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   43845   clinical trials with a EudraCT protocol, of which   7282   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:
    Anticoagulation using the direct factor Xa inhibitor apixaban during Atrial Fibrillation catheter Ablation: Comparison to vitamin K antagonist therapy.

    Summary
    EudraCT number
    		 2014-002442-45
    Trial protocol
    		 DE   BE   DK   GB   NL   ES   AT  
    Global end of trial date
    12 Sep 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 May 2022
    First version publication date
    27 May 2022
    Other versions
    Summary report(s)
    		 AXAFA-AFNET 5 Appendix 1
    AXAFA-AFNET 5 Appendix 2
    AXAFA-AFNET 5 Report Synopsis
    AXAFA-AFNET 5 Appendix 3

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AXAFA_AFNET5
    Additional study identifiers
    ISRCTN number
    		 ISRCTN87711003
    US NCT number
    		 NCT02227550
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Kompetenznetz Vorhofflimmern e.V. (AFNET) [Atrial Fibrillation NETwork]
    Sponsor organisation address
    Mendelstraße 11, Münster, Germany, 48149
    Public contact
    AFNET e.V., Kompetenznetz Vorhofflimmern e.V. (AFNET) [Atrial Fibrillation NETwork], +49 251 980 1340, info@kompetenznetz-vorhofflimmern.de
    Scientific contact
    AFNET e.V., Kompetenznetz Vorhofflimmern e.V. (AFNET) [Atrial Fibrillation NETwork], +49 251 980 1340, info@kompetenznetz-vorhofflimmern.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    11 Jan 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Sep 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that anticoagulation with the direct factor Xa inhibitor apixaban is not less safe than VKA therapy in patients undergoing catheter ablation of non-valvular AF in the prevention of peri-procedural complications.
    Protection of trial subjects
    Procedural safety was paramount in the context of AXAFA, and all means for a safe procedure were taken. The study was conducted in experienced centres on the plateau phase of their learning curve. Pre-study assessment of all centres guaranteed sufficient experience in PVI procedures. Evaluation of experimental or novel ablation devices was not permitted in the AXAFA trial. The exact ablation technique should follow local routine and adhere to the recommendations of the AFNET/EHRA/ECAS consensus statement on catheter ablation of AF, and to the locally applicable AF guidelines. Local routine should guide details of the procedure (e.g. the type of ablation and mapping system used, or the choice of ablation energy) within the limits of these recommendations.
    Background therapy
    		 All patients in AXAFA underwent catheter ablation of AF while on continued oral anticoagulation as described above. Silent brain lesions were assessed a sub-study by brain MRI 3-48 hours after the ablation procedure.
    Evidence for comparator
    		 To demonstrate that anticoagulation with the direct factor Xa inhibitor apixaban is not less safe than VKA therapy in patients undergoing catheter ablation of non-valvular AF in the prevention of peri-procedural complications. Patients randomised to the VKA group received oral anticoagulation using the locally used, marketed VKA, e.g. warfarin, phenprocoumon, acecoumarol, or fluindione. First intake of study medication was ensured at study enrolment (taking into consideration the change management instructions).
    Actual start date of recruitment
    27 Feb 2015
    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: 109
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    United Kingdom: 26
    Country: Number of subjects enrolled
    Austria: 33
    Country: Number of subjects enrolled
    Belgium: 135
    Country: Number of subjects enrolled
    Denmark: 138
    Country: Number of subjects enrolled
    Germany: 103
    Country: Number of subjects enrolled
    Italy: 67
    Country: Number of subjects enrolled
    United States: 28
    Worldwide total number of subjects
    674
    EEA total number of subjects
    620
    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)
    357
    From 65 to 84 years
    317
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment started on 27 February 2015 and ended on 10April 2017 and was performed in Austria, Belgium, Germany, Denmark, Spain, Great Britain, Italy, Netherlands and the USA.

    Pre-assignment
    Screening details
    		 The intended population for this study is patients scheduled for catheter ablation of AF. Patients will be recruited by contracted study sites only, i.e. by approximately 50 sites performing catheter ablation for AF in clinical routine.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Xa Group
    Arm description
    		 Patients randomised to the Xa group receive apixaban 5 mg twice daily throughout the study duration. Apixaban will be continued during the ablation procedure with twice daily dosing. The apixaban dose is be reduced to 2.5 mg twice daily in patients who fulfil two of the following criteria at the time of randomisation: (chronic kidney disease or 60 kg body weight or less or age 80 years or more).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Apixaban
    Investigational medicinal product code
    BMS-562247
    Other name
    Eliquis
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients randomised to the Xa group receive apixaban 5 mg twice daily throughout the study duration. Apixaban will be continued during the ablation procedure with twice daily dosing. The apixaban dose is be reduced to 2.5 mg twice daily in patients who fulfil two of the following criteria at the time of randomisation: (chronic kidney disease or 60 kg body weight or less or age 80 years or more).

    Arm title
    		 VKA group
    Arm description
    		 Patients randomised to the VKA group will receive oral anticoagulation using the locally used, marketed VKA, e.g. warfarin, phenprocoumon, acecoumarol, or fluindione. First intake of study medication needs to be ensured at study enrolment (taking into consideration the change management instructions). VKAs will be prescribed as in clinical routine and dispensed by local hospital pharmacy. VKA therapy will be monitored by INR measurements according to applicable medical guidelines and to local routine policy.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Vitamin K Antagonist
    Investigational medicinal product code
    Other name
    Warfarin, Phenprocoumon, Acecoumarol, Fluindione
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients randomised to the VKA group will receive oral anticoagulation using the locally used, marketed VKA, e.g. warfarin, phenprocoumon, acecoumarol, or fluindione. First intake of study medication needs to be ensured at study enrolment. VKA therapy will be monitored by INR measurements according to applicable medical guidelines and to local routine policy.

    Number of subjects in period 1
    		Xa Group VKA group
    Started
    338
    336
    Completed
    311
    308
    Not completed
    27
    28
         Adverse event, serious fatal
    5
    5
         Consent withdrawn by subject
    16
    19
         Lost to follow-up
    2
    -
         not specified
    4
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    overall trial
    Reporting group description
    		 -

    Reporting group values
    		 overall trial Total
    Number of subjects
    		 674 674
    Age categorical
    mITT population
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 357 357
        From 65-84 years
    		 317 317
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 221 221
        Male
    		 453 453
    Subject analysis sets

    Subject analysis set title
    mITT
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    mITT Population: patients who started study drug and had the index catheter ablation procedure performed

    Subject analysis sets values
    		 mITT
    Number of subjects
    633
    Age categorical
    mITT population
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    337
        From 65-84 years
    296
        85 years and over
    0
    Age continuous
    Units:
        
    ±
    Gender categorical
    Units: Subjects
        Female
    209
        Male
    424

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Xa Group
    Reporting group description
    		 Patients randomised to the Xa group receive apixaban 5 mg twice daily throughout the study duration. Apixaban will be continued during the ablation procedure with twice daily dosing. The apixaban dose is be reduced to 2.5 mg twice daily in patients who fulfil two of the following criteria at the time of randomisation: (chronic kidney disease or 60 kg body weight or less or age 80 years or more).

    Reporting group title
    VKA group
    Reporting group description
    		 Patients randomised to the VKA group will receive oral anticoagulation using the locally used, marketed VKA, e.g. warfarin, phenprocoumon, acecoumarol, or fluindione. First intake of study medication needs to be ensured at study enrolment (taking into consideration the change management instructions). VKAs will be prescribed as in clinical routine and dispensed by local hospital pharmacy. VKA therapy will be monitored by INR measurements according to applicable medical guidelines and to local routine policy.

    Subject analysis set title
    mITT
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    mITT Population: patients who started study drug and had the index catheter ablation procedure performed

    Primary: Patients with primary endpoint: composite of all-cause death, strike or major-bleeding

    		 Close Top of page
    End point title
    		 Patients with primary endpoint: composite of all-cause death, strike or major-bleeding
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of subjects
    22
    23
    Statistical analysis title
    		 Composite endpoint
    Comparison groups
    VKA group v Xa Group
    Number of subjects included in analysis
    633
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0002
    Method
    		 Farrington and Manning non-inferiority
    Confidence interval

    Primary: Death

    		 Close Top of page
    End point title
    		 Death [1]
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoint
    1
    1
    No statistical analyses for this end point

    Primary: Stroke or TIA

    		 Close Top of page
    End point title
    		 Stroke or TIA [2]
    End point description
    End point type
    Primary
    End point timeframe
    Oberalll-trial
    Notes
    [2] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoitns
    2
    0
    No statistical analyses for this end point

    Primary: Major Bleeding (BARC 2-5)

    		 Close Top of page
    End point title
    		 Major Bleeding (BARC 2-5) [3]
    End point description
    End point type
    Primary
    End point timeframe
    Over all trial
    Notes
    [3] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of outcomes
    20
    25
    No statistical analyses for this end point

    Primary: Bleeding requiring medical attention (BARC2)

    		 Close Top of page
    End point title
    		 Bleeding requiring medical attention (BARC2) [4]
    End point description
    End point type
    Primary
    End point timeframe
    Over all trial
    Notes
    [4] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    12
    12
    No statistical analyses for this end point

    Primary: Bleeding with haemoglobin drop of 30 to < 50 g/L or requiring transfusion (BARC 3a)

    		 Close Top of page
    End point title
    		 Bleeding with haemoglobin drop of 30 to < 50 g/L or requiring transfusion (BARC 3a) [5]
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    Notes
    [5] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    5
    4
    No statistical analyses for this end point

    Primary: Bleeding with haemoglobin drop >= 50 g/L, or requiring surgery or iv vasoactive agents , or cardiac tamponade (BARC 3b)

    		 Close Top of page
    End point title
    		 Bleeding with haemoglobin drop >= 50 g/L, or requiring surgery or iv vasoactive agents , or cardiac tamponade (BARC 3b) [6]
    End point description
    End point type
    Primary
    End point timeframe
    Over all trial
    Notes
    [6] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    3
    8
    No statistical analyses for this end point

    Primary: Intracranial haemorrhage (BARC 3c)

    		 Close Top of page
    End point title
    		 Intracranial haemorrhage (BARC 3c) [7]
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    Notes
    [7] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    318
    Units: Number of endpoints
    0
    1
    No statistical analyses for this end point

    Primary: TIMI major bleeding (Intracranial bleed, or bleeding resulting in a haemoglobin drop of >= 50 g/L, or bleeding resulting in death within 7 days)

    		 Close Top of page
    End point title
    		 TIMI major bleeding (Intracranial bleed, or bleeding resulting in a haemoglobin drop of >= 50 g/L, or bleeding resulting in death within 7 days) [8]
    End point description
    End point type
    Primary
    End point timeframe
    overall trial
    Notes
    [8] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    1
    3
    No statistical analyses for this end point

    Primary: ISTH major bleeeding

    		 Close Top of page
    End point title
    		 ISTH major bleeeding [9]
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    Notes
    [9] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    10
    14
    No statistical analyses for this end point

    Primary: Tamponade (Clinical type of bleeding event)

    		 Close Top of page
    End point title
    		 Tamponade (Clinical type of bleeding event) [10]
    End point description
    End point type
    Primary
    End point timeframe
    Over all trial
    Notes
    [10] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    2
    5
    No statistical analyses for this end point

    Primary: Acces site bleed (Clinical type of bleeding event)

    		 Close Top of page
    End point title
    		 Acces site bleed (Clinical type of bleeding event) [11]
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    Notes
    [11] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    12
    15
    No statistical analyses for this end point

    Primary: Bleeding requiring transfusion of red blood cells (clinical type of bleeding event)

    		 Close Top of page
    End point title
    		 Bleeding requiring transfusion of red blood cells (clinical type of bleeding event) [12]
    End point description
    End point type
    Primary
    End point timeframe
    overall trial
    Notes
    [12] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Number of endpoints
    2
    1
    No statistical analyses for this end point

    Primary: Other major bleed (Clinical type of bleeding event)

    		 Close Top of page
    End point title
    		 Other major bleed (Clinical type of bleeding event) [13]
    End point description
    End point type
    Primary
    End point timeframe
    Overall trial
    Notes
    [13] - 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: Statistical analysis data provided for composite endpoint
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: NUmber of Endpoints
    5
    2
    No statistical analyses for this end point

    Secondary: time from randomization to ablation days, median (q1, q3)

    		 Close Top of page
    End point title
    		 time from randomization to ablation days, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: days
        median (inter-quartile range (Q1-Q3))
    34.0 (18.0 to 48.0)
    36 (21 to 52.0)
    No statistical analyses for this end point

    Secondary: Nights spent in hiospital after index ablation, median (q1, q3)

    		 Close Top of page
    End point title
    		 Nights spent in hiospital after index ablation, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: Nights
        median (inter-quartile range (Q1-Q3))
    2 (1 to 5)
    3 (2 to 7)
    No statistical analyses for this end point

    Secondary: ACT during ablation, seconds, median (q1, q3)

    		 Close Top of page
    End point title
    		 ACT during ablation, seconds, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: seconds
        median (inter-quartile range (Q1-Q3))
    310.0 (273.0 to 350.0)
    348.5 (304.0 to 396.0)
    No statistical analyses for this end point

    Secondary: Number of subjects with at least one ACT value <250(n)

    		 Close Top of page
    End point title
    		 Number of subjects with at least one ACT value <250(n)
    End point description
    End point type
    Secondary
    End point timeframe
    overal trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    316
    315
    Units: Number of subjects
    130
    84
    No statistical analyses for this end point

    Secondary: Number of subjects with all ACT values in range (n)

    		 Close Top of page
    End point title
    		 Number of subjects with all ACT values in range (n)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    316
    315
    Units: Number of subjects
    73
    161
    No statistical analyses for this end point

    Secondary: Number of subjects with at least one ACT value <300(n)

    		 Close Top of page
    End point title
    		 Number of subjects with at least one ACT value <300(n)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    316
    315
    Units: Number of subjects
    243
    154
    No statistical analyses for this end point

    Secondary: number of bleeding events (n)

    		 Close Top of page
    End point title
    		 number of bleeding events (n)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    318
    315
    Units: number of events
    54
    64
    No statistical analyses for this end point

    Secondary: Patients without recurrence of atrial fibrillation (n)

    		 Close Top of page
    End point title
    		 Patients without recurrence of atrial fibrillation (n)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    311
    308
    Units: number of patients
    217
    217
    No statistical analyses for this end point

    Secondary: SF-12 physical components score at end of study, median (q1, q3)

    		 Close Top of page
    End point title
    		 SF-12 physical components score at end of study, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    289
    275
    Units: SF-12 score
        median (inter-quartile range (Q1-Q3))
    48.4 (41.9 to 54.2)
    48.8 (42.2 to 54.4)
    No statistical analyses for this end point

    Secondary: Change in SF-12 physical component score at end of study compared to baseline (d PCS), median (q1, q3)

    		 Close Top of page
    End point title
    		 Change in SF-12 physical component score at end of study compared to baseline (d PCS), median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    280
    267
    Units: change in score
        median (inter-quartile range (Q1-Q3))
    2.4 (-2.2 to 7.9)
    2.8 (-2.0 to 8.3)
    No statistical analyses for this end point

    Secondary: SF-12 mental component score at end of study, median (q1, q3)

    		 Close Top of page
    End point title
    		 SF-12 mental component score at end of study, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    290
    267
    Units: SF-12 mental componen t score
        median (inter-quartile range (Q1-Q3))
    54.2 (45.8 to 58.3)
    54.5 (46.6 to 59.7)
    No statistical analyses for this end point

    Secondary: Change in SF-12 mental component score at end of study compared to baseline (d MCS) n(%), median (q1, q3)

    		 Close Top of page
    End point title
    		 Change in SF-12 mental component score at end of study compared to baseline (d MCS) n(%), median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    281
    267
    Units: Change in SF-12 score
        median (inter-quartile range (Q1-Q3))
    0.4 (-3.6 to 8.0)
    1.6 (-2.8 to 8.3)
    No statistical analyses for this end point

    Secondary: Karnofsky score at end of study, median (q1, q3)

    		 Close Top of page
    End point title
    		 Karnofsky score at end of study, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    311
    308
    Units: Karnofsky score
        median (inter-quartile range (Q1-Q3))
    100 (90 to 100)
    100 (90 to 100)
    No statistical analyses for this end point

    Secondary: Change in Karnofsky score at end of study compared to baseline (dKarnofsky), median (q1, q3)

    		 Close Top of page
    End point title
    		 Change in Karnofsky score at end of study compared to baseline (dKarnofsky), median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    311
    308
    Units: Change in Karnofsky sccore
        median (inter-quartile range (Q1-Q3))
    10 (0 to 10)
    10 (0 to 10)
    No statistical analyses for this end point

    Secondary: Cognitive function at end of study (MoCA), median (q1, q3)

    		 Close Top of page
    End point title
    		 Cognitive function at end of study (MoCA), median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    305
    302
    Units: MoCA score
        median (inter-quartile range (Q1-Q3))
    28.0 (26.0 to 29.0)
    28.0 (26.0 to 29.0)
    No statistical analyses for this end point

    Secondary: Abnormal MoCA at baseline (<26), n

    		 Close Top of page
    End point title
    		 Abnormal MoCA at baseline (<26), n
    End point description
    End point type
    Secondary
    End point timeframe
    Overall time
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    305
    302
    Units: Subjects
    75
    66
    No statistical analyses for this end point

    Secondary: Change in MoCA at end of study compared to baseline, median (q1, q3)

    		 Close Top of page
    End point title
    		 Change in MoCA at end of study compared to baseline, median (q1, q3)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    301
    296
    Units: change in MoCA
        median (inter-quartile range (Q1-Q3))
    0.0 (-1.0 to 2.0)
    1.0 (-1.0 to 2.0)
    No statistical analyses for this end point

    Secondary: Change in patients with abnormal MoCA at end of study compared to baseline, n (%)

    		 Close Top of page
    End point title
    		 Change in patients with abnormal MoCA at end of study compared to baseline, n (%)
    End point description
    End point type
    Secondary
    End point timeframe
    overall trial
    End point values
    		 Xa Group VKA group
    Number of subjects analysed
    305
    302
    Units: change in MoCA score
        number (not applicable)
    -5.1
    -9.2
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    30.03.2015 - 18.08.2017
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Vitamin K Antagonist
    Reporting group description
    		 All randomized patients who received VKA

    Reporting group title
    Apixaban
    Reporting group description
    		 All randomized patients who started Apixaban

    Serious adverse events
    		 Vitamin K Antagonist Apixaban
    Total subjects affected by serious adverse events
         subjects affected / exposed
    93 / 327 (28.44%)
    88 / 328 (26.83%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    1
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    2 / 327 (0.61%)
    4 / 328 (1.22%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 327 (0.61%)
    3 / 328 (0.91%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    2 / 327 (0.61%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aneurysm
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         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 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cardioversion
         subjects affected / exposed
    10 / 327 (3.06%)
    11 / 328 (3.35%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac ablation
         subjects affected / exposed
    5 / 327 (1.53%)
    3 / 328 (0.91%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac pacemaker insertion
         subjects affected / exposed
    2 / 327 (0.61%)
    3 / 328 (0.91%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Percutaneous coronary intervention
         subjects affected / exposed
    2 / 327 (0.61%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transfusion
         subjects affected / exposed
    2 / 327 (0.61%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot amputation
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia repair
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip arthroplasty
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastectomy
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device implantation
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast operation
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Catheter site haemorrhage
         subjects affected / exposed
    15 / 327 (4.59%)
    11 / 328 (3.35%)
         occurrences causally related to treatment / all
    8 / 17
    8 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    4 / 327 (1.22%)
    4 / 328 (1.22%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    Pyrexia
         subjects affected / exposed
    2 / 327 (0.61%)
    3 / 328 (0.91%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sensation of foreign body
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Coagulation time abnormal
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram change
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         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
    Vascular pseudoaneurysm
         subjects affected / exposed
    10 / 327 (3.06%)
    6 / 328 (1.83%)
         occurrences causally related to treatment / all
    5 / 12
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burn oesophageal
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    31 / 327 (9.48%)
    21 / 328 (6.40%)
         occurrences causally related to treatment / all
    0 / 40
    0 / 24
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    Cardiac failure
         subjects affected / exposed
    2 / 327 (0.61%)
    8 / 328 (2.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    2 / 327 (0.61%)
    7 / 328 (2.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Percardial haemorrhage
         subjects affected / exposed
    5 / 327 (1.53%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    2 / 327 (0.61%)
    4 / 328 (1.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    3 / 327 (0.92%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 327 (0.31%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atriventricular block
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    2 / 327 (0.61%)
    4 / 328 (1.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 327 (0.31%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    2 / 327 (0.61%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    2 / 327 (0.61%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phrenic nerve paralysis
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    2 / 327 (0.61%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 327 (0.31%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb discomfort
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (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
    Pneumonia
         subjects affected / exposed
    8 / 327 (2.45%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    2 / 327 (0.61%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (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
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Vitamin K Antagonist Apixaban
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    34 / 327 (10.40%)
    44 / 328 (13.41%)
    Vascular disorders
    Groin hematoma
         subjects affected / exposed
    11 / 327 (3.36%)
    15 / 328 (4.57%)
         occurrences all number
    11
    15
    Major bleed
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Bleeding varicose vein
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    Electrical cardioversion
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Nonspecific chest pain
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Ankle edema
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Fatigue aggravated
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Fever
         subjects affected / exposed
    3 / 327 (0.92%)
    0 / 328 (0.00%)
         occurrences all number
    3
    0
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences all number
    0
    2
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Nasal mucus blood tinged
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Nose bleed
         subjects affected / exposed
    3 / 327 (0.92%)
    2 / 328 (0.61%)
         occurrences all number
    3
    2
    Investigations
    Electrocardiogram ST segment elevation
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Echocardiogram abnormal
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Arterial catheterisation abnormal
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Post procedural bleeding
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Eyelid haematoma
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Atrial tachycardia
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences all number
    1
    1
    Atrial fibrillation
         subjects affected / exposed
    1 / 327 (0.31%)
    2 / 328 (0.61%)
         occurrences all number
    1
    2
    Palpitations
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 327 (0.61%)
    0 / 328 (0.00%)
         occurrences all number
    2
    0
    Phrenic nerve paralysis
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences all number
    0
    2
    Migraine
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences all number
    0
    2
    Syncope
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Eye haemorrhage
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Anal bleeding
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Defaecation frequncy inceased
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 327 (0.00%)
    2 / 328 (0.61%)
         occurrences all number
    0
    2
    Oesophageal discomfort
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences all number
    1
    1
    Gastric disorder
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Gastric hypomotility
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Gingival bleeding
         subjects affected / exposed
    1 / 327 (0.31%)
    1 / 328 (0.30%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    0 / 327 (0.00%)
    1 / 328 (0.30%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0
    Tendon calcification
         subjects affected / exposed
    1 / 327 (0.31%)
    0 / 328 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Dec 2014
    • Patients can undergo catheter ablation within the trial after at least 30 days of continuous effective anticoagulation or earlier when atrial thrombi have been excluded by a clinically indicated TEE. It was added that a TEE performed within 6 hours prior to randomisation is considered valid. • A new appendix was added (Appendix VIII “List of strong inducers/inhibitors of P-gp and CYP3A4 which lead to contraindication for the combined use with apixaban”) following a primary Ethics Committee’s request. • A new exclusion criterion was added (E14 “Documented atrial thrombi less than 3 months prior to randomisation.”) following a primary Ethics Committee’s request. • Following a Competent Authority’s request it was added that women of childbearing potential are required to perform a pregnancy test before first intake of the study medication. If clinical signs of pregnancy are present during intake of the study medication and up to an adequate interval after intake of study medication, a pregnancy test has to be performed. • In accordance with the SmPC of apixaban and following a Competent Authority’s request it was added that liver function parameters have to be assessed prior to first intake of study medication. • More precise criteria for assessment of continuous effective anticoagulation in VKA patients prior to index catheter ablation (i.e. at least one INR value ≥2.0 prior to ablation and thereafter no value <2.0 prior to ablation). • The list of conditions for which a patient is not to undergo MRI was extended following a primary Ethics Committee’s request.
    08 Jan 2015
    • Wording in section “Adverse Event Reporting” was adjusted following a Competent Authority’s request. • Further it was specified that in addition to serious adverse events (SAEs), also “AEs of special interest” will be MedDRA coded.
    20 Feb 2015
    • Following a Competent Authority’s request correction of reporting period for SAEs in accordance with ENTR/CT-3 (2011/C 172/01).
    21 Jul 2016
    Final valid US version: • The term “exploratory” in the context of primary outcome and secondary endpoints was deleted following a primary Ethics Committee’s request. • Protocol sections “Sample Size and Power Calculation” and “Interim Analyses, Reassessment of the Sample Size” have been described more in detail following a primary Ethics Committee’s enquiries. • Criteria for assessment of continuous effective anticoagulation in VKA patients prior to index catheter ablation was adapted: Because in clinical routine an INR value ≥2 directly prior to catheter ablation is often not achieved, the reduction of the minimum value of the last INR required prior to the index catheter ablation to ≥1.8 represents clinical practice better. Further requirement of documenting all INR measurements (minimum of three) was added to ensure continuous anticoagulation. • More concise description of the first intake of study medication was added in order to avoid misunderstandings. • Clarification according to the definition of SAEs and AEs judged as medically important events. • Modified Rankin Scale at baseline visit added and corresponding protocol appendix IX. • Specification with regard to procedure assessing for pericardial effusion after catheter ablation, i.e. instead of a transthoracic echocardiography (TTE) also an intracardiac echocardiography (ICE) can be performed.
    02 Nov 2016
    Final EU version: • The term “exploratory” in the context of primary outcome and secondary endpoints was deleted following a primary Ethics Committee’s request. • Protocol sections “Sample Size and Power Calculation” and “Interim Analyses, Reassessment of the Sample Size” have been described more in detail following a primary Ethics Committee’s enquiries. • Criteria for assessment of continuous effective anticoagulation in VKA patients prior to index catheter ablation was adapted: Because in clinical routine an INR value ≥2 directly prior to catheter ablation is often not achieved, the reduction of the minimum value of the last INR required prior to the index catheter ablation to ≥1.8 represents clinical practice better. Further requirement of documenting all INR measurements (minimum of three) was added to ensure continuous anticoagulation. • More concise description of the first intake of study medication was added in order to avoid misunderstandings. • Clarification according to the definition of SAEs and AEs judged as medically important events. • Modified Rankin Scale at baseline visit added and corresponding protocol appendix IX. • Specification with regard to procedure assessing for pericardial effusion after catheter ablation, i.e. instead of a transthoracic echocardiography (TTE) also an intracardiac echocardiography (ICE) can be performed. • Following a Competent Authority’s objection the wording in section “Adverse Event Reporting” has again been formulated as in the version of amendment 08.01.2015.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29579168
    http://www.ncbi.nlm.nih.gov/pubmed/28130378
    http://www.ncbi.nlm.nih.gov/pubmed/32142113
    http://www.ncbi.nlm.nih.gov/pubmed/32725107
    http://www.ncbi.nlm.nih.gov/pubmed/33046527
    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-Thu Apr 18 19:59:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA