<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/NCT04435418</url>
  </required_header>
  <id_info>
    <org_study_id>Version 1.0 September 30, 2016</org_study_id>
    <nct_id>NCT04435418</nct_id>
  </id_info>
  <brief_title>Eliquis Acute Stroke Safety Evaluation</brief_title>
  <acronym>EASSE</acronym>
  <official_title>Eliquis Acute Stroke Safety Evaluation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alberta</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Design:&#xD;
&#xD;
      This is an investigator-initiated prospective, open label, single arm phase IV study.&#xD;
      Patients with documented non-valvular atrial fibrillation (AF) with acute TIA (defined as&#xD;
      acute focal neurological deficits, with complete resolution of symptoms within 24 h of onset)&#xD;
      or ischemic stroke, irrespective of infarct volume or clinical severity will be enrolled.&#xD;
&#xD;
      Study Aim and Objectives:&#xD;
&#xD;
      The overall aim of this study is to demonstrate the feasibility and safety of initiating&#xD;
      apixaban therapy within 14 days of TIA or ischemic stroke regardless of the size and severity&#xD;
      in patients with AF. Investigators will systematically assess prospectively collected CT scan&#xD;
      images for evidence of HT and re-infarction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Hypothesis:&#xD;
&#xD;
      Investigators hypothesize that early initiation of apixaban within the first 14 days of&#xD;
      stroke or TIA is not associated with increased symptomatic intracranial haemorrhage.&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
      EASSE is an investigator-initiated prospective, open label, single arm phase IV study.&#xD;
      Consecutive patients with AF (new onset or previous history) with acute ischemic stroke or&#xD;
      TIA will be screened from Emergency Department or stroke unit. A total of 100 patients will&#xD;
      be recruited within 24 hours of initiation of apixaban after TIA or stroke. All study&#xD;
      participants will be followed for 90 days after apixaban initiation. A National Institute of&#xD;
      Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS), and Montreal Cognitive&#xD;
      Assessment (MoCA) will be collected at baseline, 7, and 90 days after enrolment. All patients&#xD;
      will have a non-contrast CT scan at baseline (within 24 hours from study recruitment) and at&#xD;
      7±2 days after enrolment. In the event of clinical deterioration, a repeat CT scan will be&#xD;
      performed immediately.&#xD;
&#xD;
      Administrative Structure:&#xD;
&#xD;
      Case report forms and data monitoring will be completed on site. All imaging data will be&#xD;
      read centrally at the Stroke Imaging Laboratory at the University of Alberta.&#xD;
&#xD;
      Procedures:&#xD;
&#xD;
      Apixaban therapy: The apixaban dose will be determined by the treating physician, based on&#xD;
      age, weight and renal function as per the product monograph. Patients with two of the&#xD;
      following: Age &gt; 80, weight &lt; 60 kg, and creatinine ≥ 133 (1.5 mg/dl), will have received 2.5&#xD;
      mg twice a day. All other patients will have received 5 mg twice a day.&#xD;
&#xD;
      Imaging Procedures and Analysis:&#xD;
&#xD;
      Anonymized dicom CT data will be analyzed centrally. Baseline infarct volumes will be&#xD;
      measured using planimetric techniques and recurrent infarctions will be identified. Any HT&#xD;
      seen at baseline and day 7 will be graded using European Cooperative Acute Stroke Study&#xD;
      (ECASS) criteria.&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
      The primary endpoint is the symptomatic HT, defined as PH2 associated with a ≥4-point&#xD;
      increase in NIHSS score within 90 days of initiating apixaban therapy. Secondary outcomes&#xD;
      include any HT at day 7, systemic hemorrhagic complications, and recurrent ischemic events&#xD;
      within 90 days of enrolment. Investigators will report serious adverse events (SAE) within&#xD;
      the study period using standardized event, resolution and association codes, and they will be&#xD;
      reported to the local Human Research Ethics Board.&#xD;
&#xD;
      Sample Size:&#xD;
&#xD;
      A sample of 100 patients is planned in order to obtain estimates of the frequency of&#xD;
      symptomatic and asymptomatic HT associated with early apixaban initiation. The maximum&#xD;
      acceptable rate of symptomatic HT is considered 2%, based on a meta-analysis of low molecular&#xD;
      weight heparin treatment in acute stroke, indicating the absolute symptomatic HT rate ranged&#xD;
      from 2.4% to 2.9%.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">September 9, 2019</completion_date>
  <primary_completion_date type="Actual">September 9, 2019</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>90 Days</target_duration>
  <primary_outcome>
    <measure>symptomatic HT</measure>
    <time_frame>90 days</time_frame>
    <description>Defined as PH2 associated with a ≥4-point increase in NIHSS score within 90 days of initiating apixaban therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HT</measure>
    <time_frame>Day 7</time_frame>
    <description>Symptomatic or asymptomatic</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic hemorrhagic complications</measure>
    <time_frame>90 days</time_frame>
    <description>Systemic bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrent ischemic events</measure>
    <time_frame>90 days</time_frame>
    <description>TIA, ischemic stroke, or systemic emboli</description>
  </secondary_outcome>
  <enrollment type="Actual">100</enrollment>
  <condition>Ischemic Stroke</condition>
  <condition>Transient Ischemic Attack</condition>
  <condition>Atrial Fibrillation</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban</intervention_name>
    <description>The decision to treat with apixaban and the timing of initiation will be at the attending physicians' discretion, independent of enrolment in EASSE.</description>
    <other_name>Eliquis</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with ischemic stroke (regardless of the size and severity ) or TIA in patients ≥&#xD;
        18 years of age, with atrial fibrillation (newly or previously diagnosed), who can be&#xD;
        treated with apixaban following stroke.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients&#xD;
&#xD;
          2. Must be ≥ 18 years of age.&#xD;
&#xD;
          3. Diagnosis of ischemic stroke, or Transient Ischemic Attack (TIA, defined as acute&#xD;
             focal neurological deficits, with complete resolution of symptoms within 24 h of&#xD;
             onset). In cases where onset time cannot be established, it will be considered to be&#xD;
             the time when patient was last known to be well.&#xD;
&#xD;
          4. CT scan or MRI, with findings consistent with an ischemic etiology of symptoms.&#xD;
&#xD;
          5. Atrial Fibrillation (AF, paroxysmal or persistent), confirmed with ECG/Holter monitor,&#xD;
             or by history (clinical documentation of previous AF must be provided).&#xD;
&#xD;
          6. Patients prescribed apixaban by their treating physician following their stroke/TIA.&#xD;
&#xD;
          7. Ability to obtain consent from patient or legally authorized representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute or chronic renal failure, defined as eGFR &lt;30 ml/min (Cockcroft Gault formula).&#xD;
&#xD;
          2. Known hypersensitivity to apixaban.&#xD;
&#xD;
          3. Prior treatment with apixaban or any other novel oral anticoagulant (including all&#xD;
             Factor Xa antagonists). Treatment with warfarin prior to the stroke/TIA is acceptable,&#xD;
             but enrolment cannot begin until the INR is ≤2.0.&#xD;
&#xD;
          4. Any significant ongoing systemic bleeding risk, i.e. active GI/GU bleeding or recent&#xD;
             major surgery.&#xD;
&#xD;
          5. Any condition that, in the judgment of the investigator could impose hazards to the&#xD;
             patient if study therapy is initiated or affect the participation of the patient in&#xD;
             the study.&#xD;
&#xD;
          6. Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH),&#xD;
             arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm.&#xD;
&#xD;
          7. Hereditary or acquired haemorrhagic diathesis.&#xD;
&#xD;
          8. Stroke mimics (such as seizures, migraine etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>June 17, 2020</last_update_submitted>
  <last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alberta</investigator_affiliation>
    <investigator_full_name>Ken Butcher</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Atrial fibrillation</keyword>
  <keyword>Ischemic stroke</keyword>
  <keyword>Hemorrhagic transformation</keyword>
  <keyword>Apixaban</keyword>
  <keyword>Cardioembolic stroke</keyword>
  <keyword>Intracerebral hemorrhage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Ischemic Attack, Transient</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apixaban</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 30, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT04435418/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04435418
org study id: Version 1.0 September 30, 2016
nct id: NCT04435418
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Study Design:

      This is an investigator-initiated prospective, open label, single arm phase IV study.
      Patients with documented non-valvular atrial fibrillation (AF) with acute TIA (defined as
      acute focal neurological deficits, with complete resolution of symptoms within 24 h of onset)
      or ischemic stroke, irrespective of infarct volume or clinical severity will be enrolled.

      Study Aim and Objectives:

      The overall aim of this study is to demonstrate the feasibility and safety of initiating
      apixaban therapy within 14 days of TIA or ischemic stroke regardless of the size and severity
      in patients with AF. Investigators will systematically assess prospectively collected CT scan
      images for evidence of HT and re-infarction.
Study Hypothesis:

      Investigators hypothesize that early initiation of apixaban within the first 14 days of
      stroke or TIA is not associated with increased symptomatic intracranial haemorrhage.

      Study Design:

      EASSE is an investigator-initiated prospective, open label, single arm phase IV study.
      Consecutive patients with AF (new onset or previous history) with acute ischemic stroke or
      TIA will be screened from Emergency Department or stroke unit. A total of 100 patients will
      be recruited within 24 hours of initiation of apixaban after TIA or stroke. All study
      participants will be followed for 90 days after apixaban initiation. A National Institute of
      Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS), and Montreal Cognitive
      Assessment (MoCA) will be collected at baseline, 7, and 90 days after enrolment. All patients
      will have a non-contrast CT scan at baseline (within 24 hours from study recruitment) and at
      7±2 days after enrolment. In the event of clinical deterioration, a repeat CT scan will be
      performed immediately.

      Administrative Structure:

      Case report forms and data monitoring will be completed on site. All imaging data will be
      read centrally at the Stroke Imaging Laboratory at the University of Alberta.

      Procedures:

      Apixaban therapy: The apixaban dose will be determined by the treating physician, based on
      age, weight and renal function as per the product monograph. Patients with two of the
      following: Age > 80, weight < 60 kg, and creatinine ≥ 133 (1.5 mg/dl), will have received 2.5
      mg twice a day. All other patients will have received 5 mg twice a day.

      Imaging Procedures and Analysis:

      Anonymized dicom CT data will be analyzed centrally. Baseline infarct volumes will be
      measured using planimetric techniques and recurrent infarctions will be identified. Any HT
      seen at baseline and day 7 will be graded using European Cooperative Acute Stroke Study
      (ECASS) criteria.

      Endpoints:

      The primary endpoint is the symptomatic HT, defined as PH2 associated with a ≥4-point
      increase in NIHSS score within 90 days of initiating apixaban therapy. Secondary outcomes
      include any HT at day 7, systemic hemorrhagic complications, and recurrent ischemic events
      within 90 days of enrolment. Investigators will report serious adverse events (SAE) within
      the study period using standardized event, resolution and association codes, and they will be
      reported to the local Human Research Ethics Board.

      Sample Size:

      A sample of 100 patients is planned in order to obtain estimates of the frequency of
      symptomatic and asymptomatic HT associated with early apixaban initiation. The maximum
      acceptable rate of symptomatic HT is considered 2%, based on a meta-analysis of low molecular
      weight heparin treatment in acute stroke, indicating the absolute symptomatic HT rate ranged
      from 2.4% to 2.9%.
observational model: Cohort
time perspective: Prospective
measure: symptomatic HT
time frame: 90 days
description: Defined as PH2 associated with a ≥4-point increase in NIHSS score within 90 days of initiating apixaban therapy
measure: HT
time frame: Day 7
description: Symptomatic or asymptomatic
measure: Systemic hemorrhagic complications
time frame: 90 days
description: Systemic bleeding
measure: Recurrent ischemic events
time frame: 90 days
description: TIA, ischemic stroke, or systemic emboli
intervention type: Drug
intervention name: Apixaban
description: The decision to treat with apixaban and the timing of initiation will be at the attending physicians' discretion, independent of enrolment in EASSE.
other name: Eliquis
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Alberta
investigator full name: Ken Butcher
investigator title: Professor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Ischemic Attack, Transient
mesh term: Atrial Fibrillation
mesh term: Ischemia
mesh term: Apixaban
provided document: 