<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/NCT02224131</url>
  </required_header>
  <id_info>
    <org_study_id>BT-1401</org_study_id>
    <nct_id>NCT02224131</nct_id>
  </id_info>
  <brief_title>Study of Antiplatelet Therapy for Intracranial Aneurysm Stent-assisted Coiling</brief_title>
  <acronym>ATIASC</acronym>
  <official_title>Randomized Comparison of Platelet Function Monitoring to Adjust Antiplatelet Therapy Versus a Common Antiplatelet Treatment for Intracranial Aneurysm Stent-assisted Coiling</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Tiantan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Tiantan Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring&#xD;
      offers the opportunity to improve outcomes of intracranial aneurysm patients undergoing stent&#xD;
      deployment by individualizing therapy.This trial is designed to demonstrate the superiority&#xD;
      of a strategy of platelet function monitoring with dose adjustment in suboptimal responders&#xD;
      as compared to a more conventional strategy without monitoring and without dose adjustment to&#xD;
      reduce the primary end point evaluated 6 months after stent deployment in patients with&#xD;
      intracranial aneurysms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participating Centers : 10 China high neurointervention volume (&gt;200) centers Rationale:&#xD;
      Clopidogrel (75 mg/day), in combination with aspirin (100 mg/day), is currently the&#xD;
      antiplatelet treatment of choice for prevention of stent thrombosis, and clinical trials have&#xD;
      shown that, in high-risk patients, prolonged dual antiplatelet treatment is more effective&#xD;
      than aspirin alone in preventing major thromboembolic events. However, despite the use of&#xD;
      clopidogrel, a considerable number of patients continue to have thromboembolic events.&#xD;
      Numerous in VITRO studies have shown that individual responsiveness to clopidogrel but also&#xD;
      to aspirin is not uniform in all patients and is subject to inter- and intraindividual&#xD;
      variability. The recent possibility of bedside monitoring of oral antiplatelet therapy offers&#xD;
      the unique opportunity of tailoring antiplatelet therapy. However, the relevance of such&#xD;
      strategy has never been evaluated in a randomized prospective adequately powered study of&#xD;
      intracranial aneurysm patients. Late state stent thrombosis and after interruption of OAT, is&#xD;
      another important safety issue raising the questions of the modalities of interruption of&#xD;
      dual OAT within six months according to the most recent updated recommendations. When is the&#xD;
      best interruption of dual OAT? Our first hypothesis is that a strategy of dose adjustment of&#xD;
      OAT based on biological monitoring reduces the rate of the combined ischemic endpoints of&#xD;
      death, stent thrombosis and stroke as compared to a conventional strategy (local practice&#xD;
      without monitoring) in patients scheduled for intracranial stent implantation and followed up&#xD;
      for six months. Our second hypothesis is that interruption of clopidogrel after 1.5 months of&#xD;
      dual OAT is associated with a higher rate of the same combined ischemic endpoints as compared&#xD;
      with patients in whom dual OAT is maintained for 3 months follow-up.&#xD;
&#xD;
      Objectives: 1) To demonstrate the superiority of the strategy of monitoring with dose&#xD;
      adjustment in suboptimal responders (Monitoring Arm) as compared to a more conventional&#xD;
      strategy (Conventional Arm) with fixed dose regimen of both oral antiplatelet agents in all&#xD;
      patients as defined by the international guidelines to reduce the primary endpoint evaluated&#xD;
      one year after DES implantation. 2) to demonstrate the superiority of a strategy of pursuit&#xD;
      of a dual OAT beyond 3 months(Pursuit Arm) as compared to a strategy of interruption for 1.5&#xD;
      months(Interruption Arm).&#xD;
&#xD;
      Duration of the participation : from 18 up to 30 months according to the time delay from&#xD;
      study start to randomization. No participants will be excluded from the study at the&#xD;
      exception of consent withdrawal. However, participants who have not been randomized for&#xD;
      interruption or continuation of DAPT at the 6 month follow up visit will terminate the study&#xD;
&#xD;
      Number of patients: 1856 patients. This number was obtained for the demonstration of the&#xD;
      superiority of the strategy of monitoring (Monitoring Arm) over the conventional strategy&#xD;
      (Conventional Arm) to reduce the primary endpoint by 33% (relative risk reduction).&#xD;
&#xD;
      Expected results: The ARCTIC study will provide answers to two major clinical challenges. It&#xD;
      will also give a unique opportunity to assess the prevalence and the associated risk factors&#xD;
      of suboptimal answers to OAT, but also to improve a suboptimal biological response. Finally,&#xD;
      the economic impact of both strategies of monitoring and of interruption will be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2015</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">June 2020</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ischemia stroke</measure>
    <time_frame>within 6 months after the stent placement</time_frame>
    <description>Evidence of clinically definite ischemic stroke confirmed by MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>bleeding</measure>
    <time_frame>within 6 months after stent placement</time_frame>
    <description>Evidence of clinically definite bleeding complication confirmed by CT or clinical symptoms</description>
  </secondary_outcome>
  <other_outcome>
    <measure>recurrence of aneurysm, all causes of death</measure>
    <time_frame>within 6 months after stent placement</time_frame>
    <description>Evidence of clinically definite recurrence of aneurysm confirmed by DSA</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1856</enrollment>
  <condition>Embolic Stroke</condition>
  <arm_group>
    <arm_group_label>Monitoring Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dose adjustment of both aspirin and clopidogrel in suboptimal responders identified based on a point of care assay(TEG)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>fixed dose regiment of both aspirin and clopidogrel in all patients following stent deployment according to international guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin and clopidogrel</intervention_name>
    <description>modification of aspirin and clopidogrelmaintenance doses based on a biological assay Device:thrombelastography(TEG) point of care assay TEG(Haemoscope Corporation, Niles, IL)</description>
    <arm_group_label>Conventional Arm</arm_group_label>
    <arm_group_label>Monitoring Arm</arm_group_label>
    <other_name>Aspirin Enteric Coated Tablets ,Bayer HealthCare AG ;</other_name>
    <other_name>Plavix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin and clopidogrel</intervention_name>
    <description>aspirin and clopidogrel maintenance doses (according to international guidelines)</description>
    <arm_group_label>Conventional Arm</arm_group_label>
    <arm_group_label>Monitoring Arm</arm_group_label>
    <other_name>Aspirin Enteric Coated Tablets</other_name>
    <other_name>Plavix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients (≥18 years) in whom elective intracranial stent placement is scheduled after&#xD;
             diagnostic angiography&#xD;
&#xD;
          -  Patients not treated by GPIIb/IIIa inhibitors prior to randomization.&#xD;
&#xD;
          -  Provided written consent for participation in the trial prior to any study-specific&#xD;
             procedures or requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  •Oral anticoagulation (Vitamin K Antagonists).&#xD;
&#xD;
               -  Contraindication for aspirin and/or clopidogrel or GPIIb/IIIa inhibitors or to&#xD;
                  increasing dose of clopidogrel or aspirin&#xD;
&#xD;
               -  Ongoing or recent bleeding and/or recent major surgery (&lt;3 weeks)&#xD;
&#xD;
               -  Severe liver dysfunction&#xD;
&#xD;
               -  Thrombocytopenia (Platelet count &lt;80000/µl).&#xD;
&#xD;
               -  IIb/IIIa inhibitors within a week prior to randomization&#xD;
&#xD;
               -  multiple intracranial aneurysms&#xD;
&#xD;
               -  Patient at risk of poor compliance to the study&#xD;
&#xD;
               -  Patient not affiliated to social security&#xD;
&#xD;
               -  Pregnant women, no signed inform consent&#xD;
&#xD;
               -  Any invasive or surgical planned intervention during the year after stent&#xD;
                  placement&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Youxiang Li, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Department of neurointervention of Beijing Neurosurgical Institute,capital medical university ,China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hongchao Yang, Doctor</last_name>
    <phone>+86010-67098847</phone>
    <email>yhchao2007@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Tiantan Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100050</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Youxiang Li, Doctor</last_name>
      <phone>86010_67098847</phone>
      <email>yhchao2007@163.com</email>
    </contact>
    <investigator>
      <last_name>Hongchao Yang, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Collet JP, Cuisset T, Range G, Cayla G, Elhadad S, Pouillot C, Henry P, Motreff P, Carrie D, Boueri Z, Belle L, Van Belle E, Rousseau H, Aubry P, Monsegu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Barthelemy O, Beygui F, Silvain J, Vicaut E, Montalescot G; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012 Nov 29;367(22):2100-9. doi: 10.1056/NEJMoa1209979. Epub 2012 Nov 4.</citation>
    <PMID>23121439</PMID>
  </reference>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <last_update_submitted>August 22, 2014</last_update_submitted>
  <last_update_submitted_qc>August 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Tiantan Hospital</investigator_affiliation>
    <investigator_full_name>Youxiang Li</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>platelet function test</keyword>
  <keyword>stent;</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intracranial Aneurysm</mesh_term>
    <mesh_term>Embolic Stroke</mesh_term>
    <mesh_term>Aneurysm</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Clopidogrel</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/NCT02224131
org study id: BT-1401
nct id: NCT02224131
lead sponsor: 
has dmc: Yes
Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring
      offers the opportunity to improve outcomes of intracranial aneurysm patients undergoing stent
      deployment by individualizing therapy.This trial is designed to demonstrate the superiority
      of a strategy of platelet function monitoring with dose adjustment in suboptimal responders
      as compared to a more conventional strategy without monitoring and without dose adjustment to
      reduce the primary end point evaluated 6 months after stent deployment in patients with
      intracranial aneurysms.
Participating Centers : 10 China high neurointervention volume (>200) centers Rationale:
      Clopidogrel (75 mg/day), in combination with aspirin (100 mg/day), is currently the
      antiplatelet treatment of choice for prevention of stent thrombosis, and clinical trials have
      shown that, in high-risk patients, prolonged dual antiplatelet treatment is more effective
      than aspirin alone in preventing major thromboembolic events. However, despite the use of
      clopidogrel, a considerable number of patients continue to have thromboembolic events.
      Numerous in VITRO studies have shown that individual responsiveness to clopidogrel but also
      to aspirin is not uniform in all patients and is subject to inter- and intraindividual
      variability. The recent possibility of bedside monitoring of oral antiplatelet therapy offers
      the unique opportunity of tailoring antiplatelet therapy. However, the relevance of such
      strategy has never been evaluated in a randomized prospective adequately powered study of
      intracranial aneurysm patients. Late state stent thrombosis and after interruption of OAT, is
      another important safety issue raising the questions of the modalities of interruption of
      dual OAT within six months according to the most recent updated recommendations. When is the
      best interruption of dual OAT? Our first hypothesis is that a strategy of dose adjustment of
      OAT based on biological monitoring reduces the rate of the combined ischemic endpoints of
      death, stent thrombosis and stroke as compared to a conventional strategy (local practice
      without monitoring) in patients scheduled for intracranial stent implantation and followed up
      for six months. Our second hypothesis is that interruption of clopidogrel after 1.5 months of
      dual OAT is associated with a higher rate of the same combined ischemic endpoints as compared
      with patients in whom dual OAT is maintained for 3 months follow-up.

      Objectives: 1) To demonstrate the superiority of the strategy of monitoring with dose
      adjustment in suboptimal responders (Monitoring Arm) as compared to a more conventional
      strategy (Conventional Arm) with fixed dose regimen of both oral antiplatelet agents in all
      patients as defined by the international guidelines to reduce the primary endpoint evaluated
      one year after DES implantation. 2) to demonstrate the superiority of a strategy of pursuit
      of a dual OAT beyond 3 months(Pursuit Arm) as compared to a strategy of interruption for 1.5
      months(Interruption Arm).

      Duration of the participation : from 18 up to 30 months according to the time delay from
      study start to randomization. No participants will be excluded from the study at the
      exception of consent withdrawal. However, participants who have not been randomized for
      interruption or continuation of DAPT at the 6 month follow up visit will terminate the study

      Number of patients: 1856 patients. This number was obtained for the demonstration of the
      superiority of the strategy of monitoring (Monitoring Arm) over the conventional strategy
      (Conventional Arm) to reduce the primary endpoint by 33% (relative risk reduction).

      Expected results: The ARCTIC study will provide answers to two major clinical challenges. It
      will also give a unique opportunity to assess the prevalence and the associated risk factors
      of suboptimal answers to OAT, but also to improve a suboptimal biological response. Finally,
      the economic impact of both strategies of monitoring and of interruption will be evaluated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: ischemia stroke
time frame: within 6 months after the stent placement
description: Evidence of clinically definite ischemic stroke confirmed by MRI
measure: bleeding
time frame: within 6 months after stent placement
description: Evidence of clinically definite bleeding complication confirmed by CT or clinical symptoms
measure: recurrence of aneurysm, all causes of death
time frame: within 6 months after stent placement
description: Evidence of clinically definite recurrence of aneurysm confirmed by DSA
arm group label: Monitoring Arm
arm group type: Experimental
description: dose adjustment of both aspirin and clopidogrel in suboptimal responders identified based on a point of care assay(TEG)
arm group label: Conventional Arm
arm group type: Active Comparator
description: fixed dose regiment of both aspirin and clopidogrel in all patients following stent deployment according to international guidelines
intervention type: Drug
intervention name: Aspirin and clopidogrel
description: modification of aspirin and clopidogrelmaintenance doses based on a biological assay Device:thrombelastography(TEG) point of care assay TEG(Haemoscope Corporation, Niles, IL)
arm group label: Conventional Arm
arm group label: Monitoring Arm
other name: Aspirin Enteric Coated Tablets ,Bayer HealthCare AG ;
other name: Plavix
intervention type: Drug
intervention name: Aspirin and clopidogrel
description: aspirin and clopidogrel maintenance doses (according to international guidelines)
arm group label: Conventional Arm
arm group label: Monitoring Arm
other name: Aspirin Enteric Coated Tablets
other name: Plavix
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Youxiang Li, Professor
role: Study Chair
affiliation: Department of neurointervention of Beijing Neurosurgical Institute,capital medical university ,China
last name: Hongchao Yang, Doctor
phone: +86010-67098847
email: yhchao2007@163.com
facility: 
contact: 
investigator: 
country: China
citation: Collet JP, Cuisset T, Range G, Cayla G, Elhadad S, Pouillot C, Henry P, Motreff P, Carrie D, Boueri Z, Belle L, Van Belle E, Rousseau H, Aubry P, Monsegu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Barthelemy O, Beygui F, Silvain J, Vicaut E, Montalescot G; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012 Nov 29;367(22):2100-9. doi: 10.1056/NEJMoa1209979. Epub 2012 Nov 4.
PMID: 23121439
responsible party type: Principal Investigator
investigator affiliation: Beijing Tiantan Hospital
investigator full name: Youxiang Li
investigator title: Professor
mesh term: Intracranial Aneurysm
mesh term: Embolic Stroke
mesh term: Aneurysm
mesh term: Aspirin
mesh term: Clopidogrel