<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/NCT03243175</url>
  </required_header>
  <id_info>
    <org_study_id>2016_77</org_study_id>
    <secondary_id>2017-004371-31</secondary_id>
    <nct_id>NCT03243175</nct_id>
  </id_info>
  <brief_title>Avoiding Anticoagulation After IntraCerebral Haemorrhage</brief_title>
  <acronym>A3ICH</acronym>
  <official_title>Avoiding Anticoagulation After IntraCerebral Haemorrhage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomised controlled trials (RCTs) demonstrate a substantial benefit from oral anticoagulant&#xD;
      drugs for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation&#xD;
      (AF). However, these RCTs excluded patients with prior intracerebral haemorrhage (ICH).&#xD;
      Therefore, guidelines are unable to recommend whether oral anticoagulant drugs, in particular&#xD;
      non-vitamin K antagonist (called direct OAC) - can be used for patients with AF after an&#xD;
      intracerebral haemorrhage.&#xD;
&#xD;
      Roughly 30% of adults with ICH have AF but in 2017 it remains unclear whether they should&#xD;
      start oral anticoagulant drugs, be treated with left atrial appendage closure (LAAC) or avoid&#xD;
      anticoagulation and LAAC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open label randomised controlled multicentre clinical trial with masked outcome assessment&#xD;
      (PROBE design) comparing 3 strategies (1:1:1): anticoagulation with a Direct OAC (Apixaban&#xD;
      5mgx2/day) vs avoid anticoagulation with left atrial appendage closure (LAAC) compared to&#xD;
      usual care (avoid anticoagulation).&#xD;
&#xD;
      Primary outcome: the net clinical benefit (composite outcome of major ischaemic and&#xD;
      haemorrhagic events) during a follow-up of 24 months (adjudication committee masked to the&#xD;
      randomisation arm&#xD;
&#xD;
      The results of A3ICH will help the clinician to decide which strategy is the most effective&#xD;
      in terms of benefit/risk ratio to prevent the risk of stroke or systemic embolism in patients&#xD;
      with a history of ICH and AF. A3ICH will address this increasingly common dilemma and could&#xD;
      affect clinical practice.&#xD;
&#xD;
      Data from A3ICH will contribute to an international individual patient data meta-analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 24, 2019</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>1:1:1</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>PROBE design</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events</measure>
    <time_frame>within 24 months after randomization.</time_frame>
    <description>The composite endpoint will enable to evaluate the net clinical benefit of the different therapeutic strategies.&#xD;
Definition of fatal event: when death is occurring within 30 days after the events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).</measure>
    <time_frame>at 12 and 24 months after randomization</time_frame>
    <description>fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death of any cause</measure>
    <time_frame>at 12 and 24 months after randomization</time_frame>
    <description>death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale</measure>
    <time_frame>at 12 and 24 months after randomization</time_frame>
    <description>functional dependence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EQ-5D (EuroQoL) Score</measure>
    <time_frame>at 12 and 24 months after randomization</time_frame>
    <description>health-related quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>neuroradiological biomarkers</measure>
    <time_frame>Baseline</time_frame>
    <description>on brain MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications of endovascular treatment</measure>
    <time_frame>up to 30 days</time_frame>
    <description>including device related complications</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Intracerebral Hemorrhage</condition>
  <condition>Atrial Fibrillation</condition>
  <condition>Microhaemorrhage</condition>
  <arm_group>
    <arm_group_label>Direct Oral Anticoagulant (DOAC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apixaban 5MG twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Left Atrial Appendage Closure (LAAC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Devices will be chosen by local teams.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>avoiding anticoagulation and LAAC during the entire study period The standard clinical practice without OAC may include: antiplatelet drug (in case of comorbidities such as coronary heart disease) or no antithrombotic drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban 5 MG</intervention_name>
    <description>Apixaban 5mg x 2 during 24 months</description>
    <arm_group_label>Direct Oral Anticoagulant (DOAC)</arm_group_label>
    <other_name>ELIQUIS 5mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>left atrial appendage closure</intervention_name>
    <description>left atrial appendage closure</description>
    <arm_group_label>Left Atrial Appendage Closure (LAAC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Adult (older than 18 years old, no upper age limit)&#xD;
&#xD;
          -  with a history of paroxysmal, persistent or long-standing non-valvular atrial&#xD;
             fibrillation (documented on an electrocardiogram)&#xD;
&#xD;
          -  and a CHA2DS2VASc score of 2 or more who have an indication for long-term&#xD;
             anticoagulation&#xD;
&#xD;
          -  who suffered from a spontaneous intracerebral haemorrhage (while being treated with&#xD;
             oral anticoagulants or not) documented with brain CT or MRI&#xD;
&#xD;
          -  more than 14 days before randomization (no upper delay limit)&#xD;
&#xD;
          -  for whom there is a clinical equipoise regarding the choice of the best preventive&#xD;
             strategy to avoid future vascular events.&#xD;
&#xD;
        Exclusion criteria for all treatment groups&#xD;
&#xD;
          -  Pre-randomisation modified Rankin score of 4 or 5&#xD;
&#xD;
          -  Conditions other than atrial fibrillation for which the patient requires long term&#xD;
             anticoagulation (for example prosthetic mechanical heart valve)&#xD;
&#xD;
          -  Serious bleeding events within the 6 months before randomisation (except for&#xD;
             intracerebral haemorrhage)&#xD;
&#xD;
          -  Life expectancy of less than 1 year&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
        Exclusion criteria related to the LAAC only&#xD;
&#xD;
          -  Contraindications due to local, anatomical reasons (such as thrombus in the left&#xD;
             atrial appendage, infection with a risk of endocarditis)&#xD;
&#xD;
          -  Patients older than 85 years&#xD;
&#xD;
          -  CHA2DS2VASc score of 2 or 3&#xD;
&#xD;
          -  Patient or attending physician are unwilling to undergo/perform intervention for LAAC&#xD;
&#xD;
        Exclusion criteria related to the Direct OAC only&#xD;
&#xD;
          -  Chronic renal insufficiency (clearance of creatinine by Cockcroft method &lt; 30ml/min)&#xD;
&#xD;
          -  Body weight lower than 50 kg&#xD;
&#xD;
          -  Allergy to apixaban&#xD;
&#xD;
          -  Coexisting conditions predisposing to head trauma (e.g. gait disturbances,&#xD;
             uncontrolled seizures disorders)&#xD;
&#xD;
          -  Patient or attending physician are unwilling to use of Direct OAC&#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>Charlotte Cordonnier, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Lille, Inserm, Univ Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Charlotte Cordonnier, MD, PhD</last_name>
    <phone>3 20 44 68 14</phone>
    <phone_ext>+33</phone_ext>
    <email>charlotte.cordonnier@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Roger Salengro, CHU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Charlottea Cordonnier, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>GHICL</name>
      <address>
        <city>Lomme</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Marta PASQUINI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH De Tourcoing</name>
      <address>
        <city>Tourcoing</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Frédéric DUMONT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>January 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>intracerebral hemorrhage</keyword>
  <keyword>atrial fibrillation</keyword>
  <keyword>microhemorrhage</keyword>
  <keyword>oral anticoagulation</keyword>
  <keyword>left atrial appendage closure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apixaban</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Prof Cordonnier (chief investigator of A3ICH) is a member of the international Collaboration Of Controlled Randomised trials of Oral Antithrombotic drugs after intraCranial Haemorrhage (COCROACH - coordination Prof Rustam Al-Shahi Salman, UK) working towards a pre-planned individual patient data meta-analysis</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
  </patient_data>
  <!-- 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/NCT03243175
org study id: 2016_77
secondary id: 2017-004371-31
nct id: NCT03243175
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Randomised controlled trials (RCTs) demonstrate a substantial benefit from oral anticoagulant
      drugs for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation
      (AF). However, these RCTs excluded patients with prior intracerebral haemorrhage (ICH).
      Therefore, guidelines are unable to recommend whether oral anticoagulant drugs, in particular
      non-vitamin K antagonist (called direct OAC) - can be used for patients with AF after an
      intracerebral haemorrhage.

      Roughly 30% of adults with ICH have AF but in 2017 it remains unclear whether they should
      start oral anticoagulant drugs, be treated with left atrial appendage closure (LAAC) or avoid
      anticoagulation and LAAC.
Open label randomised controlled multicentre clinical trial with masked outcome assessment
      (PROBE design) comparing 3 strategies (1:1:1): anticoagulation with a Direct OAC (Apixaban
      5mgx2/day) vs avoid anticoagulation with left atrial appendage closure (LAAC) compared to
      usual care (avoid anticoagulation).

      Primary outcome: the net clinical benefit (composite outcome of major ischaemic and
      haemorrhagic events) during a follow-up of 24 months (adjudication committee masked to the
      randomisation arm

      The results of A3ICH will help the clinician to decide which strategy is the most effective
      in terms of benefit/risk ratio to prevent the risk of stroke or systemic embolism in patients
      with a history of ICH and AF. A3ICH will address this increasingly common dilemma and could
      affect clinical practice.

      Data from A3ICH will contribute to an international individual patient data meta-analysis.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 1:1:1
primary purpose: Prevention
masking: Single (Outcomes Assessor)
masking description: PROBE design
measure: Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events
time frame: within 24 months after randomization.
description: The composite endpoint will enable to evaluate the net clinical benefit of the different therapeutic strategies.
Definition of fatal event: when death is occurring within 30 days after the events.
measure: Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
time frame: at 12 and 24 months after randomization
description: fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
measure: Death of any cause
time frame: at 12 and 24 months after randomization
description: death
measure: Modified Rankin Scale
time frame: at 12 and 24 months after randomization
description: functional dependence
measure: EQ-5D (EuroQoL) Score
time frame: at 12 and 24 months after randomization
description: health-related quality of life
measure: neuroradiological biomarkers
time frame: Baseline
description: on brain MRI
measure: Complications of endovascular treatment
time frame: up to 30 days
description: including device related complications
arm group label: Direct Oral Anticoagulant (DOAC)
arm group type: Experimental
description: Apixaban 5MG twice daily
arm group label: Left Atrial Appendage Closure (LAAC)
arm group type: Experimental
description: Devices will be chosen by local teams.
arm group label: Control
arm group type: No Intervention
description: avoiding anticoagulation and LAAC during the entire study period The standard clinical practice without OAC may include: antiplatelet drug (in case of comorbidities such as coronary heart disease) or no antithrombotic drug
intervention type: Drug
intervention name: Apixaban 5 MG
description: Apixaban 5mg x 2 during 24 months
arm group label: Direct Oral Anticoagulant (DOAC)
other name: ELIQUIS 5mg
intervention type: Device
intervention name: left atrial appendage closure
description: left atrial appendage closure
arm group label: Left Atrial Appendage Closure (LAAC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charlotte Cordonnier, MD, PhD
role: Principal Investigator
affiliation: University Hospital Lille, Inserm, Univ Lille
last name: Charlotte Cordonnier, MD, PhD
phone: 3 20 44 68 14
phone ext: +33
email: charlotte.cordonnier@chru-lille.fr
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: France
responsible party type: Sponsor
mesh term: Cerebral Hemorrhage
mesh term: Atrial Fibrillation
mesh term: Hemorrhage
mesh term: Apixaban
sharing ipd: Yes
ipd description: Prof Cordonnier (chief investigator of A3ICH) is a member of the international Collaboration Of Controlled Randomised trials of Oral Antithrombotic drugs after intraCranial Haemorrhage (COCROACH - coordination Prof Rustam Al-Shahi Salman, UK) working towards a pre-planned individual patient data meta-analysis
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)