<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02227550</url>
  </required_header>
  <id_info>
    <org_study_id>AFNET 5 AXAFA</org_study_id>
    <secondary_id>2014-002442-45</secondary_id>
    <nct_id>NCT02227550</nct_id>
  </id_info>
  <brief_title>Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy</brief_title>
  <acronym>AXAFA</acronym>
  <official_title>An Investigator-driven, Prospective, Parallel-group, Randomised, Open, Blinded Outcome Assessment (PROBE), Multi-centre Trial to Determine the Optimal Anticoagulation Therapy for Patients Untergoing Catheter Ablation of Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Atrial Fibrillation Network</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Atrial Fibrillation Network</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study objective is to demonstrate that anticoagulation with the direct factor Xa inhibitor&#xD;
      apixaban is not less safe than Vitamin-K-antagonists (VKA) therapy in patients undergoing&#xD;
      catheter ablation of non-valvular AF in the prevention of peri-procedural complications.&#xD;
&#xD;
      The AXAFA trial will compare peri-ablational treatment with apixaban to peri-ablational&#xD;
      treatment wit VKA in a randomized trial of patients undergoing catheter ablation of atrial&#xD;
      fibrillation (AF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AXAFA is an open-label trial designed to evaluate the safety and efficacy of two types of&#xD;
      anticoagulant therapy, VKA therapy and therapy with the direct factor Xa inhibitor apixaban,&#xD;
      in patients undergoing scheduled catheter ablation for AF. All patients will undergo the&#xD;
      ablation procedure after pre-treatment with an anticoagulant (either apixaban in the &quot;Xa&#xD;
      group&quot; or a vitamin K antagonist in the &quot;VKA group&quot;).&#xD;
&#xD;
      Patients can undergo catheter ablation within the trial after at least 30 days of continuous&#xD;
      effective anticoagulation. Ablation can be performed earlier when or timely after exclusion&#xD;
      of atrial thrombi have been excluded by a clinically indicated by transthoracic&#xD;
      echocardioggram (TEE). After TEE continuous effective anticoagulation must be ensured until&#xD;
      the end of the trial.&#xD;
&#xD;
      In the MRI-substudy will be explored wether novel oral anticoagulants (NOAC) have the&#xD;
      potential to reduce clinically silent brain lesions after catheter ablation of AF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">April 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>death and serious cardiovascular events</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>A composite of all-cause death, stroke (ischemic stroke, subarachnoid haemorrhage and haemorrhagic stroke), and major bleeding events, def.as BARC 2 or higher</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>any bleeding event</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>major bleeding events acc. to the ISTH and TIMI definitions</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>strokes, other systemic embolic events and all-cause death</measure>
    <time_frame>appr. 4 month</time_frame>
    <description>number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time from randomisation to ablation</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number of days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nights spent in hospital after ablation</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>health-care related cost calculation</measure>
    <time_frame>appr. 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hospitalizations for cardiovascular reasons</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment duration prior to ablation and total time on oral anticoagulation</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number of days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>patients with clinically indicated TEE</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number of patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ACT during ablation</measure>
    <time_frame>during ablation</time_frame>
    <description>Active clotting measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>recurrent Atrial Fibrillation (AF)</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>time to recurrent AF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rhythm status at the end of follow-up</measure>
    <time_frame>end of follow-up</time_frame>
    <description>rythm status documented by 24 hour Holter ECG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>vascular access complications leading to prolongation of in-hospital stay or specific therapy</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>number of events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality-of-life changes</measure>
    <time_frame>baseline to 3 month follow-up</time_frame>
    <description>questionaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cognitive function change</measure>
    <time_frame>baseline to 3 month follow-up</time_frame>
    <description>questionaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinically &quot;silent&quot; MRI-detected brain lesions</measure>
    <time_frame>within 48 hours after ablation procedures</time_frame>
    <description>prevalence (MRI-substudy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally &quot;silent&quot; acute brain lesions on cognitive function after ablation</measure>
    <time_frame>appr. 4 months</time_frame>
    <description>MRI-substudy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">676</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Apixaban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin K antagonist</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin K antagonist</intervention_name>
    <description>any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin</description>
    <arm_group_label>Vitamin K antagonist</arm_group_label>
    <other_name>warfarin</other_name>
    <other_name>phenprocoumon</other_name>
    <other_name>acecoumaril</other_name>
    <other_name>fluindione</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban</intervention_name>
    <description>factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose) dose reduction Apixaban 2,5 mg twice daily in patients who fulfill tow of the following criteria at the time of randomisation: chronic kidney disease (serum creatine &gt;= 1.5 mg/dl (133mM), &lt;= 60 kg body weight or age &gt;= 80 years.</description>
    <arm_group_label>Apixaban</arm_group_label>
    <other_name>BMS-562247</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        I1. Non-valvular AF (ECG-documented) with a clinical indication for catheter ablation&#xD;
&#xD;
        I2. Clinical indication to undergo catheter ablation on continuous anticoagulant therapy&#xD;
&#xD;
        I3. Presence of at least one of the CHADS2 stroke risk factors&#xD;
&#xD;
          -  Stroke or TIA&#xD;
&#xD;
          -  age ≥ 75 years,&#xD;
&#xD;
          -  hypertension, defined as chronic treatment for hypertension, estimated need for&#xD;
             continuous antihypertensive therapy or resting blood pressure &gt; 145/90 mm Hg,&#xD;
&#xD;
          -  diabetes mellitus,&#xD;
&#xD;
          -  symptomatic heart failure (NYHA ≥ II).&#xD;
&#xD;
        I4. Age ≥ 18 years&#xD;
&#xD;
        I5. Provision of signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General exclusion criteria&#xD;
&#xD;
        E1. Any disease that limits life expectancy to less than 1 year&#xD;
&#xD;
        E2. Participation in another clinical trial, either within the past two months or still&#xD;
        ongoing&#xD;
&#xD;
        E3. Previous participation in AXAFA&#xD;
&#xD;
        E4. Pregnant women or women of childbearing potential not on adequate birth control: only&#xD;
        women with a highly effective method of contraception (oral contraception or intra-uterine&#xD;
        device) or sterile women can be randomised.&#xD;
&#xD;
        E5. Breastfeeding women&#xD;
&#xD;
        E6. Drug abuse or clinically manifest alcohol abuse&#xD;
&#xD;
        E7. Any stroke within 14 days before randomisation&#xD;
&#xD;
        E8. Coadministration with drugs that are strong dual inhibitors of cytochrome P450 3A4&#xD;
        (CYP3A4) and P-glycoprotein (P-gp) or strong dual inducers of CYP3A4 and P-gp (Appendix&#xD;
        VIII).&#xD;
&#xD;
        Exclusion criteria related to a cardiac condition&#xD;
&#xD;
        E9. Valvular AF (as defined by the focussed update of the ESC guidelines on AF, i.e. severe&#xD;
        mitral valve stenosis, mechanical heart valve). Furthermore, patients who underwent mitral&#xD;
        valve repair are not eligible for AXAFA.&#xD;
&#xD;
        E10. Any previous ablation or surgical therapy for AF&#xD;
&#xD;
        E11. Cardiac ablation therapy for any indication (catheter-based or surgical) within 3&#xD;
        months prior to randomisation&#xD;
&#xD;
        E12. Clinical need for &quot;triple therapy&quot; (combination therapy of clopidogrel,&#xD;
        acetylsalicylic acid, and oral anticoagulation)&#xD;
&#xD;
        E13. Other contraindications for use of VKA or apixaban&#xD;
&#xD;
        E14. Documented atrial thrombi less than 3 months prior to randomisation.&#xD;
&#xD;
        Exclusion criteria based on laboratory abnormalities&#xD;
&#xD;
        E15. Severe chronic kidney disease with an estimated glomerular filtration rate (GFR) &lt; 15&#xD;
        ml/min&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paulus Kirchhof, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of the University of Pennsyvlania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Cardiac Arrhythmia Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sentara Cariovascular Research Insititute</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>4 Sites</name>
      <address>
        <city>Different</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>5 Sites</name>
      <address>
        <city>Different</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>5 Sites</name>
      <address>
        <city>Different</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>13 Sites</name>
      <address>
        <city>Different</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>4 Sites</name>
      <address>
        <city>Different</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>6 Sites</name>
      <address>
        <city>Different</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>3 Sites</name>
      <address>
        <city>Different</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>4 Sites</name>
      <address>
        <city>Different</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Di Biase L, Callans D, Haeusler KG, Hindricks G, Al-Khalidi H, Mont L, Cosedis Nielsen J, Piccini JP, Schotten U, Kirchhof P. Rationale and design of AXAFA-AFNET 5: an investigator-initiated, randomized, open, blinded outcome assessment, multi-centre trial to comparing continuous apixaban to vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation. Europace. 2017 Jan;19(1):132-138. doi: 10.1093/europace/euw368.</citation>
    <PMID>28130378</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>June 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>October 19, 2017</last_update_submitted>
  <last_update_submitted_qc>October 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Atrilal fibrillation</keyword>
  <keyword>anticoagulation</keyword>
  <keyword>prevention of peri-procedural complication</keyword>
  <keyword>catheter ablation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin K</mesh_term>
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Apixaban</mesh_term>
    <mesh_term>Phenprocoumon</mesh_term>
    <mesh_term>Fluindione</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02227550
org study id: AFNET 5 AXAFA
secondary id: 2014-002442-45
nct id: NCT02227550
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Study objective is to demonstrate that anticoagulation with the direct factor Xa inhibitor
      apixaban is not less safe than Vitamin-K-antagonists (VKA) therapy in patients undergoing
      catheter ablation of non-valvular AF in the prevention of peri-procedural complications.

      The AXAFA trial will compare peri-ablational treatment with apixaban to peri-ablational
      treatment wit VKA in a randomized trial of patients undergoing catheter ablation of atrial
      fibrillation (AF).
AXAFA is an open-label trial designed to evaluate the safety and efficacy of two types of
      anticoagulant therapy, VKA therapy and therapy with the direct factor Xa inhibitor apixaban,
      in patients undergoing scheduled catheter ablation for AF. All patients will undergo the
      ablation procedure after pre-treatment with an anticoagulant (either apixaban in the "Xa
      group" or a vitamin K antagonist in the "VKA group").

      Patients can undergo catheter ablation within the trial after at least 30 days of continuous
      effective anticoagulation. Ablation can be performed earlier when or timely after exclusion
      of atrial thrombi have been excluded by a clinically indicated by transthoracic
      echocardioggram (TEE). After TEE continuous effective anticoagulation must be ensured until
      the end of the trial.

      In the MRI-substudy will be explored wether novel oral anticoagulants (NOAC) have the
      potential to reduce clinically silent brain lesions after catheter ablation of AF.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: death and serious cardiovascular events
time frame: appr. 4 months
description: A composite of all-cause death, stroke (ischemic stroke, subarachnoid haemorrhage and haemorrhagic stroke), and major bleeding events, def.as BARC 2 or higher
measure: any bleeding event
time frame: appr. 4 months
description: number
measure: major bleeding events acc. to the ISTH and TIMI definitions
time frame: appr. 4 months
description: number
measure: strokes, other systemic embolic events and all-cause death
time frame: appr. 4 month
description: number
measure: time from randomisation to ablation
time frame: appr. 4 months
description: number of days
measure: nights spent in hospital after ablation
time frame: appr. 4 months
description: number
measure: health-care related cost calculation
time frame: appr. 4 months
measure: hospitalizations for cardiovascular reasons
time frame: appr. 4 months
description: number
measure: Treatment duration prior to ablation and total time on oral anticoagulation
time frame: appr. 4 months
description: number of days
measure: patients with clinically indicated TEE
time frame: appr. 4 months
description: number of patients
measure: ACT during ablation
time frame: during ablation
description: Active clotting measurements
measure: recurrent Atrial Fibrillation (AF)
time frame: appr. 4 months
description: time to recurrent AF
measure: rhythm status at the end of follow-up
time frame: end of follow-up
description: rythm status documented by 24 hour Holter ECG
measure: vascular access complications leading to prolongation of in-hospital stay or specific therapy
time frame: appr. 4 months
description: number of events
measure: Quality-of-life changes
time frame: baseline to 3 month follow-up
description: questionaire
measure: cognitive function change
time frame: baseline to 3 month follow-up
description: questionaire
measure: clinically "silent" MRI-detected brain lesions
time frame: within 48 hours after ablation procedures
description: prevalence (MRI-substudy)
measure: Impact of ablation-associated clinically overt strokes or MRI-detected bus clincally "silent" acute brain lesions on cognitive function after ablation
time frame: appr. 4 months
description: MRI-substudy
arm group label: Apixaban
arm group type: Experimental
description: Xa group: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose)
arm group label: Vitamin K antagonist
arm group type: Active Comparator
description: VKA group: any Vitamin K antagonist (VKA), INR 2-3 , min. 30 days prescribed as in clinical routine
intervention type: Drug
intervention name: Vitamin K antagonist
description: any locally used VKA, INR 2-3, min. 30 days according to aplicable medical guidelines and local clinical routin
arm group label: Vitamin K antagonist
other name: warfarin
other name: phenprocoumon
other name: acecoumaril
other name: fluindione
intervention type: Drug
intervention name: Apixaban
description: factor Xa inhibitor Apixaban min. 30 days 5 mg twice daily (fix dose) dose reduction Apixaban 2,5 mg twice daily in patients who fulfill tow of the following criteria at the time of randomisation: chronic kidney disease (serum creatine >= 1.5 mg/dl (133mM), <= 60 kg body weight or age >= 80 years.
arm group label: Apixaban
other name: BMS-562247
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paulus Kirchhof, Professor
role: Principal Investigator
affiliation: University of Birmingham Centre for Cardiovascular Scienes, UK and University Hospital Muenster, Germany
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Belgium
country: Denmark
country: Germany
country: Italy
country: Netherlands
country: Spain
country: United Kingdom
country: United States
citation: Di Biase L, Callans D, Haeusler KG, Hindricks G, Al-Khalidi H, Mont L, Cosedis Nielsen J, Piccini JP, Schotten U, Kirchhof P. Rationale and design of AXAFA-AFNET 5: an investigator-initiated, randomized, open, blinded outcome assessment, multi-centre trial to comparing continuous apixaban to vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation. Europace. 2017 Jan;19(1):132-138. doi: 10.1093/europace/euw368.
PMID: 28130378
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Vitamin K
mesh term: Warfarin
mesh term: Apixaban
mesh term: Phenprocoumon
mesh term: Fluindione