<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/NCT01660373</url>
  </required_header>
  <id_info>
    <org_study_id>ISSBRIL0080</org_study_id>
    <nct_id>NCT01660373</nct_id>
  </id_info>
  <brief_title>Comparison of Antiplatelet Effect of Ticagrelor vs Tirofiban in Patients With Non-ST Elevation Acute Coronary Syndrome</brief_title>
  <acronym>TE-CLOT</acronym>
  <official_title>Ticagrelor vs. Tirofiban, Comparison of Anti-platelet Effects in Patients With Non-ST Elevation Acute Coronary Syndrome(TE-CLOT Trial : Ticagrelor's Effect for CLOT Prevention) ; A Single Center, Open-label Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pusan National University Yangsan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Pusan National University Yangsan Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-center, open-label prospective randomized pharmacodynamic investigation of&#xD;
      two anti platelet regimens in patients who are planned to undergo PCI for non-ST segment&#xD;
      elevation acute coronary syndrome(NSTE-ACS) for 24 hours&#xD;
&#xD;
        1. Ticagrelor : loading dose(180mg) followed by maintenance dose(90mg bid)&#xD;
&#xD;
        2. Tirofiban : 0.4ug/kg/min for 30min followed by 0.1ug/kg/min&#xD;
&#xD;
             -  both agents will be given on top of aspirin&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In combination with aspirin, P2Y12 receptor antagonist or glycoprotein IIb/IIIa&#xD;
      inhibitor(GPI) is now a recommended drug as the standard dual antiplatelet regimen in&#xD;
      patients with acute coronary syndrome(1).&#xD;
&#xD;
      Ticagrelor is a newly developed oral P2Y12 receptor inhibitor. It shows faster, greater and&#xD;
      more consistent platelet inhibition as compared with previous P2Y12 receptor antagonist&#xD;
      clopidogrel(2) and it also shows better clinical outcome and similar risk for bleeding as&#xD;
      compared with clopidogrel(3).Interestingly, pharmacodynamic data of some studies showed&#xD;
      excellent effect of ticagrelor in terms of inhibiting platelet activation apparently as high&#xD;
      as that of GPI(2,4).&#xD;
&#xD;
      Primary hypothesis: Ticagrelor have a comparable efficacy in platelet inhibition to GPI in&#xD;
      patients with non-ST segment elevation acute coronary syndrome.&#xD;
&#xD;
      Statistical design : non-inferiority test&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">August 2013</completion_date>
  <primary_completion_date type="Anticipated">August 2013</primary_completion_date>
  <phase>Phase 3</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>Percentage IPA after 20µmol/l ADP at 2 hour</measure>
    <time_frame>2 hours</time_frame>
    <description>Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP and aggregation will be assessed using a light transmittance aggregometer(Chronolog, USA).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen</measure>
    <time_frame>8 hours</time_frame>
    <description>Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen</measure>
    <time_frame>24 hours</time_frame>
    <description>Blood samples with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>periprocedural bleeding</measure>
    <time_frame>0~24 hours</time_frame>
    <description>Periprocedural bleeding will be monitored and described according to BARC and TIMI definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak cardiac enzyme level</measure>
    <time_frame>0~24 hours</time_frame>
    <description>From blood samples at 0, 2H, 8H and 24H, CK-MB and Troponin I will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage IPA after TRAP, arachidonic acid, collagen at 2 hours</measure>
    <time_frame>2 hours</time_frame>
    <description>Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Non-ST Segment Elevation Acute Coronary Syndrome</condition>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>loading dose(180mg) followed by maintenance dose(90mg bid)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tirofiban</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.4ug/kg/min for 30min followed by 0.1ug/kg/min</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tirofiban</intervention_name>
    <description>0.4ug/kg/min for 30min followed by 0.1ug/kg/min</description>
    <arm_group_label>Tirofiban</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor</intervention_name>
    <description>loading dose(180mg) followed by maintenance dose(90mg bid)</description>
    <arm_group_label>Ticagrelor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with recent or current ischemic symptoms at the time of randomization will be&#xD;
             eligible if 2 of the following criteria are met: ST-T change indicating ischemia; a&#xD;
             positive test of biomarker indication myocardial necrosis; or one of several risk&#xD;
             factors(age ≥60 years&#xD;
&#xD;
          -  Previous myocardial infarction or coronary artery bypass grafting [CABG]&#xD;
&#xD;
          -  Coronary artery disease with stenosis of ≥50% in at least two vessels&#xD;
&#xD;
          -  Previous ischemic stroke, transient ischemic attack, carotid stenosis of at least 50%,&#xD;
             or cerebral revascularization&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Peripheral arterial disease; or chronic renal dysfunction, defined as a creatinine&#xD;
             clearance of &lt;60 ml per minute per 1.73 m2 of body surface area)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Administration of fibrinolytic or any GP IIb/IIIa inhibitors for the treatment of&#xD;
             current AMI&#xD;
&#xD;
          2. Major surgery or trauma within 30 days&#xD;
&#xD;
          3. Active bleeding&#xD;
&#xD;
          4. Previous stroke in the last six months&#xD;
&#xD;
          5. Oral anticoagulant therapy&#xD;
&#xD;
          6. Pre-existing thrombocytopenia&#xD;
&#xD;
          7. Vasculitis&#xD;
&#xD;
          8. Hypertensive retinopathy&#xD;
&#xD;
          9. Severe hepatic failure&#xD;
&#xD;
         10. Severe renal failure requiring hemodialysis&#xD;
&#xD;
         11. Documented allergy/intolerance or contraindication to tirofiban or P2Y12 inhibitor&#xD;
&#xD;
         12. Uncontrolled hypertension (systolic or diastolic arterial pressure &gt;180 mmHg or 120,&#xD;
             respectively, despite medical therapy)&#xD;
&#xD;
         13. Limited life expectancy, e.g. neoplasms, others&#xD;
&#xD;
         14. Inability to obtain informed consent&#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>June Hong Kim, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pusan National University Yangsan Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>June Hong Kim, MD,PhD</last_name>
    <phone>+82-10-8231-7171</phone>
    <email>junehongk@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dongcheul Han, MD</last_name>
    <phone>+82-10-2992-6270</phone>
    <email>usdoc12@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Pusan National University Yangsan Hospital</name>
      <address>
        <city>Yangsan</city>
        <state>Kyeongsangnamdo</state>
        <zip>626-770</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>June Hong Kim, MD, PhD</last_name>
      <phone>+82-10-8231-7171</phone>
      <email>junehongk@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Dongcheul Han, MD</last_name>
      <phone>+82-10-2992-6270</phone>
      <email>usdoc12@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>June Hong Kim, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dongcheul Han, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012 Aug 14;60(7):645-81. doi: 10.1016/j.jacc.2012.06.004. Epub 2012 Jul 16. No abstract available.</citation>
    <PMID>22809746</PMID>
  </reference>
  <reference>
    <citation>Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.</citation>
    <PMID>19923168</PMID>
  </reference>
  <reference>
    <citation>Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.</citation>
    <PMID>19717846</PMID>
  </reference>
  <reference>
    <citation>Saltzman AJ, Mehran R, Hooper WC, Moses JW, Weisz G, Collins MB, Lansky AJ, Kreps EM, Leon MB, Stone GW, Dangas G. The relative effects of abciximab and tirofiban on platelet inhibition and C-reactive protein during coronary intervention. J Invasive Cardiol. 2010 Jan;22(1):2-6.</citation>
    <PMID>20048389</PMID>
  </reference>
  <verification_date>December 2012</verification_date>
  <study_first_submitted>August 5, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2012</study_first_posted>
  <last_update_submitted>December 16, 2012</last_update_submitted>
  <last_update_submitted_qc>December 16, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 18, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Pusan National University Yangsan Hospital</investigator_affiliation>
    <investigator_full_name>June Hong Kim</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>ticagrelor</keyword>
  <keyword>tirofiban</keyword>
  <keyword>glycoprotein IIa/IIIa inhibitors</keyword>
  <keyword>P2Y12 blockers</keyword>
  <keyword>acute coronary syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tirofiban</mesh_term>
    <mesh_term>Ticagrelor</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/NCT01660373
org study id: ISSBRIL0080
nct id: NCT01660373
lead sponsor: 
collaborator: 
has dmc: Yes
This is a single-center, open-label prospective randomized pharmacodynamic investigation of
      two anti platelet regimens in patients who are planned to undergo PCI for non-ST segment
      elevation acute coronary syndrome(NSTE-ACS) for 24 hours

        1. Ticagrelor : loading dose(180mg) followed by maintenance dose(90mg bid)

        2. Tirofiban : 0.4ug/kg/min for 30min followed by 0.1ug/kg/min

             -  both agents will be given on top of aspirin
In combination with aspirin, P2Y12 receptor antagonist or glycoprotein IIb/IIIa
      inhibitor(GPI) is now a recommended drug as the standard dual antiplatelet regimen in
      patients with acute coronary syndrome(1).

      Ticagrelor is a newly developed oral P2Y12 receptor inhibitor. It shows faster, greater and
      more consistent platelet inhibition as compared with previous P2Y12 receptor antagonist
      clopidogrel(2) and it also shows better clinical outcome and similar risk for bleeding as
      compared with clopidogrel(3).Interestingly, pharmacodynamic data of some studies showed
      excellent effect of ticagrelor in terms of inhibiting platelet activation apparently as high
      as that of GPI(2,4).

      Primary hypothesis: Ticagrelor have a comparable efficacy in platelet inhibition to GPI in
      patients with non-ST segment elevation acute coronary syndrome.

      Statistical design : non-inferiority test
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage IPA after 20µmol/l ADP at 2 hour
time frame: 2 hours
description: Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP and aggregation will be assessed using a light transmittance aggregometer(Chronolog, USA).
measure: Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen
time frame: 8 hours
description: Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).
measure: Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen
time frame: 24 hours
description: Blood samples with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).
measure: periprocedural bleeding
time frame: 0~24 hours
description: Periprocedural bleeding will be monitored and described according to BARC and TIMI definition
measure: Peak cardiac enzyme level
time frame: 0~24 hours
description: From blood samples at 0, 2H, 8H and 24H, CK-MB and Troponin I will be measured
measure: Percentage IPA after TRAP, arachidonic acid, collagen at 2 hours
time frame: 2 hours
description: Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).
arm group label: Ticagrelor
arm group type: Experimental
description: loading dose(180mg) followed by maintenance dose(90mg bid)
arm group label: Tirofiban
arm group type: Active Comparator
description: 0.4ug/kg/min for 30min followed by 0.1ug/kg/min
intervention type: Drug
intervention name: Tirofiban
description: 0.4ug/kg/min for 30min followed by 0.1ug/kg/min
arm group label: Tirofiban
intervention type: Drug
intervention name: Ticagrelor
description: loading dose(180mg) followed by maintenance dose(90mg bid)
arm group label: Ticagrelor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: June Hong Kim, MD,PhD
role: Principal Investigator
affiliation: Pusan National University Yangsan Hospital
last name: June Hong Kim, MD,PhD
phone: +82-10-8231-7171
email: junehongk@gmail.com
last name: Dongcheul Han, MD
phone: +82-10-2992-6270
email: usdoc12@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Korea, Republic of
citation: Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012 Aug 14;60(7):645-81. doi: 10.1016/j.jacc.2012.06.004. Epub 2012 Jul 16. No abstract available.
PMID: 22809746
citation: Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.
PMID: 19923168
citation: Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.
PMID: 19717846
citation: Saltzman AJ, Mehran R, Hooper WC, Moses JW, Weisz G, Collins MB, Lansky AJ, Kreps EM, Leon MB, Stone GW, Dangas G. The relative effects of abciximab and tirofiban on platelet inhibition and C-reactive protein during coronary intervention. J Invasive Cardiol. 2010 Jan;22(1):2-6.
PMID: 20048389
responsible party type: Principal Investigator
investigator affiliation: Pusan National University Yangsan Hospital
investigator full name: June Hong Kim
investigator title: Professor
mesh term: Acute Coronary Syndrome
mesh term: Syndrome
mesh term: Tirofiban
mesh term: Ticagrelor