<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/NCT02219412</url>
  </required_header>
  <id_info>
    <org_study_id>ISSBRIL0235</org_study_id>
    <nct_id>NCT02219412</nct_id>
  </id_info>
  <brief_title>Arachidonic Acid-induced Platelet Aggregation Rate in Patients With Stable CAD Treated With Ticagrelor Monotherapy</brief_title>
  <official_title>An Open Label, Two Arms, Randomized Controlled Pilot Study Comparing the Arachidonic Acid-induced Platelet Aggregation Rate in Patients With Stable Coronary Artery Disease Treated With Ticagrelor Monotherapy or Ticagrelor and Asprin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yong Huo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University First Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study was a feasibility trial that was designed to provide preliminary observations and&#xD;
      generate hypotheses for future studies. The aim of the study is to estimate the difference of&#xD;
      arachidonic acid induced platelet aggregation rate between ticagrelor mono-therapy and&#xD;
      aspirin/ticagrelor dual-therapy after 14 days of treatment in patients with stable coronary&#xD;
      artery disease. The potential hypothesis is that the arachidonic acid (AA) induced platelet&#xD;
      aggregation rate after 2 weeks of ticagrelor mono-therapy is comparable to that of&#xD;
      aspirin/ticagrelor dual-therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open labeled, active-controlled pilot study to estimate the difference&#xD;
      of arachidonic acid induced platelet aggregation rate between ticagrelor monotherapy and&#xD;
      aspirin/ticagrelor dual-therapy in patients with stable coronary heart disease. The&#xD;
      anticipated duration of the study is approximately 9 months, including an anticipated&#xD;
      enrolment period of 8 months and follow-up period of 4weeks.&#xD;
&#xD;
      Patients with documented coronary heart disease and currently receiving dual-antiplatelet&#xD;
      therapy with standard dose aspirin and clopidogrel will be enrolled from the study site. For&#xD;
      patients post acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI), they&#xD;
      must be on dual-antiplatelet therapy for at least 12 months to be eligible for the study.&#xD;
&#xD;
      The study plan, including enrolment/randomization and follow-up visits, is outlined in Table&#xD;
      1. Eligible patients will enter a washout phase with ticagrelor for 2 weeks. Then they will&#xD;
      be randomized to take either ticagrelor alone or aspirin/ticagrelor for 14 days. The efficacy&#xD;
      evaluation will be done at 7 and 14days after randomization. The primary efficacy parameter&#xD;
      is the rate of arachidonic acid induced platelet aggregation after 14 days of treatment. All&#xD;
      patients will be treated to standards of care for coronary heart disease secondary&#xD;
      prevention.&#xD;
&#xD;
      Visit 0 (Screening and Enrollment, 0 day) All potentially eligible patients will undergo a&#xD;
      screening visit following their signed informed consent.&#xD;
&#xD;
      Following an 8-hour fast, the patients will have screening evaluations performed. Demography,&#xD;
      medical history, and concomitant medication will be recorded. A physical examination and&#xD;
      vital signs(pulse and BP), height and weight, as well as blood sampling for laboratory&#xD;
      assessments of complete blood count (CBC) with differential, serum creatinine, alanine&#xD;
      aminotransferase (ALT) and aspartate aminotransferase (AST), and AA, adenosine diphosphate&#xD;
      (ADP) and collagen induced platelet aggregation rate will be done. Standard 12-lead&#xD;
      electrocardiogram (ECG) readings will be recorded.&#xD;
&#xD;
      Patients meeting all inclusion criteria and with no exclusion criteria will be enrolled.&#xD;
      Patients will receive ticagrelor mono-therapy from the evening for 14 days. IP will be&#xD;
      dispensed.&#xD;
&#xD;
      Visit 1 (Randomization, 14 days) Suspected adverse events (AEs) will be recorded. A physical&#xD;
      examination and vital signs (pulse and BP), as well as blood sampling for laboratory&#xD;
      assessments of AA, ADP and collagen induced platelet aggregation rate and serum thromboxane&#xD;
      B2 concentration will be done.&#xD;
&#xD;
      Patients should be told to take ticagrelor in the morning of Visit 1. Patients will be&#xD;
      randomized in a 1:1 ratio to receive either ticagrelor mono-therapy or aspirin/ticagrelor&#xD;
      dual-therapy. Investigational product (IP) will be returned and compliance assessed and new&#xD;
      bottles of IP will be dispensed according to randomized groups.&#xD;
&#xD;
      Visit 2 (21 days) Suspected AEs will be recorded. Vital signs (pulse and BP) as well as blood&#xD;
      sampling for laboratory assessments of AA, ADP and collagen induced platelet aggregation rate&#xD;
      will be done.&#xD;
&#xD;
      Visit 3 (End of treatment, 28 days) Suspected AEs will be recorded. Vital signs (pulse and&#xD;
      BP) as well as blood sampling for laboratory assessments of CBC with differential, Scr, ALT&#xD;
      and AST, AA, ADP and collagen induced platelet aggregation rate will be done. IP will be&#xD;
      returned and compliance assessed. Instructions for medication after study will be given to&#xD;
      patients at this time.&#xD;
&#xD;
      For patients who prematurely discontinued the randomized treatment, a complete end of&#xD;
      treatment visit will be preferred.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</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>The rate of AA induced platelet aggregation</measure>
    <time_frame>Day 14 after randomization</time_frame>
    <description>The rate of AA induced platelet aggregation will be measured at day 14 after randomization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The rate of ADP induced platelet aggregation</measure>
    <time_frame>Day 7 and day 14 after randomization</time_frame>
    <description>The rate of ADP induced platelet aggregation will be measured at day 7 and day 14 after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The rate of collagen induced platelet aggregation</measure>
    <time_frame>Day 7 and day 14 after randomization</time_frame>
    <description>The rate of d collagen induced platelet aggregation will be measured at day 7 and day 14 after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The serum concentration of Thromboxane B2</measure>
    <time_frame>Day 7 and day 14 after randomization</time_frame>
    <description>The serum concentration of Thromboxane B2 will be measured at day7 and day 14 after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The rate of AA induced platelet aggregation</measure>
    <time_frame>Day 7 after randomization</time_frame>
    <description>The rate of collagen induced platelet aggregation will be measured on Day 7 after randomization</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Coronary Heart Disease</condition>
  <arm_group>
    <arm_group_label>ticagrelor mono-therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Take ticagrelor 90 mg Bid for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>aspirin/ticagrelor dual-therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Take ticagrelor 90mg Bid plus Aspirin 100mg Qd and treated for 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ticagrelor</intervention_name>
    <description>90 mg bid for 2 weeks</description>
    <arm_group_label>aspirin/ticagrelor dual-therapy</arm_group_label>
    <arm_group_label>ticagrelor mono-therapy</arm_group_label>
    <other_name>Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>100mg Qd for 2 weeks.</description>
    <arm_group_label>aspirin/ticagrelor dual-therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of informed consent prior to any study specific procedures.&#xD;
&#xD;
          -  Aged &gt;18 years.&#xD;
&#xD;
          -  Documented stable coronary artery disease.&#xD;
&#xD;
          -  Currently receiving dual-antiplatelet therapy with aspirin 100mg/d and clopidogrel&#xD;
             75mg/d.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of acute coronary syndrome within 12 months of screening.&#xD;
&#xD;
          -  History of percutaneous coronary intervention within 12 months of screening.&#xD;
&#xD;
          -  Any indication (eg, atrial fibrillation,prosthetic heart valve, or coronary stent) for&#xD;
             antithrombotic therapy(eg, warfarin, clopidogrel, or aspirin dose other than 75 to 100&#xD;
             mg/during the study period).&#xD;
&#xD;
          -  AA induced platelet aggregation rate &gt;20% on aspirin+clopidogrel measured by light&#xD;
             transmission platelet aggregation test with the past 3 months.&#xD;
&#xD;
          -  Congestive heart failure or left ventricular ejection fraction &lt;35%.&#xD;
&#xD;
          -  Forced expiratory volume in the first second forced vital capacity below the lower&#xD;
             limits of normal.&#xD;
&#xD;
          -  Bleeding diathesis or severe pulmonary disease.&#xD;
&#xD;
          -  Active pathological bleeding.&#xD;
&#xD;
          -  History of intracranial hemorrhage.&#xD;
&#xD;
          -  Hypersensitivity to ticagrelor or any of the excipients.&#xD;
&#xD;
          -  Severe hepatic impairment.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Current smoking.&#xD;
&#xD;
          -  Platelet count &lt;100 000/mm3 or hemoglobin &lt;10 g/dL.&#xD;
&#xD;
          -  HemoglobinA1c &gt;10%.&#xD;
&#xD;
          -  History of drug addiction or alcohol abuse in the past 2 years.&#xD;
&#xD;
          -  Need for nonsteroidal anti-inflammatory drug.&#xD;
&#xD;
          -  Creatinine clearance&lt;30 mL/min.&#xD;
&#xD;
          -  Concomitant therapy with moderate or strong cytochrome P450 3A inhibitors, substrates,&#xD;
             or strong cytochrome P450 3A inducers.&#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>Huo Yong, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Peking University First Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>June 20, 2016</last_update_submitted>
  <last_update_submitted_qc>June 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 21, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Peking University First Hospital</investigator_affiliation>
    <investigator_full_name>Yong Huo</investigator_full_name>
    <investigator_title>The director of the Department of Cardiology and heart center of Peking University First Hospital</investigator_title>
  </responsible_party>
  <keyword>ticagrelor</keyword>
  <keyword>platelet aggregation rate</keyword>
  <keyword>ADP antagonist</keyword>
  <keyword>antiplatelet therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</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/NCT02219412
org study id: ISSBRIL0235
nct id: NCT02219412
lead sponsor: 
has dmc: No
This study was a feasibility trial that was designed to provide preliminary observations and
      generate hypotheses for future studies. The aim of the study is to estimate the difference of
      arachidonic acid induced platelet aggregation rate between ticagrelor mono-therapy and
      aspirin/ticagrelor dual-therapy after 14 days of treatment in patients with stable coronary
      artery disease. The potential hypothesis is that the arachidonic acid (AA) induced platelet
      aggregation rate after 2 weeks of ticagrelor mono-therapy is comparable to that of
      aspirin/ticagrelor dual-therapy.
This is a randomized, open labeled, active-controlled pilot study to estimate the difference
      of arachidonic acid induced platelet aggregation rate between ticagrelor monotherapy and
      aspirin/ticagrelor dual-therapy in patients with stable coronary heart disease. The
      anticipated duration of the study is approximately 9 months, including an anticipated
      enrolment period of 8 months and follow-up period of 4weeks.

      Patients with documented coronary heart disease and currently receiving dual-antiplatelet
      therapy with standard dose aspirin and clopidogrel will be enrolled from the study site. For
      patients post acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI), they
      must be on dual-antiplatelet therapy for at least 12 months to be eligible for the study.

      The study plan, including enrolment/randomization and follow-up visits, is outlined in Table
      1. Eligible patients will enter a washout phase with ticagrelor for 2 weeks. Then they will
      be randomized to take either ticagrelor alone or aspirin/ticagrelor for 14 days. The efficacy
      evaluation will be done at 7 and 14days after randomization. The primary efficacy parameter
      is the rate of arachidonic acid induced platelet aggregation after 14 days of treatment. All
      patients will be treated to standards of care for coronary heart disease secondary
      prevention.

      Visit 0 (Screening and Enrollment, 0 day) All potentially eligible patients will undergo a
      screening visit following their signed informed consent.

      Following an 8-hour fast, the patients will have screening evaluations performed. Demography,
      medical history, and concomitant medication will be recorded. A physical examination and
      vital signs(pulse and BP), height and weight, as well as blood sampling for laboratory
      assessments of complete blood count (CBC) with differential, serum creatinine, alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST), and AA, adenosine diphosphate
      (ADP) and collagen induced platelet aggregation rate will be done. Standard 12-lead
      electrocardiogram (ECG) readings will be recorded.

      Patients meeting all inclusion criteria and with no exclusion criteria will be enrolled.
      Patients will receive ticagrelor mono-therapy from the evening for 14 days. IP will be
      dispensed.

      Visit 1 (Randomization, 14 days) Suspected adverse events (AEs) will be recorded. A physical
      examination and vital signs (pulse and BP), as well as blood sampling for laboratory
      assessments of AA, ADP and collagen induced platelet aggregation rate and serum thromboxane
      B2 concentration will be done.

      Patients should be told to take ticagrelor in the morning of Visit 1. Patients will be
      randomized in a 1:1 ratio to receive either ticagrelor mono-therapy or aspirin/ticagrelor
      dual-therapy. Investigational product (IP) will be returned and compliance assessed and new
      bottles of IP will be dispensed according to randomized groups.

      Visit 2 (21 days) Suspected AEs will be recorded. Vital signs (pulse and BP) as well as blood
      sampling for laboratory assessments of AA, ADP and collagen induced platelet aggregation rate
      will be done.

      Visit 3 (End of treatment, 28 days) Suspected AEs will be recorded. Vital signs (pulse and
      BP) as well as blood sampling for laboratory assessments of CBC with differential, Scr, ALT
      and AST, AA, ADP and collagen induced platelet aggregation rate will be done. IP will be
      returned and compliance assessed. Instructions for medication after study will be given to
      patients at this time.

      For patients who prematurely discontinued the randomized treatment, a complete end of
      treatment visit will be preferred.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The rate of AA induced platelet aggregation
time frame: Day 14 after randomization
description: The rate of AA induced platelet aggregation will be measured at day 14 after randomization.
measure: The rate of ADP induced platelet aggregation
time frame: Day 7 and day 14 after randomization
description: The rate of ADP induced platelet aggregation will be measured at day 7 and day 14 after randomization.
measure: The rate of collagen induced platelet aggregation
time frame: Day 7 and day 14 after randomization
description: The rate of d collagen induced platelet aggregation will be measured at day 7 and day 14 after randomization.
measure: The serum concentration of Thromboxane B2
time frame: Day 7 and day 14 after randomization
description: The serum concentration of Thromboxane B2 will be measured at day7 and day 14 after randomization
measure: The rate of AA induced platelet aggregation
time frame: Day 7 after randomization
description: The rate of collagen induced platelet aggregation will be measured on Day 7 after randomization
arm group label: ticagrelor mono-therapy
arm group type: Experimental
description: Take ticagrelor 90 mg Bid for 2 weeks.
arm group label: aspirin/ticagrelor dual-therapy
arm group type: Active Comparator
description: Take ticagrelor 90mg Bid plus Aspirin 100mg Qd and treated for 2 weeks.
intervention type: Drug
intervention name: ticagrelor
description: 90 mg bid for 2 weeks
arm group label: aspirin/ticagrelor dual-therapy
arm group label: ticagrelor mono-therapy
other name: Brilinta
intervention type: Drug
intervention name: Aspirin
description: 100mg Qd for 2 weeks.
arm group label: aspirin/ticagrelor dual-therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Huo Yong, MD
role: Study Chair
affiliation: Peking University First Hospital
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Peking University First Hospital
investigator full name: Yong Huo
investigator title: The director of the Department of Cardiology and heart center of Peking University First Hospital
mesh term: Heart Diseases
mesh term: Coronary Disease
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Aspirin
mesh term: Ticagrelor
sharing ipd: No