<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/NCT02215993</url>
  </required_header>
  <id_info>
    <org_study_id>51476</org_study_id>
    <nct_id>NCT02215993</nct_id>
  </id_info>
  <brief_title>Sampling P2Y12 Receptor Inhibition With Prasugrel and Ticagrelor in Patients Submitted to Thrombolysis</brief_title>
  <acronym>SAMPA</acronym>
  <official_title>Sampling P2Y12 Receptor Inhibition With Prasugrel and Ticagrelor in Patients Submitted to Thrombolysis After Loading Dose of Clopidogrel</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal University of São Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federal University of São Paulo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction:&#xD;
&#xD;
      Platelet aggregation plays an important role in ischemic complications in patients undergoing&#xD;
      to percutaneous coronary intervention (PCI). The addition of clopidogrel, as a second&#xD;
      antiplatelet agent, to acetylsalicylic acid (ASA) was effective in reducing major&#xD;
      cardiovascular events in patients with acute coronary syndrome (ACS).&#xD;
&#xD;
      However, approximately 30% of ACS patients are resistant to clopidogrel, representing a&#xD;
      population of medically vulnerable and high risk for major cardiovascular events, including&#xD;
      myocardial infarction (MI), stent thrombosis and death.&#xD;
&#xD;
      In the randomized trial TRITON, prasugrel compared to clopidogrel was more effective in&#xD;
      significantly reducing the rates of MI (7.4% vs. 9.4%) and stent thrombosis (2.4% vs .1,1%)&#xD;
      in patients with ACS, however, patients treated with prasugrel showed higher rates of&#xD;
      bleeding (2.4 vs. 1.8%) and no difference in mortality. Upon analysis of subgroups is not&#xD;
      recommended its use in patients with a history of stroke in those older than 75 years and&#xD;
      weighing less than 60 kg.&#xD;
&#xD;
      The latest class of inhibitors of the P2Y12 receptor is the cyclopentyl-triazolopyrimidines&#xD;
      represented by ticagrelor. Unlike the thienopyridines, ticagrelor interacts with the platelet&#xD;
      receptors in a reversible way and has a beginning and peak of action faster.&#xD;
&#xD;
      The efficacy and safety of ticagrelor were evaluated in the study PLATO, where 18.624&#xD;
      patients with ACS were randomized to receive clopidogrel (75mg/day, with a loading dose of&#xD;
      300 to 600mg) or ticagrelor (90mg 2x/day with a loading dose of 180mg) The primary combined&#xD;
      endpoint (mortality from vascular causes, MI or stroke) at 12 months was significantly lower&#xD;
      in the ticagrelor (9.8% vs. 11.7%). There was no significant difference in the rates of major&#xD;
      bleeding in both groups. Moreover, the isolated analysis of the rates of MI, vascular&#xD;
      mortality and mortality from all causes showed statistically significant reduction in the&#xD;
      ticagrelor users. In this study, the main adverse effects were dyspnea and bradycardia.&#xD;
&#xD;
      The assessment of platelet reactivity may allow the individualization of antiplatelet&#xD;
      therapy. However, simply increasing the dose of clopidogrel in patients who persisted with&#xD;
      high platelet reactivity was not able to reduce the combined endpoint of cardiovascular&#xD;
      death, nonfatal myocardial infarction and stent thrombosis in six months.&#xD;
&#xD;
      In a population of patients with stable coronary artery disease, the substitution of&#xD;
      clopidogrel for ticagrelor showed a rapid and persistent decrease in platelet aggregation&#xD;
      measured by different laboratory methods. However, in patients with ACS subjected to PCI, the&#xD;
      assessment of platelet aggregation after the replacement of clopidogrel for prasugrel or&#xD;
      ticagrelor still requires evidence.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To evaluate the platelet response to ticagrelor and prasugrel in ACS patients with ST-segment&#xD;
      elevation submitted to thrombolysis.&#xD;
&#xD;
      To evaluate security in follow up of 30 days.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      The study will be a prospective, randomized, single-center (São Paulo Hospital - Federal&#xD;
      University of São Paulo), single-blind. The investigators will select 50 patients admitted&#xD;
      with ACS with ST-segment elevation submitted to thrombolysis and who underwent cardiac&#xD;
      catheterization between 3 to 24 hours in the case of reperfusion or immediately for rescue&#xD;
      angioplasty. Blood sample for analysis of platelet aggregation through the system VerifyNow&#xD;
      ®, shall be obtained immediately after the procedure on patients on clopidogrel for at least&#xD;
      seven days in maintenance dose of 75mg or after 8 to 6 hours after the dose of 300mg and&#xD;
      600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose&#xD;
      of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg&#xD;
      and maintained for thirty days at a daily dose of 10mg. A new blood sample and analysis of&#xD;
      platelet aggregation will be repeated after 2, 6 and 24 hours. The demographic and clinical&#xD;
      data of this population will be collected in specific form and stored in databases for later&#xD;
      analysis&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2013</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of change in platelet aggregation</measure>
    <time_frame>time 0, 2, 6 and 24 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of incidence of bleeding</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Acute Coronary Syndrome</condition>
  <condition>Platelet Function</condition>
  <arm_group>
    <arm_group_label>Prasugrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After 300mg or 600mg loading dose of clopidogrel, this medication will be replaced by 60 mg prasugrel followed by 10mg per day for 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After 300mg or 600mg loading dose of clopidogrel, this medication will be replaced by 180 mg ticagrelor followed by 90mg twice a day for 30 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prasugrel</intervention_name>
    <description>After 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg.</description>
    <arm_group_label>Prasugrel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor</intervention_name>
    <description>After 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg.</description>
    <arm_group_label>Ticagrelor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  less than 75 years&#xD;
&#xD;
          -  sign the consent form&#xD;
&#xD;
          -  Acute coronary syndrome with ST-segment elevation submitted to thrombolysis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  use of IIbIIIa inhibitor&#xD;
&#xD;
          -  less than 60 kg&#xD;
&#xD;
          -  history of stroke&#xD;
&#xD;
          -  Patients with sick sinus syndrome, atrioventricular block second or third degree, not&#xD;
             protected by pacemaker&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease&#xD;
&#xD;
          -  Asthma&#xD;
&#xD;
          -  Heart failure class III / IV&#xD;
&#xD;
          -  renal replacement therapy&#xD;
&#xD;
          -  Use of inducers (carbamazepine, phenytoin, phenobarbital, rifampicin and&#xD;
             dexamethasone) or inhibitors (ketoconazole, itraconazole, ritonavir, saquinavir,&#xD;
             clarithromycin) potent enzyme PYP3A&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leonardo Guimaraes</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of São Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adriano Caixeta</last_name>
    <role>Study Director</role>
    <affiliation>Federal University of São Paulo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Federal University of São Paulo</name>
      <address>
        <city>São Paulo</city>
        <zip>04024-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>June 3, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>May 22, 2017</last_update_submitted>
  <last_update_submitted_qc>May 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Federal University of São Paulo</investigator_affiliation>
    <investigator_full_name>Leonardo de Freitas Campos Guimarães</investigator_full_name>
    <investigator_title>PhD student</investigator_title>
  </responsible_party>
  <keyword>Ticagrelor</keyword>
  <keyword>Prasugrel</keyword>
  <keyword>VerifyNow</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ticagrelor</mesh_term>
    <mesh_term>Prasugrel Hydrochloride</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/NCT02215993
org study id: 51476
nct id: NCT02215993
lead sponsor: 
has dmc: No
Introduction:

      Platelet aggregation plays an important role in ischemic complications in patients undergoing
      to percutaneous coronary intervention (PCI). The addition of clopidogrel, as a second
      antiplatelet agent, to acetylsalicylic acid (ASA) was effective in reducing major
      cardiovascular events in patients with acute coronary syndrome (ACS).

      However, approximately 30% of ACS patients are resistant to clopidogrel, representing a
      population of medically vulnerable and high risk for major cardiovascular events, including
      myocardial infarction (MI), stent thrombosis and death.

      In the randomized trial TRITON, prasugrel compared to clopidogrel was more effective in
      significantly reducing the rates of MI (7.4% vs. 9.4%) and stent thrombosis (2.4% vs .1,1%)
      in patients with ACS, however, patients treated with prasugrel showed higher rates of
      bleeding (2.4 vs. 1.8%) and no difference in mortality. Upon analysis of subgroups is not
      recommended its use in patients with a history of stroke in those older than 75 years and
      weighing less than 60 kg.

      The latest class of inhibitors of the P2Y12 receptor is the cyclopentyl-triazolopyrimidines
      represented by ticagrelor. Unlike the thienopyridines, ticagrelor interacts with the platelet
      receptors in a reversible way and has a beginning and peak of action faster.

      The efficacy and safety of ticagrelor were evaluated in the study PLATO, where 18.624
      patients with ACS were randomized to receive clopidogrel (75mg/day, with a loading dose of
      300 to 600mg) or ticagrelor (90mg 2x/day with a loading dose of 180mg) The primary combined
      endpoint (mortality from vascular causes, MI or stroke) at 12 months was significantly lower
      in the ticagrelor (9.8% vs. 11.7%). There was no significant difference in the rates of major
      bleeding in both groups. Moreover, the isolated analysis of the rates of MI, vascular
      mortality and mortality from all causes showed statistically significant reduction in the
      ticagrelor users. In this study, the main adverse effects were dyspnea and bradycardia.

      The assessment of platelet reactivity may allow the individualization of antiplatelet
      therapy. However, simply increasing the dose of clopidogrel in patients who persisted with
      high platelet reactivity was not able to reduce the combined endpoint of cardiovascular
      death, nonfatal myocardial infarction and stent thrombosis in six months.

      In a population of patients with stable coronary artery disease, the substitution of
      clopidogrel for ticagrelor showed a rapid and persistent decrease in platelet aggregation
      measured by different laboratory methods. However, in patients with ACS subjected to PCI, the
      assessment of platelet aggregation after the replacement of clopidogrel for prasugrel or
      ticagrelor still requires evidence.

      Objectives:

      To evaluate the platelet response to ticagrelor and prasugrel in ACS patients with ST-segment
      elevation submitted to thrombolysis.

      To evaluate security in follow up of 30 days.

      Methods:

      The study will be a prospective, randomized, single-center (São Paulo Hospital - Federal
      University of São Paulo), single-blind. The investigators will select 50 patients admitted
      with ACS with ST-segment elevation submitted to thrombolysis and who underwent cardiac
      catheterization between 3 to 24 hours in the case of reperfusion or immediately for rescue
      angioplasty. Blood sample for analysis of platelet aggregation through the system VerifyNow
      ®, shall be obtained immediately after the procedure on patients on clopidogrel for at least
      seven days in maintenance dose of 75mg or after 8 to 6 hours after the dose of 300mg and
      600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose
      of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg
      and maintained for thirty days at a daily dose of 10mg. A new blood sample and analysis of
      platelet aggregation will be repeated after 2, 6 and 24 hours. The demographic and clinical
      data of this population will be collected in specific form and stored in databases for later
      analysis
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Assessment of change in platelet aggregation
time frame: time 0, 2, 6 and 24 hours
measure: The number of incidence of bleeding
time frame: 30 days
arm group label: Prasugrel
arm group type: Active Comparator
description: After 300mg or 600mg loading dose of clopidogrel, this medication will be replaced by 60 mg prasugrel followed by 10mg per day for 30 days.
arm group label: Ticagrelor
arm group type: Active Comparator
description: After 300mg or 600mg loading dose of clopidogrel, this medication will be replaced by 180 mg ticagrelor followed by 90mg twice a day for 30 days.
intervention type: Drug
intervention name: Prasugrel
description: After 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg.
arm group label: Prasugrel
intervention type: Drug
intervention name: Ticagrelor
description: After 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg.
arm group label: Ticagrelor
criteria: 
gender: All
minimum age: N/A
maximum age: 75 Years
healthy volunteers: No
last name: Leonardo Guimaraes
role: Principal Investigator
affiliation: Federal University of São Paulo
last name: Adriano Caixeta
role: Study Director
affiliation: Federal University of São Paulo
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Federal University of São Paulo
investigator full name: Leonardo de Freitas Campos Guimarães
investigator title: PhD student
mesh term: Acute Coronary Syndrome
mesh term: Ticagrelor
mesh term: Prasugrel Hydrochloride