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    Clinical Trial Results:
    A randomized, active-comparator-controlled, multicenter study to assess the safety and efficacy of different doses of BAY1213790 for the prevention of venous thromboembolism in patients undergoing elective primary total knee arthroplasty, open-label to treatment and observer-blinded to BAY1213790 doses.

    Summary
    EudraCT number
    		 2016-002681-31
    Trial protocol
    		 ES   LT   CZ   DE   LV   BG   PL   GR   PT  
    Global end of trial date
    02 Jan 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Jan 2020
    First version publication date
    05 Jan 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BAY1213790/17664
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03276143
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser Wilhelm Allee, Leverkusen, Germany, 51368
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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
    02 Jan 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jan 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the safety and efficacy of different doses of BAY1213790 in comparison with those of enoxaparin in patients undergoing elective, primary, unilateral total knee arthroplasty (TKA).
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 None
    Evidence for comparator
    		 Yes
    Actual start date of recruitment
    21 Sep 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
    Canada: 1
    Country: Number of subjects enrolled
    Czech Republic: 33
    Country: Number of subjects enrolled
    Greece: 87
    Country: Number of subjects enrolled
    Israel: 80
    Country: Number of subjects enrolled
    Latvia: 99
    Country: Number of subjects enrolled
    Lithuania: 124
    Country: Number of subjects enrolled
    Poland: 133
    Country: Number of subjects enrolled
    Bulgaria: 9
    Country: Number of subjects enrolled
    Portugal: 12
    Country: Number of subjects enrolled
    Russian Federation: 49
    Country: Number of subjects enrolled
    South Africa: 41
    Country: Number of subjects enrolled
    Spain: 55
    Country: Number of subjects enrolled
    Ukraine: 90
    Worldwide total number of subjects
    813
    EEA total number of subjects
    552
    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)
    317
    From 65 to 84 years
    489
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 The first visit of the first subject was on 21-Sep-2017, the last visit of the last subject was on 02-Jan-2019.

    Pre-assignment
    Screening details
    		 945 subjects were screened of whom 132 patients were screening failures. 813 patients were enrolled and randomized, of whom 790 received a drug (either BAY1213790 or comparators). 780 patients completed the treatment phase, 752 patients completed the post-treatment observation phase.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Enoxaparin (ENO)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Enoxaparin sodium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dose of 40 mg once daily from Day 1 to Day 15

    Arm title
    		 Apixaban (API)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Apixaban
    Investigational medicinal product code
    Other name
    Eliquis
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dose of 2.5g mg twice daily from Day 2 to Day 15

    Arm title
    		 BAY1213790 0.3mg/kg (post-surgery)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Monoclonal antibody targeting FXIa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single dose of 0.3 mg per kg body weight on Day 2 (post-surgery)

    Arm title
    		 BAY1213790 0.6mg/kg (post-surgery)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Monoclonal antibody targeting FXIa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single dose of 0.6 mg per kg body weight on Day 2 (post-surgery)

    Arm title
    		 BAY1213790 1.2mg/kg (post-surgery)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Monoclonal antibody targeting FXIa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single dose of 1.2 mg per kg body weight on Day 2 (post-surgery)

    Arm title
    		 BAY1213790 1.8mg/kg (post-surgery)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Monoclonal antibody targeting FXIa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single dose of 1.8 mg per kg body weight on Day 2 (post-surgery)

    Arm title
    		 BAY1213790 0.3mg/kg (pre-surgery)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Monoclonal antibody targeting FXIa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single dose of 0.3 mg per kg body weight on Day 1 (pre-surgery)

    Arm title
    		 BAY1213790 1.8mg/kg (pre-surgery)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Monoclonal antibody targeting FXIa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single dose of 1.8 mg per kg body weight on Day 1 (pre-surgery)

    Number of subjects in period 1
    		Enoxaparin (ENO) Apixaban (API) BAY1213790 0.3mg/kg (post-surgery) BAY1213790 0.6mg/kg (post-surgery) BAY1213790 1.2mg/kg (post-surgery) BAY1213790 1.8mg/kg (post-surgery) BAY1213790 0.3mg/kg (pre-surgery) BAY1213790 1.8mg/kg (pre-surgery)
    Started
    105
    105
    107
    65
    108
    106
    109
    108
    Treatment started
    103
    100
    101
    65
    105
    101
    107
    108
    Completed
    103
    99
    99
    65
    103
    101
    105
    105
    Not completed
    2
    6
    8
    0
    5
    5
    4
    3
         Consent withdrawn by subject
    1
    3
    2
    -
    3
    2
    2
    3
         Physician decision
    -
    1
    -
    -
    -
    -
    1
    -
         Adverse event, non-fatal
    1
    1
    3
    -
    2
    1
    -
    -
         Other reasons
    -
    1
    3
    -
    -
    -
    1
    -
         Protocol deviation
    -
    -
    -
    -
    -
    2
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Enoxaparin (ENO)
    Reporting group description
    		 -

    Reporting group title
    Apixaban (API)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 0.3mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 0.6mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 1.2mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 1.8mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 0.3mg/kg (pre-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 1.8mg/kg (pre-surgery)
    Reporting group description
    		 -

    Reporting group values
    		 Enoxaparin (ENO) Apixaban (API) BAY1213790 0.3mg/kg (post-surgery) BAY1213790 0.6mg/kg (post-surgery) BAY1213790 1.2mg/kg (post-surgery) BAY1213790 1.8mg/kg (post-surgery) BAY1213790 0.3mg/kg (pre-surgery) BAY1213790 1.8mg/kg (pre-surgery) Total
    Number of subjects
    		 105 105 107 65 108 106 109 108 813
    Age Categorical
    All enrolled subjects
    Units: Subjects
        Age < 60 years
    		 22 22 27 15 24 17 21 15 163
        Age >= 60 years
    		 83 83 80 50 84 89 88 93 650
    Age Continuous
    All enrolled subjects
    Units: years
        arithmetic mean (standard deviation)
    		 66.4 ( 8.6 ) 65.9 ( 8.2 ) 65.9 ( 8.5 ) 66.4 ( 9.2 ) 66.4 ( 8.3 ) 67.6 ( 7.6 ) 66.1 ( 8.2 ) 67.7 ( 7.3 ) -
    Gender Categorical
    All enrolled subjects
    Units: Subjects
        Male
    		 29 22 32 20 21 33 25 28 210
        Female
    		 76 83 75 45 87 73 84 80 603
    Main indication for total knee arthroplasty (TKA)
    All enrolled subjects
    Units: Subjects
        Osteoarthritis
    		 97 95 101 63 104 97 102 101 760
        Rheumatoid arthritis
    		 3 2 1 1 1 1 0 1 10
        Fracture sequelae
    		 1 1 0 1 0 3 0 0 6
        Osteonecrosis
    		 1 0 0 0 0 1 0 0 2
        Other
    		 1 3 0 0 0 0 4 5 13
        TKA not performed
    		 2 4 5 0 3 4 3 1 22
    Body mass index
    All enrolled subjects
    Units: kg m-2
        arithmetic mean (standard deviation)
    		 32.72 ( 5.73 ) 32.74 ( 5.67 ) 32.20 ( 5.19 ) 31.72 ( 5.45 ) 33.89 ( 5.75 ) 31.94 ( 5.31 ) 32.26 ( 6.23 ) 33.62 ( 5.92 ) -
    Subject analysis sets

    Subject analysis set title
    Safety set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All patients who received at least one dose of study drug and had total knee arthroplasty (TKA) surgery

    Subject analysis set title
    Per Protocol Set (PPS)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All patients who received at least one dose of study drug, had a valid venography or an objectively confirmed symptomatic venous thromboembolism before Day 15 and did not have an important deviation from protocol or validity finding

    Subject analysis sets values
    		 Safety set (SAF) Per Protocol Set (PPS)
    Number of subjects
    787
    600
    Age Categorical
    All enrolled subjects
    Units: Subjects
        Age < 60 years
    153
    122
        Age >= 60 years
    634
    478
    Age Continuous
    All enrolled subjects
    Units: years
        arithmetic mean (standard deviation)
    66.6 ( 8.2 )
    66.5 ( 8.2 )
    Gender Categorical
    All enrolled subjects
    Units: Subjects
        Male
    204
    164
        Female
    583
    436
    Main indication for total knee arthroplasty (TKA)
    All enrolled subjects
    Units: Subjects
        Osteoarthritis
    756
    583
        Rheumatoid arthritis
    10
    7
        Fracture sequelae
    6
    4
        Osteonecrosis
    2
    2
        Other
    13
    4
        TKA not performed
    0
    0
    Body mass index
    All enrolled subjects
    Units: kg m-2
        arithmetic mean (standard deviation)
    32.64 ( 5.68 )
    32.48 ( 5.68 )

    End points

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    End points reporting groups
    Reporting group title
    Enoxaparin (ENO)
    Reporting group description
    		 -

    Reporting group title
    Apixaban (API)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 0.3mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 0.6mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 1.2mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 1.8mg/kg (post-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 0.3mg/kg (pre-surgery)
    Reporting group description
    		 -

    Reporting group title
    BAY1213790 1.8mg/kg (pre-surgery)
    Reporting group description
    		 -

    Subject analysis set title
    Safety set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All patients who received at least one dose of study drug and had total knee arthroplasty (TKA) surgery

    Subject analysis set title
    Per Protocol Set (PPS)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All patients who received at least one dose of study drug, had a valid venography or an objectively confirmed symptomatic venous thromboembolism before Day 15 and did not have an important deviation from protocol or validity finding

    Primary: Incidence of the composite efficacy endpoint

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    End point title
    		 Incidence of the composite efficacy endpoint
    End point description
    Incidence of the composite endpoint consisting of asymptomatic deep vein thrombosis (DVT) detected by mandatory bilateral venography, objectively confirmed symptomatic DVT, non-fatal pulmonary embolism (PE), fatal PE and unexplained death for which PE cannot be excluded from randomization up to Day 15
    End point type
    Primary
    End point timeframe
    Up to 15 days
    End point values
    		 Enoxaparin (ENO) Apixaban (API) BAY1213790 0.3mg/kg (post-surgery) BAY1213790 0.6mg/kg (post-surgery) BAY1213790 1.2mg/kg (post-surgery) BAY1213790 1.8mg/kg (post-surgery) BAY1213790 0.3mg/kg (pre-surgery) BAY1213790 1.8mg/kg (pre-surgery) Per Protocol Set (PPS)
    Number of subjects analysed
    76
    83
    76
    51
    79
    78
    77
    80
    117
    Units: Number of subjects
        Primary efficacy endpoint
    20
    12
    18
    8
    13
    14
    23
    9
    117
        - Asymptomatic deep vein thrombosis (DVT)
    20
    11
    18
    7
    13
    14
    22
    9
    114
        - Symptomatic deep vein thrombosis (DVT)
    1
    1
    1
    1
    1
    2
    1
    0
    8
        - Non-fatal pulmonary embolism (PE)
    0
    0
    0
    0
    0
    0
    0
    0
    0
        - Fatal pulmonary embolism (PE)
    0
    0
    0
    0
    0
    0
    0
    0
    0
        -Unexplained death for which PE cannot be excluded
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Statistical analysis title
    		 Difference between BAY1213790 to enoxaparin_1
    Statistical analysis description
    Difference in proportion of patients with the primary efficacy endpoint between 0.3 mg BAY1213790 post-surgery group and enoxaparin
    Comparison groups
    Enoxaparin (ENO) v BAY1213790 0.3mg/kg (post-surgery) v Per Protocol Set (PPS)
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.1385
    Method
    		 Asymptotic Wald test
    Parameter type
    		 Point estimate (%)
    Point estimate
    2.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -8.9
         upper limit
    		 14.2
    Statistical analysis title
    		 Difference between BAY1213790 to enoxaparin_2
    Statistical analysis description
    Difference in proportion of patients with the primary efficacy endpoint between 0.6 mg BAY1213790 post-surgery group and enoxaparin
    Comparison groups
    Enoxaparin (ENO) v BAY1213790 0.6mg/kg (post-surgery) v Per Protocol Set (PPS)
    Number of subjects included in analysis
    244
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0147
    Method
    		 Asymptotic Wald test
    Parameter type
    		 Point estimate (%)
    Point estimate
    10.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 22.4
    Statistical analysis title
    		 Difference between BAY1213790 to enoxaparin_3
    Statistical analysis description
    Difference in proportion of patients with the primary efficacy endpoint between 1.2 mg BAY1213790 post-surgery group and enoxaparin
    Comparison groups
    Enoxaparin (ENO) v BAY1213790 1.2mg/kg (post-surgery) v Per Protocol Set (PPS)
    Number of subjects included in analysis
    272
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0117
    Method
    		 Asymptotic Wald test
    Parameter type
    		 Point estimate (%)
    Point estimate
    9.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 20.6
    Statistical analysis title
    		 Difference between BAY1213790 to enoxaparin_4
    Statistical analysis description
    Difference in proportion of patients with the primary efficacy endpoint between 1.8 mg BAY1213790 post-surgery group and enoxaparin
    Comparison groups
    Enoxaparin (ENO) v BAY1213790 1.8mg/kg (post-surgery) v Per Protocol Set (PPS)
    Number of subjects included in analysis
    271
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0224
    Method
    		 Asymptotic Wald test
    Parameter type
    		 Point estimate (%)
    Point estimate
    8.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 19.3
    Statistical analysis title
    		 Difference between BAY1213790 to enoxaparin_5
    Statistical analysis description
    Difference in proportion of patients with the primary efficacy endpoint between 0.3 mg BAY1213790 pre-surgery group and enoxaparin
    Comparison groups
    Enoxaparin (ENO) v BAY1213790 0.3mg/kg (pre-surgery) v Per Protocol Set (PPS)
    Number of subjects included in analysis
    270
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.4211
    Method
    		 Asymptotic Wald test
    Parameter type
    		 Point estimate (%)
    Point estimate
    -3.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -15.5
         upper limit
    		 8.4
    Statistical analysis title
    		 Difference between BAY1213790 to enoxaparin_6
    Statistical analysis description
    Difference in proportion of patients with the primary efficacy endpoint between 1.8 mg BAY1213790 pre-surgery group and enoxaparin
    Comparison groups
    Enoxaparin (ENO) v BAY1213790 1.8mg/kg (pre-surgery) v Per Protocol Set (PPS)
    Number of subjects included in analysis
    273
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0073
    Method
    		 Asymptotic Wald test
    Parameter type
    		 Point estimate (%)
    Point estimate
    15.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 4.9
         upper limit
    		 25.2

    Primary: Incidence of the composite safety endpoint

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    End point title
    		 Incidence of the composite safety endpoint [1]
    End point description
    Incidence of the composite of major and clinically relevant non-major bleeding events from randomization to Day 15
    End point type
    Primary
    End point timeframe
    Up to 15 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The comparison between the BAY1213790 arms and apixaban for primary efficacy as well as all safety analyses were pre-planned to be performed descriptively.
    End point values
    		 Enoxaparin (ENO) Apixaban (API) BAY1213790 0.3mg/kg (post-surgery) BAY1213790 0.6mg/kg (post-surgery) BAY1213790 1.2mg/kg (post-surgery) BAY1213790 1.8mg/kg (post-surgery) BAY1213790 0.3mg/kg (pre-surgery) BAY1213790 1.8mg/kg (pre-surgery) Safety set (SAF)
    Number of subjects analysed
    102
    100
    102
    65
    104
    101
    106
    107
    787
    Units: Number of subjects
        Primary efficacy endpoint
    6
    2
    2
    0
    1
    3
    2
    5
    21
        Major bleeding
    0
    0
    0
    0
    0
    0
    0
    1
    1
        Clinically relevant non-major bleeding
    6
    2
    2
    0
    1
    3
    2
    4
    20
    No statistical analyses for this end point

    Secondary: Incidence of the composite secondary efficacy endpoint

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    End point title
    		 Incidence of the composite secondary efficacy endpoint
    End point description
    Incidence of the composite endpoint of symptomatic deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), fatal PE and unexplained death for which PE cannot be excluded from randomization up to Day 157 or objectively confirmed asymptomatic DVT from randomization up to Day 15
    End point type
    Secondary
    End point timeframe
    Up to 157 days
    End point values
    		 Enoxaparin (ENO) Apixaban (API) BAY1213790 0.3mg/kg (post-surgery) BAY1213790 0.6mg/kg (post-surgery) BAY1213790 1.2mg/kg (post-surgery) BAY1213790 1.8mg/kg (post-surgery) BAY1213790 0.3mg/kg (pre-surgery) BAY1213790 1.8mg/kg (pre-surgery) Per Protocol Set (PPS)
    Number of subjects analysed
    76
    83
    76
    51
    79
    78
    77
    80
    600
    Units: Number of subjects
        Secondary efficacy endpoint
    20
    13
    18
    8
    13
    14
    24
    9
    119
        -Asymptomatic deep vein thrombosis (DVT) to Day 15
    20
    11
    18
    7
    13
    14
    22
    9
    114
        -Symptomatic deep vein thrombosis (DVT)
    1
    1
    1
    1
    1
    2
    2
    0
    9
        -Non-fatal pulmonary embolism (PE)
    0
    1
    0
    0
    1
    0
    0
    1
    3
        -Fatal pulmonary embolism (PE)
    0
    0
    0
    0
    0
    0
    0
    0
    0
        -Unexplained death for which PE cannot be excluded
    0
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Incidence of the composite secondary safety endpoint

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    End point title
    		 Incidence of the composite secondary safety endpoint
    End point description
    Incidence of composite of major and clinically relevant non-major bleeding from randomization to Day 157
    End point type
    Secondary
    End point timeframe
    Up to 157 days
    End point values
    		 Enoxaparin (ENO) Apixaban (API) BAY1213790 0.3mg/kg (post-surgery) BAY1213790 0.6mg/kg (post-surgery) BAY1213790 1.2mg/kg (post-surgery) BAY1213790 1.8mg/kg (post-surgery) BAY1213790 0.3mg/kg (pre-surgery) BAY1213790 1.8mg/kg (pre-surgery) Safety set (SAF)
    Number of subjects analysed
    102
    100
    102
    65
    104
    101
    106
    107
    787
    Units: Number of subjects
        At least one secondary safety event
    7
    2
    3
    0
    1
    3
    2
    6
    24
        - Major bleeding
    0
    0
    0
    0
    0
    0
    0
    2
    2
        - Clinically relevant non-Major bleeding
    7
    2
    3
    0
    1
    3
    2
    4
    22
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first drug application up to Day 157
    Adverse event reporting additional description
    3 of 790 treated patients were excluded from SAF, because TKA was not performed.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Enoxaparin 40 mg OD
    Reporting group description
    		 Patients with TKA who received Enoxaparin sodium once daily starting either before or after TKA until venography

    Reporting group title
    Apixaban 2.5 mg BID
    Reporting group description
    		 Patients with TKA who received apixaban twice daily starting after TKA until venography

    Reporting group title
    0.3 mg/kg BAY1213790 post-surgery
    Reporting group description
    		 Patients with TKA who received 0.3 mg BAY1213790 once the day after TKA

    Reporting group title
    0.6 mg/kg BAY1213790 post-surgery
    Reporting group description
    		 Patients with TKA who received 0.6 mg BAY1213790 once the day after TKA

    Reporting group title
    1.8 mg/kg BAY1213790 post-surgery
    Reporting group description
    		 Patients with TKA who received 1.8 mg BAY1213790 once the day after TKA

    Reporting group title
    1.2 mg/kg BAY1213790 post-surgery
    Reporting group description
    		 Patients with TKA who received 1.2 mg BAY1213790 once the day after TKA

    Reporting group title
    0.3 mg/kg BAY1213790 pre-surgery
    Reporting group description
    		 Patients with TKA who received 0.3 mg BAY1213790 once the day before TKA

    Reporting group title
    1.8 mg/kg BAY1213790 pre-surgery
    Reporting group description
    		 Patients with TKA who received 1.8 mg BAY1213790 once the day before TKA

    Serious adverse events
    		 Enoxaparin 40 mg OD Apixaban 2.5 mg BID 0.3 mg/kg BAY1213790 post-surgery 0.6 mg/kg BAY1213790 post-surgery 1.8 mg/kg BAY1213790 post-surgery 1.2 mg/kg BAY1213790 post-surgery 0.3 mg/kg BAY1213790 pre-surgery 1.8 mg/kg BAY1213790 pre-surgery
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 102 (10.78%)
    5 / 100 (5.00%)
    9 / 102 (8.82%)
    4 / 65 (6.15%)
    7 / 101 (6.93%)
    10 / 104 (9.62%)
    5 / 106 (4.72%)
    9 / 107 (8.41%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hyperaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    1 / 65 (1.54%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    1 / 102 (0.98%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    1 / 65 (1.54%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    2 / 106 (1.89%)
    2 / 107 (1.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Knee arthroplasty
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Physiotherapy
         subjects affected / exposed
    2 / 102 (1.96%)
    0 / 100 (0.00%)
    2 / 102 (1.96%)
    1 / 65 (1.54%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rehabilitation therapy
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    1 / 106 (0.94%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Radius fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    1 / 102 (0.98%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural fistula
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incision site inflammation
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural swelling
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    2 / 102 (1.96%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral ischaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    1 / 106 (0.94%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    1 / 102 (0.98%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pemphigus
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    1 / 102 (0.98%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint contracture
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    2 / 102 (1.96%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    1 / 106 (0.94%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    1 / 107 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint stiffness
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    1 / 102 (0.98%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    2 / 101 (1.98%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    1 / 65 (1.54%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    1 / 104 (0.96%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    1 / 65 (1.54%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    1 / 102 (0.98%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    0 / 104 (0.00%)
    0 / 106 (0.00%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device site joint infection
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 100 (0.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    2 / 104 (1.92%)
    1 / 106 (0.94%)
    0 / 107 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Enoxaparin 40 mg OD Apixaban 2.5 mg BID 0.3 mg/kg BAY1213790 post-surgery 0.6 mg/kg BAY1213790 post-surgery 1.8 mg/kg BAY1213790 post-surgery 1.2 mg/kg BAY1213790 post-surgery 0.3 mg/kg BAY1213790 pre-surgery 1.8 mg/kg BAY1213790 pre-surgery
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    51 / 102 (50.00%)
    25 / 100 (25.00%)
    42 / 102 (41.18%)
    25 / 65 (38.46%)
    31 / 101 (30.69%)
    38 / 104 (36.54%)
    60 / 106 (56.60%)
    74 / 107 (69.16%)
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    6 / 102 (5.88%)
    0 / 100 (0.00%)
    2 / 102 (1.96%)
    2 / 65 (3.08%)
    1 / 101 (0.99%)
    4 / 104 (3.85%)
    2 / 106 (1.89%)
    1 / 107 (0.93%)
         occurrences all number
    6
    0
    2
    2
    1
    4
    2
    1
    Haemoglobin decreased
         subjects affected / exposed
    18 / 102 (17.65%)
    4 / 100 (4.00%)
    3 / 102 (2.94%)
    1 / 65 (1.54%)
    6 / 101 (5.94%)
    8 / 104 (7.69%)
    19 / 106 (17.92%)
    21 / 107 (19.63%)
         occurrences all number
    18
    4
    3
    1
    6
    8
    19
    21
    Platelet count decreased
         subjects affected / exposed
    2 / 102 (1.96%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    1 / 101 (0.99%)
    0 / 104 (0.00%)
    2 / 106 (1.89%)
    8 / 107 (7.48%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    2
    8
    Injury, poisoning and procedural complications
    Subcutaneous haematoma
         subjects affected / exposed
    3 / 102 (2.94%)
    4 / 100 (4.00%)
    9 / 102 (8.82%)
    4 / 65 (6.15%)
    4 / 101 (3.96%)
    3 / 104 (2.88%)
    2 / 106 (1.89%)
    3 / 107 (2.80%)
         occurrences all number
    3
    4
    11
    4
    4
    3
    2
    3
    Post procedural haemorrhage
         subjects affected / exposed
    6 / 102 (5.88%)
    4 / 100 (4.00%)
    3 / 102 (2.94%)
    1 / 65 (1.54%)
    2 / 101 (1.98%)
    1 / 104 (0.96%)
    9 / 106 (8.49%)
    14 / 107 (13.08%)
         occurrences all number
    7
    4
    3
    1
    2
    1
    9
    14
    Incision site haemorrhage
         subjects affected / exposed
    1 / 102 (0.98%)
    3 / 100 (3.00%)
    4 / 102 (3.92%)
    2 / 65 (3.08%)
    3 / 101 (2.97%)
    2 / 104 (1.92%)
    5 / 106 (4.72%)
    7 / 107 (6.54%)
         occurrences all number
    1
    3
    4
    2
    3
    2
    5
    8
    Procedural pain
         subjects affected / exposed
    10 / 102 (9.80%)
    1 / 100 (1.00%)
    5 / 102 (4.90%)
    2 / 65 (3.08%)
    2 / 101 (1.98%)
    4 / 104 (3.85%)
    28 / 106 (26.42%)
    39 / 107 (36.45%)
         occurrences all number
    10
    1
    6
    2
    2
    5
    29
    40
    Post procedural swelling
         subjects affected / exposed
    5 / 102 (4.90%)
    3 / 100 (3.00%)
    4 / 102 (3.92%)
    2 / 65 (3.08%)
    4 / 101 (3.96%)
    2 / 104 (1.92%)
    10 / 106 (9.43%)
    10 / 107 (9.35%)
         occurrences all number
    5
    3
    4
    2
    4
    2
    10
    11
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    20 / 102 (19.61%)
    13 / 100 (13.00%)
    19 / 102 (18.63%)
    8 / 65 (12.31%)
    12 / 101 (11.88%)
    13 / 104 (12.50%)
    24 / 106 (22.64%)
    13 / 107 (12.15%)
         occurrences all number
    20
    14
    19
    8
    12
    13
    24
    13
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    7 / 102 (6.86%)
    0 / 100 (0.00%)
    6 / 102 (5.88%)
    7 / 65 (10.77%)
    0 / 101 (0.00%)
    6 / 104 (5.77%)
    4 / 106 (3.77%)
    0 / 107 (0.00%)
         occurrences all number
    7
    0
    6
    7
    0
    6
    5
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    4 / 102 (3.92%)
    1 / 100 (1.00%)
    4 / 102 (3.92%)
    3 / 65 (4.62%)
    2 / 101 (1.98%)
    3 / 104 (2.88%)
    8 / 106 (7.55%)
    14 / 107 (13.08%)
         occurrences all number
    5
    1
    4
    3
    2
    3
    8
    14
    Nausea
         subjects affected / exposed
    5 / 102 (4.90%)
    1 / 100 (1.00%)
    0 / 102 (0.00%)
    0 / 65 (0.00%)
    0 / 101 (0.00%)
    2 / 104 (1.92%)
    6 / 106 (5.66%)
    4 / 107 (3.74%)
         occurrences all number
    5
    1
    0
    0
    0
    2
    6
    4
    Vomiting
         subjects affected / exposed
    3 / 102 (2.94%)
    2 / 100 (2.00%)
    1 / 102 (0.98%)
    1 / 65 (1.54%)
    0 / 101 (0.00%)
    3 / 104 (2.88%)
    3 / 106 (2.83%)
    7 / 107 (6.54%)
         occurrences all number
    3
    2
    1
    1
    0
    3
    3
    7

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Mar 2018
    This global amendment comprised a modification of the randomization scheme to prevent unbalanzed arms, prohibited prior and concomittant medications (monoclonal antibodies not allowed) and inclusion criteria (pregancy test).

    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.
    There was no adjustment for multiplicity for comparisons between osocimab and comparators groups. The study was only powered for the comparison of osocimab with enoxaparin, thus no statistics is provided for apixaban and all safety endpoints.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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