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
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Alveolitis allergic
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    21 / 3939 (0.53%)
    24 / 3941 (0.61%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 25
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    Asthma
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial haemorrhage
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial obstruction
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial secretion retention
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    394 / 3939 (10.00%)
    405 / 3941 (10.28%)
         occurrences causally related to treatment / all
    5 / 506
    8 / 540
         deaths causally related to treatment / all
    0 / 11
    0 / 9
    Chronic respiratory failure
         subjects affected / exposed
    1 / 3939 (0.03%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 3939 (0.15%)
    11 / 3941 (0.28%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cough
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    3 / 3939 (0.08%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal oedema
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung consolidation
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiogenic pulmonary oedema
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    5 / 3939 (0.13%)
    8 / 3941 (0.20%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    3 / 3939 (0.08%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    9 / 3939 (0.23%)
    9 / 3941 (0.23%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Pulmonary artery thrombosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    11 / 3939 (0.28%)
    5 / 3941 (0.13%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 5
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    3 / 3939 (0.08%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    4 / 3939 (0.10%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reflux laryngitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord polyp
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status asthmaticus
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    33 / 3939 (0.84%)
    43 / 3941 (1.09%)
         occurrences causally related to treatment / all
    0 / 35
    1 / 47
         deaths causally related to treatment / all
    0 / 6
    0 / 9
    Psychiatric disorders
    Brief psychotic disorder with marked stressors
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol abuse
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Depression
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device malfunction
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device lead damage
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device breakage
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood lactic acid increased
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breath sounds absent
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PCO2 increased
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Brain contusion
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (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
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic stenosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain herniation
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns second degree
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    10 / 3939 (0.25%)
    12 / 3941 (0.30%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    3 / 3939 (0.08%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nail injury
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Occupational exposure to product
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial reocclusion
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Petroleum distillate poisoning
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative hernia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    4 / 3939 (0.10%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skull fracture
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress fracture
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Subdural haematoma
         subjects affected / exposed
    4 / 3939 (0.10%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture rupture
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral injury
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular procedure complication
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (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
    Myocardial bridging
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Porokeratosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal anomaly congenital
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermoid cyst
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syringomyelia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Accelerated idioventricular rhythm
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    1 / 3939 (0.03%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aortic valve disease mixed
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    6 / 3939 (0.15%)
    14 / 3941 (0.36%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    11 / 3939 (0.28%)
    9 / 3941 (0.23%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Angina pectoris
         subjects affected / exposed
    4 / 3939 (0.10%)
    8 / 3941 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    18 / 3939 (0.46%)
    12 / 3941 (0.30%)
         occurrences causally related to treatment / all
    1 / 20
    2 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial flutter
         subjects affected / exposed
    1 / 3939 (0.03%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    8 / 3939 (0.20%)
    8 / 3941 (0.20%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 7
    0 / 6
    Cardiac failure acute
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    23 / 3939 (0.58%)
    21 / 3941 (0.53%)
         occurrences causally related to treatment / all
    2 / 26
    0 / 23
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiac failure chronic
         subjects affected / exposed
    5 / 3939 (0.13%)
    5 / 3941 (0.13%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    3 / 3939 (0.08%)
    6 / 3941 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 6
         deaths causally related to treatment / all
    0 / 2
    1 / 4
    Cardiac failure congestive
         subjects affected / exposed
    17 / 3939 (0.43%)
    14 / 3941 (0.36%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 15
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         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 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Congestive cardiomyopathy
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    5 / 3939 (0.13%)
    5 / 3941 (0.13%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale acute
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    8 / 3939 (0.20%)
    11 / 3941 (0.28%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale chronic
         subjects affected / exposed
    0 / 3939 (0.00%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microvascular coronary artery disease
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (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
    3 / 3939 (0.08%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    10 / 3939 (0.25%)
    13 / 3941 (0.33%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 13
         deaths causally related to treatment / all
    0 / 3
    0 / 6
    Myocardial haemorrhage
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    4 / 3939 (0.10%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tachycardia
         subjects affected / exposed
    0 / 3939 (0.00%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Acoustic neuritis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amnesia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anterior interosseous syndrome
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol induced persisting dementia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Brain oedema
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral thrombosis
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    8 / 3939 (0.20%)
    7 / 3941 (0.18%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    Dementia
         subjects affected / exposed
    3 / 3939 (0.08%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic cerebral infarction
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Facial paresis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 3939 (0.00%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial neuralgia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    3 / 3939 (0.08%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemianopia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    5 / 3939 (0.13%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemianaesthesia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mononeuropathy
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monoplegia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve root compression
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelopathy
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Quadriparesis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychomotor hyperactivity
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Quadriplegia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    4 / 3939 (0.10%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    5 / 3939 (0.13%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vocal cord paralysis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         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
    Anaemia
         subjects affected / exposed
    5 / 3939 (0.13%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Acute vestibular syndrome
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deafness
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deafness neurosensory
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoacusis
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden hearing loss
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Age-related macular degeneration
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amaurosis fugax
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    3 / 3939 (0.08%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract subcapsular
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eyelid ptosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gaze palsy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open angle glaucoma
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular fibrosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular hole
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular degeneration
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vein thrombosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal tear
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 3939 (0.10%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    3 / 3939 (0.08%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 3939 (0.00%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    4 / 3939 (0.10%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 3939 (0.05%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oesophageal obstruction
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising colitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric artery thrombosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cholangitis acute
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 3939 (0.05%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 3939 (0.00%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    4 / 3939 (0.10%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin necrosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    15 / 3939 (0.38%)
    7 / 3941 (0.18%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute prerenal failure
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    3 / 3939 (0.08%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal salt-wasting syndrome
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral fistula
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    4 / 3939 (0.10%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compartment syndrome
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cartilage hypertrophy
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle tightness
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    6 / 3939 (0.15%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sarcopenia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sjogren's syndrome
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    3 / 3939 (0.08%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acinetobacter infection
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Botulism
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    4 / 3939 (0.10%)
    7 / 3941 (0.18%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic tonsillitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon gangrene
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 3939 (0.10%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Giardiasis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (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 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    4 / 3939 (0.10%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemophilus infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 3939 (0.03%)
    10 / 3941 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    15 / 3939 (0.38%)
    15 / 3941 (0.38%)
         occurrences causally related to treatment / all
    0 / 17
    2 / 15
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective glossitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal gangrene
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 3939 (0.03%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung infection
         subjects affected / exposed
    2 / 3939 (0.05%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurosyphilis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral bacterial infection
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    132 / 3939 (3.35%)
    144 / 3941 (3.65%)
         occurrences causally related to treatment / all
    0 / 145
    2 / 159
         deaths causally related to treatment / all
    0 / 3
    0 / 7
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    3 / 3939 (0.08%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoas abscess
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Scrotal abscess
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    9 / 3939 (0.23%)
    10 / 3941 (0.25%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Rotavirus infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis syndrome
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    5 / 3939 (0.13%)
    3 / 3941 (0.08%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic arthritis staphylococcal
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Strongyloidiasis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    3 / 3939 (0.08%)
    5 / 3941 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tracheobronchitis
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    3 / 3939 (0.08%)
    12 / 3941 (0.30%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 3939 (0.00%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Decreased appetite
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte depletion
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 3939 (0.05%)
    4 / 3941 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    2 / 3939 (0.05%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 3939 (0.00%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    2 / 3941 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 3939 (0.03%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 3939 (0.08%)
    1 / 3941 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 3939 (0.03%)
    0 / 3941 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Tiotropium (5 μg) + Olodaterol (5 μg) Tiotropium 5 microgram (μg)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1770 / 3939 (44.94%)
    1786 / 3941 (45.32%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    203 / 3939 (5.15%)
    232 / 3941 (5.89%)
         occurrences all number
    236
    264
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1519 / 3939 (38.56%)
    1504 / 3941 (38.16%)
         occurrences all number
    2454
    2514
    Infections and infestations
    Viral upper respiratory tract infection
         subjects affected / exposed
    281 / 3939 (7.13%)
    293 / 3941 (7.43%)
         occurrences all number
    366
    355

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jul 2015
    The global amendment introduced administrative changes, corrections, and added clarifications. An optional spirometric assessment substudy was added. This substudy was introduced to allow for better characterisation of the air flow limitation. The following exclusion criteria were revised: urinalysis was removed (exclusion criterion #2); medication restrictions and wash-out periods were updated for oral corticosteroid medication (exclusion criterion #15) and newly added for antibiotics (exclusion criterion #16). Information on permitted medications and medication restrictions as well as on restrictions on diet and life style was updated. The enrolment average per site was increased to 10 to 12 patients. The visit schedule was revised to allow the expansion of the screening period between V1 and V2 by an additional 1 week. Clarifications were introduced to the procedures for Visit 6/end of treatment, timing of procedures in case of premature discontinuation, and the Follow-up Visit.

    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.
    One site was closed for cause due to data irregularities so data of 21 patients excluded from the patient sets used for analysis. A "Missing" category is unavailable hence 1 patient with a missing age group is added to "Elderly (From 65-84 years)".
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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