<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/NCT02206815</url>
  </required_header>
  <id_info>
    <org_study_id>ISSBRIL0256</org_study_id>
    <nct_id>NCT02206815</nct_id>
  </id_info>
  <brief_title>Safety of &quot;Ticagrelor+ Warfarin&quot;in Comparison With &quot;Clopidogrel+Aspirin+Warfarin&quot;</brief_title>
  <official_title>Safety of Ticagrelor Plus Warfarin Versus Clopidogrel+Aspirin+Warfarin in Patients With Persistent or Permanent Atrial Fibrillation and Undergoing PCI-S: A Randomized, Open, Controlled, Parallel Group, Multi-center Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genshan Ma</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zhongda Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Southeast University, China</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study was to assess safety of antithrombotic drug ticagrelor plus oral&#xD;
      anticoagulation adopted in persistent or permanent AF(Atrial fibrillation)&#xD;
      patients（CHA2DS2VASc≥2） after PCI-S with specially regard to the occurrence of major bleeding&#xD;
      complications. We hypothesized that baseline characteristics (ie age, anemia, previous major&#xD;
      bleeding) and type of antithrombotic regimen could influence any bleeding events and the time&#xD;
      of bleeding occurrence. We will test this hypothesis by comparing those AF patients who&#xD;
      subsequently received double antithrombotic therapy (Ticagrelor + Warfarin) vs. triple&#xD;
      antithrombotic therapy (Clopidogrel + Aspirin + Warfarin) after undergoing PCI-S.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently, the optimal antithrombotic treatment of AF patients with indication for long-term&#xD;
      oral anticoagulation undergoing PCI-S is unknown. The randomized trials to assess the best&#xD;
      antithrombotic regimen in this setting and the management of this population are challenging.&#xD;
      It poses imperative demands for future prospective randomized studies to define the optimal&#xD;
      antithrombotic regimen in patients requiring chronic anticoagulation undergoing coronary&#xD;
      stenting. Additionally, the vast majority of current clinical studies about antithrombotic&#xD;
      therapy for atrial fibrillation together with PCI were retrospectively analysis to date&#xD;
      ,whereas the prospective studies are rare and urgently needed&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 19, 2014</start_date>
  <completion_date type="Actual">February 20, 2019</completion_date>
  <primary_completion_date type="Actual">February 20, 2019</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>Overall bleeding events</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Major bleeding events</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">296</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Ticagrelor+Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ticagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clopidogrel+Aspirin+Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clopidogrel:Light red bisulfate tablets, containing one 75mg; Aspirin:Plain, round, white, film-coated tablet, 100mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor+Warfarin</intervention_name>
    <description>Ticagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5)</description>
    <arm_group_label>Ticagrelor+Warfarin</arm_group_label>
    <other_name>Double antithrombotic therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel+Aspirin+Warfarin</intervention_name>
    <description>Clopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5)</description>
    <arm_group_label>Clopidogrel+Aspirin+Warfarin</arm_group_label>
    <other_name>Triple antithrombotic therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Volunteered to participate in this study and signed an informed consent form;&#xD;
&#xD;
          -  Men or non-pregnant women ≥ 18 and ≤75 years of age;&#xD;
&#xD;
          -  Lesion is located in a coronary artery and the need for coronary drug-eluting stent&#xD;
             implantation;&#xD;
&#xD;
          -  Patients with persistent or permanent atrial fibrillation;&#xD;
&#xD;
          -  Score of CHA2DS2VASc≥2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe liver and kidney diseases (GFR&lt;60 ml/min/1.73m2 or CTP≥6 score);&#xD;
&#xD;
          -  Moderate to severe hypertension (after standard antihypertensive therapy, blood&#xD;
             pressure higher than 160/100mmHg);&#xD;
&#xD;
          -  Patients with hemodynamic or electrical instability (including shock);&#xD;
&#xD;
          -  Coagulation disorders associated with significant bleeding tendency (eg,&#xD;
             hypersensitivity, active bleeding, moderate or severe liver disease, history of&#xD;
             previous intracranial bleed, GI bleed within the past 6 months, major surgery within&#xD;
             30 days);&#xD;
&#xD;
          -  Patients with ischemic stroke within one week;&#xD;
&#xD;
          -  Patients with Bronchial asthma, Chronic obstructive pulmonary disease (COPD), and&#xD;
             patients with diseases related to dyspnoea;&#xD;
&#xD;
          -  Any contraindication against the use of ticagrelor and other study drugs;&#xD;
&#xD;
          -  Platelet count less than 100 x 109/L;&#xD;
&#xD;
          -  Haemoglobin (Hb) level less than 100 g/L;&#xD;
&#xD;
          -  Researchers involved in the study and / or immediate family members;&#xD;
&#xD;
          -  Participation in another investigation drug or device study in the past 30 days before&#xD;
             enrollment;&#xD;
&#xD;
          -  Involvement in the planning and conduct of the study (applies to staffs at study&#xD;
             sites);&#xD;
&#xD;
          -  Suffering from other serious disorders and the life expectancy less than half year;&#xD;
&#xD;
          -  Increased risk of bradycardic events (e.g. no pacemaker and known sick sinus syndrome,&#xD;
             second degree A-V block, third degree A-V block or previous documented syncope&#xD;
             suspected to be due to bradycardia). The Sponsor will review the Holter data in this&#xD;
             study to assess the need to continue with this exclusion;&#xD;
&#xD;
          -  Pregnancy or lactation or females of child-bearing potential with the plan of&#xD;
             pregnancy in one year;&#xD;
&#xD;
          -  Concomitant oral or intravenous therapy (see examples below) with strong CYP3A&#xD;
             inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers&#xD;
             which cannot be stopped for the course of the study （Strong inhibitors: ketoconazole,&#xD;
             itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir,&#xD;
             saquinavir, nelfinavir, indinavir, atanazavir; Substrates with narrow therapeutic&#xD;
             index: cyclosporine, quinidine；Strong inducers: rifampin/rifampicin, phenytoin,&#xD;
             carbamazepine).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Genshan Ma, PhD.</last_name>
    <role>Study Director</role>
    <affiliation>Southeast University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yu Wang, MD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southeast University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yuyu Yao, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southeast University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Wenbin Lu, MD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southeast University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cong Fu, MD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southeast University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>LIjuan Chen, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southeast University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zhongda Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The forth hospital of Xuzhou</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <zip>0516</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangbin hospital</name>
      <address>
        <city>Zhenjiang</city>
        <state>Jiangsu</state>
        <zip>0511</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Southeast University, China</investigator_affiliation>
    <investigator_full_name>Genshan Ma</investigator_full_name>
    <investigator_title>Genshan Ma, MD, PhD, Director of Cardiovascular Institute, Southeast University</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
    <mesh_term>Ticagrelor</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/NCT02206815
org study id: ISSBRIL0256
nct id: NCT02206815
lead sponsor: 
collaborator: 
has dmc: Yes
The aim of this study was to assess safety of antithrombotic drug ticagrelor plus oral
      anticoagulation adopted in persistent or permanent AF(Atrial fibrillation)
      patients（CHA2DS2VASc≥2） after PCI-S with specially regard to the occurrence of major bleeding
      complications. We hypothesized that baseline characteristics (ie age, anemia, previous major
      bleeding) and type of antithrombotic regimen could influence any bleeding events and the time
      of bleeding occurrence. We will test this hypothesis by comparing those AF patients who
      subsequently received double antithrombotic therapy (Ticagrelor + Warfarin) vs. triple
      antithrombotic therapy (Clopidogrel + Aspirin + Warfarin) after undergoing PCI-S.
Currently, the optimal antithrombotic treatment of AF patients with indication for long-term
      oral anticoagulation undergoing PCI-S is unknown. The randomized trials to assess the best
      antithrombotic regimen in this setting and the management of this population are challenging.
      It poses imperative demands for future prospective randomized studies to define the optimal
      antithrombotic regimen in patients requiring chronic anticoagulation undergoing coronary
      stenting. Additionally, the vast majority of current clinical studies about antithrombotic
      therapy for atrial fibrillation together with PCI were retrospectively analysis to date
      ,whereas the prospective studies are rare and urgently needed
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall bleeding events
time frame: 18 months
measure: Major bleeding events
time frame: 18 months
arm group label: Ticagrelor+Warfarin
arm group type: Active Comparator
description: Ticagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg
arm group label: Clopidogrel+Aspirin+Warfarin
arm group type: Active Comparator
description: Clopidogrel:Light red bisulfate tablets, containing one 75mg; Aspirin:Plain, round, white, film-coated tablet, 100mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg
intervention type: Drug
intervention name: Ticagrelor+Warfarin
description: Ticagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5)
arm group label: Ticagrelor+Warfarin
other name: Double antithrombotic therapy
intervention type: Drug
intervention name: Clopidogrel+Aspirin+Warfarin
description: Clopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5)
arm group label: Clopidogrel+Aspirin+Warfarin
other name: Triple antithrombotic therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Genshan Ma, PhD.
role: Study Director
affiliation: Southeast University
last name: Yu Wang, MD.
role: Principal Investigator
affiliation: Southeast University
last name: Yuyu Yao, Ph.D
role: Principal Investigator
affiliation: Southeast University
last name: Wenbin Lu, MD.
role: Principal Investigator
affiliation: Southeast University
last name: Cong Fu, MD.
role: Principal Investigator
affiliation: Southeast University
last name: LIjuan Chen, PhD.
role: Principal Investigator
affiliation: Southeast University
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Southeast University, China
investigator full name: Genshan Ma
investigator title: Genshan Ma, MD, PhD, Director of Cardiovascular Institute, Southeast University
mesh term: Atrial Fibrillation
mesh term: Coronary Artery Disease
mesh term: Aspirin
mesh term: Warfarin
mesh term: Clopidogrel
mesh term: Ticagrelor
sharing ipd: No