Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Edoxaban Versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation – In Atrial Fibrillation. ENVISAGE-TAVI AF

    Summary
    EudraCT number
    		 2016-003930-26
    Trial protocol
    		 BE   AT   GB   DE   ES   NL   IT  
    Global end of trial date
    28 Feb 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Mar 2022
    First version publication date
    17 Mar 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    DU176B-C-U4001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02943785
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Daiichi Sankyo, Inc.
    Sponsor organisation address
    211 Mount Airy Rd, Basking Ridge, United States, 07920
    Public contact
    Clinical Director, Daiichi Sankyo Inc., +1 908 992 6400, CTRinfo@dsi.com
    Scientific contact
    Clinical Director, Daiichi Sankyo Inc., +1 908 992 6400, CTRinfo@dsi.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
    28 Feb 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Feb 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Co-Primary Objectives •To assess the effect of Edoxaban versus vitamin K antagonist (VKA) on net adverse clinical events (NACE), i.e., the composite of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SEE), valve thrombosis, and major bleeding (International Society on Thrombosis and Haemostasis [ISTH] definition). •To assess the effect of Edoxaban versus VKA on major bleeding (ISTH definition).
    Protection of trial subjects
    The study protocol, amendments (if any), the informed consent form(s), and information sheets were approved by the appropriate and applicable Independent Ethics Committees (IECs) or Institutional Review Boards (IRBs). In addition, this study was conducted in compliance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki, the International Council for Harmonisation (ICH) consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and applicable regulatory requirement(s)
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 55
    Country: Number of subjects enrolled
    Poland: 20
    Country: Number of subjects enrolled
    Spain: 344
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    Austria: 62
    Country: Number of subjects enrolled
    Belgium: 34
    Country: Number of subjects enrolled
    France: 46
    Country: Number of subjects enrolled
    Germany: 336
    Country: Number of subjects enrolled
    Italy: 132
    Country: Number of subjects enrolled
    Japan: 159
    Country: Number of subjects enrolled
    Canada: 14
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Switzerland: 34
    Country: Number of subjects enrolled
    United States: 154
    Worldwide total number of subjects
    1426
    EEA total number of subjects
    1029
    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)
    10
    From 65 to 84 years
    948
    85 years and over
    468

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 1426 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment at 173 clinic sites in Europe, Asia, and North America.

    Pre-assignment
    Screening details
    		 Participants in the study underwent successful transcatheter aortic valve implantation (TAVI) and had a preexisting atrial fibrillation (AF) or new onset AF.

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Open-label

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Edoxaban
    Arm description
    		 Patients randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Edoxaban
    Investigational medicinal product code
    Other name
    Savaysa, Lixiana
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    15 mg, 30 mg and 60 mg film coated tablet for oral use (with anti-platelet therapy pre-declared at randomization if prescribed)

    Arm title
    		 Vitamin K Antagonist (VKA)
    Arm description
    		 Patients randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Vitamin K Antagonist (VKA)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dosed at International Normalized Ratio (INR) levels, which is a test of how long it takes for blood to clot. Standard of Care treatment in the country location (with anti-platelet therapy pre-declared at randomization if prescribed).

    Number of subjects in period 1
    		Edoxaban Vitamin K Antagonist (VKA)
    Started
    713
    713
    Completed
    431
    350
    Not completed
    282
    363
         Consent withdrawn by subject
    63
    126
         Physician decision
    23
    47
         Did not receive any study medication
    21
    28
         Adverse event, non-fatal
    112
    97
         Death
    46
    46
         Not specified
    16
    19
         Lost to follow-up
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Edoxaban
    Reporting group description
    		 Patients randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.

    Reporting group title
    Vitamin K Antagonist (VKA)
    Reporting group description
    		 Patients randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.

    Reporting group values
    		 Edoxaban Vitamin K Antagonist (VKA) Total
    Number of subjects
    		 713 713 1426
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 5 5 10
        From 65-84 years
    		 473 475 948
        85 years and over
    		 235 233 468
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 82.1 ( 5.4 ) 82.1 ( 5.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 347 331 678
        Male
    		 366 382 748
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 92 89 181
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 4 5
        White
    		 593 594 1187
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 27 26 53
    Hypertension
    Units: Subjects
        Yes
    		 647 657 1304
        No
    		 66 56 122
    Diabetes mellitus
    Units: Subjects
        Yes
    		 270 257 527
        No
    		 443 456 899
    Congestive heart failure
    Units: Subjects
        Yes
    		 591 619 1210
        No
    		 122 94 216
    Mitral valve disease
    Units: Subjects
        Yes
    		 57 60 117
        No
    		 656 653 1309
    History of stroke or transient ischemic attack
    Units: Subjects
        Yes
    		 123 116 239
        No
    		 590 597 1187
    Coronary artery disease
    Units: Subjects
        Yes
    		 293 297 590
        No
    		 420 416 836
    Congestive heart failure, NYHA Class III or IV status
    Units: Subjects
        Yes
    		 314 328 642
        No
    		 399 385 784
    Prior coronary bypass surgery
    Units: Subjects
        Yes
    		 67 60 127
        No
    		 646 653 1299
    Prior percutaneous coronary intervention
    Units: Subjects
        Yes
    		 176 192 368
        No
    		 537 521 1058
    Prior myocardial infarction
    Units: Subjects
        Yes
    		 97 101 198
        No
    		 616 612 1228
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 74.6 ( 17.9 ) 76.0 ( 17.3 ) -
    Body mass index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 27.5 ( 5.7 ) 27.9 ( 5.4 ) -
    Creatinine clearance (Cockcroft-Gault formula)
    Units: mL/min
        arithmetic mean (standard deviation)
    		 57.9 ( 24.0 ) 58.6 ( 24.3 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Edoxaban
    Reporting group description
    		 Patients randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.

    Reporting group title
    Vitamin K Antagonist (VKA)
    Reporting group description
    		 Patients randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.

    Primary: Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on ISTH Criteria in Patients Taking Edoxaban vs VKA

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on ISTH Criteria in Patients Taking Edoxaban vs VKA
    End point description
    The composite endpoint net adverse clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding per definition of the International Society on Thrombosis and Haemostasis (ISTH].
    End point type
    Primary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with net adverse clinical events
    170
    157
    Statistical analysis title
    		 Noninferiority test of Edoxaban vs VKA
    Comparison groups
    Edoxaban v Vitamin K Antagonist (VKA)
    Number of subjects included in analysis
    1426
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0141 [1]
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.31
    Notes
    [1] - The two-sided p-value (Noninferiority) was based on the noninferiority margin of 1.38.

    Primary: Number of Patients Who Experienced Major Bleeding (Adjudicated Data) Based on ISTH Criteria in Patients Taking Edoxaban vs VKA

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Major Bleeding (Adjudicated Data) Based on ISTH Criteria in Patients Taking Edoxaban vs VKA
    End point description
    ISTH Bleeding Criteria for Major Bleeding are defined as clinically overt bleeding that is associated with: a fall in hemoglobin of 2 g/dL (1.24 mmol/L) or more, or a transfusion of 2 or more units of whole blood or packed red blood cells, or symptomatic bleeding into a critical site or organ such as intracranial, intraspinal, intraocular, retroperitoneal, pericardial, intra-articular, or intramuscular with compartment syndrome, or a fatal outcome.
    End point type
    Primary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with major bleeding
    98
    68
    Statistical analysis title
    		 Noninferiority test of Edoxaban vs VKA
    Comparison groups
    Edoxaban v Vitamin K Antagonist (VKA)
    Number of subjects included in analysis
    1426
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.9267 [2]
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 1.91
    Notes
    [2] - The two-sided p-value (Noninferiority) was based on the noninferiority margin of 1.38.

    Secondary: Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on TIMI Criteria in Patients Taking Edoxaban vs VKA

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on TIMI Criteria in Patients Taking Edoxaban vs VKA
    End point description
    The composite endpoint of net adverse event clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding based on Thrombolysis in Myocardial Infarction (TIMI) criteria. Bleeding by TIMI criteria was defined as the following: (1) Major, any intracranial hemorrhage or any clinically overt bleeding, (including bleeding evident in imaging studies) associated with a fall of hemoglobin (Hb) of ≥ 5g/dL or fatal bleeding and (2) Minor, any clinically overt bleeding associated with a fall in Hb ≥ 3g/dL but < 5 g/dL.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Composite endpoint NACE (TIMI)
    154
    141
        Composite of major and minor bleeding (TIMI)
    72
    42
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on BARC Type 3 or 5 Criteria in Patients Taking Edoxaban vs VKA

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on BARC Type 3 or 5 Criteria in Patients Taking Edoxaban vs VKA
    End point description
    The composite endpoint of net adverse event clinical events (NACE) included all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding based on Bleeding Academic Research Consortium (BARC) Type 3 or 5 criteria. Major bleeding by BARC criteria was defined as Type 3: clinical, laboratory, and/or imaging evidence of bleeding with provider responses; Type 3a: any transfusion with overt bleeding; overt bleeding plus Hb drop of 3 to < 5 g/dL; Type 3b: overt bleeding plus Hb drop ≥ 5 g/dL; cardiac tamponade; bleeding requiring surgical intervention; bleeding requiring intravenous vasoactive drugs; Type 3c: intracranial hemorrhage; subcategories confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision; Type 5: fatal bleeding; Type 5a: probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious; Type 5b: definite fatal bleeding; overt bleeding or autopsy or imaging confirmation.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Composite endpoint NACE (BARC Type 3 or 5)
    164
    151
        Major bleeding (BARC Type 3 or 5)
    89
    57
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on GUSTO Criteria in Patients Taking Edoxaban vs VKA

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on GUSTO Criteria in Patients Taking Edoxaban vs VKA
    End point description
    The composite endpoint of net adverse event clinical events (NACE) included all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding based on Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO). GUSTO criteria was defined as the following: severe or life threatening: intracerebral hemorrhage or resulting in substantial hemodynamic compromise requiring treatment and moderate: requiring blood transfusion but not resulting in hemodynamic compromise.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Composite endpoint NACE (GUSTO)
    160
    146
        Severe/life threatening, moderate bleeding (GUSTO)
    82
    51
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Major Adverse Cardiac Events (MACE) in Patients Taking Edoxaban vs VKA (Adjudicated Data)

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Major Adverse Cardiac Events (MACE) in Patients Taking Edoxaban vs VKA (Adjudicated Data)
    End point description
    Major adverse cardiac events (MACE) is defined as the composite of all-cause death (excluding adjudicated noncardiac death), MI, or repeat coronary revascularization of the target lesion.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with MACE
    61
    53
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Major Adverse Cardiac and Cerebrovascular Events (MACCE) in Patients Taking Edoxaban vs VKA (Adjudicated Data)

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Major Adverse Cardiac and Cerebrovascular Events (MACCE) in Patients Taking Edoxaban vs VKA (Adjudicated Data)
    End point description
    Major adverse cardiac and cerebrovascular events (MACCE) is defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, stroke (ischemic, hemorrhagic, or undetermined), or repeat coronary revascularization of the target lesion.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with MACCE
    86
    80
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced a Composite of Adverse Events in Patients Taking Edoxaban vs VKA

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced a Composite of Adverse Events in Patients Taking Edoxaban vs VKA
    End point description
    A composite of clinical adverse events included cardiovascular death, MI ischemic stroke, SEE, valve thrombosis, and major bleeding as defined by ISTH criteria.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with a composite of adverse events
    151
    123
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Stroke Events (Ischemic, Hemorrhagic, Undetermined) in Patients Taking Edoxaban vs VKA (Adjudicated Data)

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Stroke Events (Ischemic, Hemorrhagic, Undetermined) in Patients Taking Edoxaban vs VKA (Adjudicated Data)
    End point description
    Stroke events are categorized as any stroke, fatal stroke, and non-fatal stroke.
    End point type
    Secondary
    End point timeframe
    Baseline to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Any stroke - ischemic/hemorrhagic/undetermined
    29
    35
        Fatal stroke - ischemic/hemorrhagic/undetermined
    4
    3
        Non-fatal stroke-ischemic/hemorrhagic/undetermined
    25
    32
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Systemic Embolic Events in Patients Taking Edoxaban vs VKA (Adjudicated Data)

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Systemic Embolic Events in Patients Taking Edoxaban vs VKA (Adjudicated Data)
    End point description
    Systemic thromboembolism [non-central nervous system] is defined as abrupt vascular insufficiency of an extremity or organ associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (e.g., trauma, atherosclerosis, instrumentation).
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with systemic embolic events
    2
    3
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Myocardial Infarctions (MI) in Patients Taking Edoxaban vs VKA (Adjudicated Data)

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Myocardial Infarctions (MI) in Patients Taking Edoxaban vs VKA (Adjudicated Data)
    End point description
    Peri-procedural MI was defined as new ischemic symptoms or signs and elevated cardiac biomarkers within 72 hours after index procedure, consisting of at least one sample post-procedure with a peak value exceeding 15x as the upper reference limit (URL) for troponin or 5x for CK-MB. Spontaneous MI is defined as any one of the following: Detection of rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile URL, together with the evidence of myocardial ischemia with at least one of the following: Symptoms of ischemia; ECG changes indicative of new ischemia; New pathological Q-waves in at least two contiguous leads; Imaging evidence of a new loss of viable myocardium or new wall motion abnormality; Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied by new ST elevation or new left bundle branch block, and/or evidence of fresh thrombus; Pathological findings of an acute MI.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with myocardial infarctions
    12
    7
    No statistical analyses for this end point

    Secondary: Number of Patients Who Experienced Valve Thrombosis in Patients Taking Edoxaban vs VKA (Adjudicated Data)

    		 Close Top of page
    End point title
    		 Number of Patients Who Experienced Valve Thrombosis in Patients Taking Edoxaban vs VKA (Adjudicated Data)
    End point description
    Valve thrombosis was defined as any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to 36 months post-dose
    End point values
    		 Edoxaban Vitamin K Antagonist (VKA)
    Number of subjects analysed
    713
    713
    Units: participants
    number (not applicable)
        Patients with valve thrombosis
    0
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events were collected from the Safety Analysis Set from baseline up 4 weeks post-discontinuation of study treatment, up to 36 months post-dose.
    Adverse event reporting additional description
    Treatment-emergent adverse events are defined as events which start on or after any first dose of the assigned study medication regimen or started prior to but then worsened after any first dose of the assigned study medication regimen.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Edoxaban
    Reporting group description
    		 Patients randomized to receive the Edoxaban-based regimen which included 60 mg and 30 mg film coated tablets for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing followed the locally approved label.

    Reporting group title
    Vitamin K Antagonist (VKA)
    Reporting group description
    		 Patients randomized to receive the VKA-based regimen which included oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator monitored the patient and adjusted the VKA dose to maintain the dose within target.

    Serious adverse events
    		 Edoxaban Vitamin K Antagonist (VKA)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    388 / 693 (55.99%)
    372 / 684 (54.39%)
         number of deaths (all causes)
    83
    78
         number of deaths resulting from adverse events
    83
    78
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Anogenital warts
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic myelomonocytic leukaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung neoplasm
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to central nervous system
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myeloproliferative neoplasm
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neoplasm malignant
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neoplasm prostate
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm skin
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal adenocarcinoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Refractory cytopenia with unilineage dysplasia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric cancer
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Aortic occlusion
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic perforation
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic thrombosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blue toe syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic vascular disorder
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral artery embolism
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 693 (0.29%)
    9 / 684 (1.32%)
         occurrences causally related to treatment / all
    0 / 2
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    8 / 693 (1.15%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    3 / 693 (0.43%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    7 / 693 (1.01%)
    5 / 684 (0.73%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    Asthenia
         subjects affected / exposed
    4 / 693 (0.58%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    8 / 693 (1.15%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 3
         deaths causally related to treatment / all
    2 / 8
    0 / 3
    Fatigue
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    3 / 693 (0.43%)
    6 / 684 (0.88%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Impaired healing
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site haematoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    5 / 693 (0.72%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Non-cardiac chest pain
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pacemaker generated arrhythmia
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stent-graft endoleak
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sudden death
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic haematoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectocele
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    5 / 693 (0.72%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    5 / 693 (0.72%)
    7 / 684 (1.02%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Dyspnoea
         subjects affected / exposed
    11 / 693 (1.59%)
    8 / 684 (1.17%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dyspnoea exertional
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    7 / 693 (1.01%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    6 / 7
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Haemothorax
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal haematoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    5 / 693 (0.72%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumothorax
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    7 / 693 (1.01%)
    8 / 684 (1.17%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    4 / 693 (0.58%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug dependence
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Stress
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device leakage
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device power source issue
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Blood lactic acid increased
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronavirus test positive
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical condition normal
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart rate irregular
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammatory marker increased
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 693 (0.14%)
    5 / 684 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial necrosis marker increased
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight increased
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    0 / 693 (0.00%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bone contusion
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon injury
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Face injury
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    9 / 693 (1.30%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 11
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    4 / 693 (0.58%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    5 / 693 (0.72%)
    6 / 684 (0.88%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body in gastrointestinal tract
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    3 / 693 (0.43%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Heat illness
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    2 / 693 (0.29%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    2 / 693 (0.29%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open globe injury
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 693 (0.00%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.29%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Post procedural fever
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    3 / 693 (0.43%)
    5 / 684 (0.73%)
         occurrences causally related to treatment / all
    1 / 4
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Tendon rupture
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular access site haematoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site pseudoaneurysm
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    6 / 693 (0.87%)
    8 / 684 (1.17%)
         occurrences causally related to treatment / all
    4 / 8
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 693 (0.29%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    17 / 693 (2.45%)
    18 / 684 (2.63%)
         occurrences causally related to treatment / all
    0 / 17
    1 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    6 / 693 (0.87%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    3 / 693 (0.43%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    9 / 693 (1.30%)
    6 / 684 (0.88%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bifascicular block
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    6 / 693 (0.87%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 693 (0.29%)
    7 / 684 (1.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 6
    Cardiac asthma
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    57 / 693 (8.23%)
    64 / 684 (9.36%)
         occurrences causally related to treatment / all
    1 / 76
    1 / 81
         deaths causally related to treatment / all
    0 / 10
    0 / 5
    Cardiac failure acute
         subjects affected / exposed
    8 / 693 (1.15%)
    11 / 684 (1.61%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiac failure chronic
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Cardiac failure congestive
         subjects affected / exposed
    23 / 693 (3.32%)
    12 / 684 (1.75%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 13
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Cardiac tamponade
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiorenal syndrome
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic left ventricular failure
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conduction disorder
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    6 / 693 (0.87%)
    8 / 684 (1.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Pericardial effusion
         subjects affected / exposed
    4 / 693 (0.58%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prosthetic cardiac valve thrombosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    2 / 693 (0.29%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular dysfunction
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Metastases to pelvis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Altered state of consciousness
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    5 / 693 (0.72%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    3 / 5
    1 / 1
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 693 (0.29%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cerebral ischaemia
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral microangiopathy
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chorea
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Choreoathetosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    3 / 693 (0.43%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cubital tunnel syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    6 / 693 (0.87%)
    5 / 684 (0.73%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysaesthesia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic cerebral infarction
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    4 / 693 (0.58%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 693 (0.14%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    2 / 3
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 693 (0.14%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    Headache
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraventricular haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    9 / 693 (1.30%)
    10 / 684 (1.46%)
         occurrences causally related to treatment / all
    6 / 11
    6 / 12
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Lacunar infarction
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Syncope
         subjects affected / exposed
    13 / 693 (1.88%)
    12 / 684 (1.75%)
         occurrences causally related to treatment / all
    0 / 14
    1 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    7 / 693 (1.01%)
    8 / 684 (1.17%)
         occurrences causally related to treatment / all
    2 / 7
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 693 (0.00%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    31 / 693 (4.47%)
    11 / 684 (1.61%)
         occurrences causally related to treatment / all
    17 / 36
    6 / 12
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Anaemia folate deficiency
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    5 / 693 (0.72%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heparin-induced thrombocytopenia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypochromic anaemia
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    3 / 693 (0.43%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrogenic anaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normochromic anaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Splenic infarction
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spontaneous haematoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 693 (0.00%)
    6 / 684 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ear and labyrinth disorders
    Tympanic membrane perforation
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular paroxysmia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Amaurosis fugax
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Choroidal detachment
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous detachment
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    7 / 693 (1.01%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocele
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenal ulcer
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 693 (0.72%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    5 / 5
    3 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Inguinal hernia
         subjects affected / exposed
    2 / 693 (0.29%)
    6 / 684 (0.88%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Intestinal obstruction
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    16 / 693 (2.31%)
    7 / 684 (1.02%)
         occurrences causally related to treatment / all
    13 / 17
    6 / 7
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Mallory-Weiss syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic failure
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Rectal haemorrhage
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Subileus
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative duodenitis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    8 / 693 (1.15%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    7 / 8
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Vomiting
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermal cyst
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 693 (0.14%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin ulcer haemorrhage
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    18 / 693 (2.60%)
    17 / 684 (2.49%)
         occurrences causally related to treatment / all
    0 / 19
    1 / 19
         deaths causally related to treatment / all
    0 / 3
    1 / 3
    Calculus bladder
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 693 (0.14%)
    5 / 684 (0.73%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    End stage renal disease
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haematuria
         subjects affected / exposed
    11 / 693 (1.59%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    5 / 12
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    4 / 693 (0.58%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal haematoma
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral haemorrhage
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    4 / 693 (0.58%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest wall haematoma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 693 (0.00%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma muscle
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    5 / 693 (0.72%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 693 (0.00%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue disorder
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    Abscess soft tissue
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acinetobacter bacteraemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alveolar osteitis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 693 (0.00%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspergilloma
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    2 / 693 (0.29%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bacterial sepsis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    4 / 693 (0.58%)
    5 / 684 (0.73%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 693 (0.29%)
    6 / 684 (0.88%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 693 (0.14%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cellulitis
         subjects affected / exposed
    3 / 693 (0.43%)
    4 / 684 (0.58%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Citrobacter sepsis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis klebsiella
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (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
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    14 / 693 (2.02%)
    7 / 684 (1.02%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Endocarditis enterococcal
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis staphylococcal
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal infection
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    2 / 693 (0.29%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Epididymitis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal tracheitis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric infection
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 693 (0.43%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin infection
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    2 / 693 (0.29%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster oticus
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected lymphocele
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective aneurysm
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Influenza
         subjects affected / exposed
    4 / 693 (0.58%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 693 (0.43%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Medical device site infection
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mycotic corneal ulcer
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumococcal bacteraemia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    39 / 693 (5.63%)
    37 / 684 (5.41%)
         occurrences causally related to treatment / all
    0 / 43
    0 / 41
         deaths causally related to treatment / all
    0 / 6
    0 / 5
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    7 / 693 (1.01%)
    13 / 684 (1.90%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salmonellosis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    6 / 693 (0.87%)
    7 / 684 (1.02%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Septic shock
         subjects affected / exposed
    5 / 693 (0.72%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Sinusitis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Streptococcal endocarditis
         subjects affected / exposed
    3 / 693 (0.43%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    21 / 693 (3.03%)
    17 / 684 (2.49%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 22
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    6 / 693 (0.87%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Viral infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cachexia
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Decreased appetite
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    3 / 693 (0.43%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    2 / 693 (0.29%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fluid retention
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fructose intolerance
         subjects affected / exposed
    1 / 693 (0.14%)
    0 / 684 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 693 (0.00%)
    1 / 684 (0.15%)
         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 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 693 (0.14%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 693 (0.14%)
    3 / 684 (0.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 693 (0.00%)
    2 / 684 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 693 (0.14%)
    1 / 684 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Edoxaban Vitamin K Antagonist (VKA)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    522 / 693 (75.32%)
    429 / 684 (62.72%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    35 / 693 (5.05%)
    23 / 684 (3.36%)
         occurrences all number
    35
    23
    Vascular disorders
    Haematoma
         subjects affected / exposed
    26 / 693 (3.75%)
    41 / 684 (5.99%)
         occurrences all number
    26
    41
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    23 / 693 (3.32%)
    36 / 684 (5.26%)
         occurrences all number
    23
    36
    Cardiac failure
         subjects affected / exposed
    78 / 693 (11.26%)
    85 / 684 (12.43%)
         occurrences all number
    78
    85
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    47 / 693 (6.78%)
    33 / 684 (4.82%)
         occurrences all number
    47
    33
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    62 / 693 (8.95%)
    40 / 684 (5.85%)
         occurrences all number
    62
    40
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    39 / 693 (5.63%)
    35 / 684 (5.12%)
         occurrences all number
    39
    35
    Epistaxis
         subjects affected / exposed
    64 / 693 (9.24%)
    30 / 684 (4.39%)
         occurrences all number
    64
    30
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    40 / 693 (5.77%)
    18 / 684 (2.63%)
         occurrences all number
    40
    18
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    45 / 693 (6.49%)
    43 / 684 (6.29%)
         occurrences all number
    45
    43
    Urinary tract infection
         subjects affected / exposed
    63 / 693 (9.09%)
    45 / 684 (6.58%)
         occurrences all number
    63
    45

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Jun 2017
    Editorial changes were incorporated to improve clarity and consistency; Japan was added as a potential participating country; and additional criteria were included to cover the potential transfer of patients during the study
    05 Jul 2018
    Minor editorial changes were incorporated to improve clarity and to reflect the changing medical practice
    29 Jul 2019
    Minor editorial changes were incorporated to improve clarity throughout the protocol, including safety/AE definitions
    17 Apr 2020
    Incorporated temporary measures while COVID-19 restrictions were in effect

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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

    European Medicines Agency © 1995-Mon May 05 17:29:27 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA