<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/NCT02998905</url>
  </required_header>
  <id_info>
    <org_study_id>NASPAF-ICH</org_study_id>
    <nct_id>NCT02998905</nct_id>
  </id_info>
  <brief_title>NOACs for Stroke Prevention in Patients With Atrial Fibrillation and Previous ICH</brief_title>
  <acronym>NASPAF-ICH</acronym>
  <official_title>Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation and Previous Intracerebral Hemorrhage Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Population Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Population Health Research Institute</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>
      To determine the feasibility of a controlled trial examining the efficacy and safety of&#xD;
      non-vitamin K antagonist oral anticoagulants (NOACs) compared with ASA for stroke prevention&#xD;
      in patients with a high-risk of atrial fibrillation and previous intracerebral hemorrhage.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The NASPAF-ICH study is an open-label, randomized, controlled, phase II study that will&#xD;
      assess the feasibility of a controlled trial examining the efficacy and safety of non-vitamin&#xD;
      K antagonist oral anticoagulants (NOACs) compared with acetylsalicylic acid (ASA) for stroke&#xD;
      prevention in patients with high-risk atrial fibrillation and previous intracerebral&#xD;
      hemorrhage, as well as provide evidence of efficacy and safety for planning of a phase III&#xD;
      trial. Recruitment will occur at 10 high-volume stroke research centres across Canada over 2&#xD;
      years, at which 100 adult patients with high-risk atrial fibrillation (CHADS2 ≥2) and&#xD;
      previous spontaneous or traumatic ICH (intraparenchymal or intraventricular hemorrhage while&#xD;
      on or off anticoagulation) will be randomly assigned to receive a NOAC (particular agent at&#xD;
      the discretion of the local investigator) or ASA 81 mg per day. Patients will be followed for&#xD;
      a mean of 1 year to a common end-study date. The feasibility of recruitment will also be&#xD;
      tested. The investigators estimate that five patients per year per centre can be recruited.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 26, 2017</start_date>
  <completion_date type="Actual">February 18, 2020</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Phase 2</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recruitment rate</measure>
    <time_frame>Through study completion; ~ 30 months</time_frame>
    <description>The mean number of patients randomized per site per year.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite of ischemic stroke and recurrent intracerebral hemorrhage</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>The composite of ischemic stroke and recurrent intracerebral hemorrhage</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Refusal rate</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Average number of eligible patients per site who refuse consent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retention rate</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Randomized patients who completed 6 months of follow-up on drug or died during trial participation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ischemic stroke</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracerebral hemorrhage</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>A neurologic deficit associated with an intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatal stroke</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Death that is attributable to an ischemic stroke or intracerebral hemorrhage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial infarction</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Defined by presence of at least one of the following a compatible clinical history and characteristic serum enzymes changes with or without electrocardiographic abnormalities; clinical history and serial ST-segment and T-wave changes which are specifically located with respect to the electrocardiographic leads accompanied by elevation of CPK-MB isoenzyme or troponin in serum; the development of large Q-waves on electrocardiography associated with changes in the ST-segments and T-waves in specific and appropriate leads which indicate the location of the infarct, even in the absence of symptoms or abnormalities in serum enzymes; development of discrete, segmental left ventricular systolic wall motion abnormality concurrent with compatible clinical history, electrocardiographic changes or serum enzyme abnormalities; or histopathological evidence of subacute myocardial necrosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Persistent and irreversible absence of brain or brainstem function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic thromboembolism</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major hemorrhage</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Bleeding accompanied by one or more of the following - a decrease in the hemoglobin level of ≥20 g per liter over a 24-hour period, transfusion of ≥2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial hemorrhage</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of all stroke, myocardial infarct, systemic thromboembolism or death</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Composite of all stroke, myocardial infarct, systemic thromboembolism or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale (mRS)</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Average mRS score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Montreal Cognitive Assessment (MOCA)</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Average MOCA score</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Weighted net clinical benefit</measure>
    <time_frame>Through study completion; average of 1 year</time_frame>
    <description>Weighted net clinical benefit factoring the impact of ischemic stroke, intracerebral hemorrhage, non-intracerebral intracranial hemorrhage, major extracranial hemorrhage and myocardial infarction on death and disability.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Intracerebral Hemorrhage</condition>
  <arm_group>
    <arm_group_label>NOAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apixaban or dabigatran or edoxaban or rivaroxaban</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acetylsalicylic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Acetylsalicylic acid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NOAC</intervention_name>
    <description>Apixaban or dabigatran or edoxaban or rivaroxaban at recommended dosing for stroke prevention in atrial fibrillation. The particular agent is at the discretion of the local investigator.</description>
    <arm_group_label>NOAC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetylsalicylic Acid</intervention_name>
    <description>Acetylsalicylic acid 81 mg/day</description>
    <arm_group_label>Acetylsalicylic Acid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previous primary intracerebral hemorrhage&#xD;
&#xD;
          -  Atrial fibrillation (CHADS2 ≥ 2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-stroke indication for antiplatelet or anticoagulant therapy&#xD;
&#xD;
          -  Recent intracerebral hemorrhage within 14 days&#xD;
&#xD;
          -  Platelet count less than 100,000/mm3 at enrollment or other bleeding diathesis&#xD;
&#xD;
          -  Prior symptomatic lobar intracerebral hemorrhage other than the qualifying event&#xD;
&#xD;
          -  Uncontrollable hypertension consistently above SBP/DBP of 160/100 mmHg&#xD;
&#xD;
          -  Known hypersensitivity to either ASA or NOACs&#xD;
&#xD;
          -  Inability to adhere to study procedures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ashkan Shoamanesh, MD FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Population Health Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver Coastal Health Research Institute</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6T 2B5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L9G1J8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre - University Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Western Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Notre-Dame du CHUM</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 25, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>March 18, 2020</last_update_submitted>
  <last_update_submitted_qc>March 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Population Health Research Institute</investigator_affiliation>
    <investigator_full_name>Ashkan Shoamanesh</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine (Neurology)</investigator_title>
  </responsible_party>
  <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>Aspirin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02998905
org study id: NASPAF-ICH
nct id: NCT02998905
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To determine the feasibility of a controlled trial examining the efficacy and safety of
      non-vitamin K antagonist oral anticoagulants (NOACs) compared with ASA for stroke prevention
      in patients with a high-risk of atrial fibrillation and previous intracerebral hemorrhage.
The NASPAF-ICH study is an open-label, randomized, controlled, phase II study that will
      assess the feasibility of a controlled trial examining the efficacy and safety of non-vitamin
      K antagonist oral anticoagulants (NOACs) compared with acetylsalicylic acid (ASA) for stroke
      prevention in patients with high-risk atrial fibrillation and previous intracerebral
      hemorrhage, as well as provide evidence of efficacy and safety for planning of a phase III
      trial. Recruitment will occur at 10 high-volume stroke research centres across Canada over 2
      years, at which 100 adult patients with high-risk atrial fibrillation (CHADS2 ≥2) and
      previous spontaneous or traumatic ICH (intraparenchymal or intraventricular hemorrhage while
      on or off anticoagulation) will be randomly assigned to receive a NOAC (particular agent at
      the discretion of the local investigator) or ASA 81 mg per day. Patients will be followed for
      a mean of 1 year to a common end-study date. The feasibility of recruitment will also be
      tested. The investigators estimate that five patients per year per centre can be recruited.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Recruitment rate
time frame: Through study completion; ~ 30 months
description: The mean number of patients randomized per site per year.
measure: Composite of ischemic stroke and recurrent intracerebral hemorrhage
time frame: Through study completion; average of 1 year
description: The composite of ischemic stroke and recurrent intracerebral hemorrhage
measure: Refusal rate
time frame: Through study completion; average of 1 year
description: Average number of eligible patients per site who refuse consent.
measure: Retention rate
time frame: Through study completion; average of 1 year
description: Randomized patients who completed 6 months of follow-up on drug or died during trial participation.
measure: Ischemic stroke
time frame: Through study completion; average of 1 year
description: Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.
measure: Intracerebral hemorrhage
time frame: Through study completion; average of 1 year
description: A neurologic deficit associated with an intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.
measure: Fatal stroke
time frame: Through study completion; average of 1 year
description: Death that is attributable to an ischemic stroke or intracerebral hemorrhage.
measure: Myocardial infarction
time frame: Through study completion; average of 1 year
description: Defined by presence of at least one of the following a compatible clinical history and characteristic serum enzymes changes with or without electrocardiographic abnormalities; clinical history and serial ST-segment and T-wave changes which are specifically located with respect to the electrocardiographic leads accompanied by elevation of CPK-MB isoenzyme or troponin in serum; the development of large Q-waves on electrocardiography associated with changes in the ST-segments and T-waves in specific and appropriate leads which indicate the location of the infarct, even in the absence of symptoms or abnormalities in serum enzymes; development of discrete, segmental left ventricular systolic wall motion abnormality concurrent with compatible clinical history, electrocardiographic changes or serum enzyme abnormalities; or histopathological evidence of subacute myocardial necrosis.
measure: All-cause mortality
time frame: Through study completion; average of 1 year
description: Persistent and irreversible absence of brain or brainstem function.
measure: Systemic thromboembolism
time frame: Through study completion; average of 1 year
description: Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage.
measure: Major hemorrhage
time frame: Through study completion; average of 1 year
description: Bleeding accompanied by one or more of the following - a decrease in the hemoglobin level of ≥20 g per liter over a 24-hour period, transfusion of ≥2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding.
measure: Intracranial hemorrhage
time frame: Through study completion; average of 1 year
description: Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.
measure: Composite of all stroke, myocardial infarct, systemic thromboembolism or death
time frame: Through study completion; average of 1 year
description: Composite of all stroke, myocardial infarct, systemic thromboembolism or death
measure: Modified Rankin Scale (mRS)
time frame: Through study completion; average of 1 year
description: Average mRS score
measure: Montreal Cognitive Assessment (MOCA)
time frame: Through study completion; average of 1 year
description: Average MOCA score
measure: Weighted net clinical benefit
time frame: Through study completion; average of 1 year
description: Weighted net clinical benefit factoring the impact of ischemic stroke, intracerebral hemorrhage, non-intracerebral intracranial hemorrhage, major extracranial hemorrhage and myocardial infarction on death and disability.
arm group label: NOAC
arm group type: Experimental
description: Apixaban or dabigatran or edoxaban or rivaroxaban
arm group label: Acetylsalicylic Acid
arm group type: Active Comparator
description: Acetylsalicylic acid
intervention type: Drug
intervention name: NOAC
description: Apixaban or dabigatran or edoxaban or rivaroxaban at recommended dosing for stroke prevention in atrial fibrillation. The particular agent is at the discretion of the local investigator.
arm group label: NOAC
intervention type: Drug
intervention name: Acetylsalicylic Acid
description: Acetylsalicylic acid 81 mg/day
arm group label: Acetylsalicylic Acid
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Ashkan Shoamanesh, MD FRCPC
role: Principal Investigator
affiliation: Population Health Research Institute
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Population Health Research Institute
investigator full name: Ashkan Shoamanesh
investigator title: Assistant Professor of Medicine (Neurology)
mesh term: Cerebral Hemorrhage
mesh term: Atrial Fibrillation
mesh term: Hemorrhage
mesh term: Aspirin
sharing ipd: No