<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/NCT01706510</url>
  </required_header>
  <id_info>
    <org_study_id>ISSBRIL0076</org_study_id>
    <nct_id>NCT01706510</nct_id>
  </id_info>
  <brief_title>Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients</brief_title>
  <official_title>A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rapid City Regional Hospital, Inc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Rapid City Regional Hospital, Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assess the pharmacodynamic effect of ticagrelor vs. Clopidogrel in American Indian patients&#xD;
      with stable coronary artery disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet&#xD;
      Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary&#xD;
      Artery Disease&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">March 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Compare ticagrelor's versus clopidogrel's inhibition of the P2Y12 receptor as measured by the decrease in P2Y12 Reaction Units (PRU) using VerifyNow TM.</measure>
    <time_frame>At 2 hour time point after loading dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the decrease of P2Y12 Reaction Units (PRU) by VerifyNow TM from ticagrelor and clopidogrel.</measure>
    <time_frame>0.5 and 8 hour time points after loading dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the decrease in P2Y l2 Reaction Units (PRU) by VerifyNow™ from ticagrelor's and clopidogrel's morning dose on Day 7</measure>
    <time_frame>At the 2, 8, and 24 hours after the last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate and compare the pharmacodynamic effects, measured by the vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index [PRI]), in all subjects</measure>
    <time_frame>Day1: pre-dose, 0.5, 2, and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours post final dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess and to compare the percentage of subjects with High on-treatment Platelet Reactivity (HPR) at all time points after randomized study treatment.</measure>
    <time_frame>Day 1: Pre-dose, 0.5, 2 and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours after final dose</time_frame>
    <description>The High on-treatment Platelet Reactivity will be defined in accordance with the following platelet inhibition level cut-off.&#xD;
&gt; 208 PRU by the VerifyNow P2Y12 assay&#xD;
&gt; 230 PRU by the VerifyNow P2Y12 assay&#xD;
&gt; 50% PRI by the VASP assay</description>
  </secondary_outcome>
  <other_outcome>
    <measure>CYP2C19 genotyping to identifying the wild-type CYP2C19 allele (*1), and characterize common alleles known to effect the metabolism of clopidogrel (*2, *3, *4,*5,*6,*7,*8 responsible for poor metabolism and *17 allele responsible for rapid metabolism).</measure>
    <time_frame>One time-point</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clopidogrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clopidogrel 600 mg Loading Dose followed by 75 mg Daily for 7 days ± 2 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor</intervention_name>
    <description>Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days</description>
    <arm_group_label>Clopidogrel</arm_group_label>
    <arm_group_label>Ticagrelor</arm_group_label>
    <other_name>Brand Name: Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <description>Clopidogrel 600 mg loading dose followed by 75 mg Daily for 7 days ± 2 days</description>
    <arm_group_label>Clopidogrel</arm_group_label>
    <arm_group_label>Ticagrelor</arm_group_label>
    <other_name>Brand Name: Plavix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented stable CAD fulfilling any of the following, and taking 81mg ASA daily&#xD;
             treatment:&#xD;
&#xD;
          -  Females must be post menopausal for at least one year or surgically sterile for at&#xD;
             least 6 months and negative urine pregnancy test&#xD;
&#xD;
          -  Self-identified as American Indian&#xD;
&#xD;
          -  Genetic Inclusion Criteria: must sign the informed consent for genetic and biological&#xD;
             sample banking.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any indication for oral anticoagulant or dual antiplatelet treatment&#xD;
&#xD;
          -  Concomitant therapy with strong CYP3A inhibitors, CYP3A substrates with narrow&#xD;
             therapeutic index, or strong CYP3A inducers within 14 days and during study treatment&#xD;
             and during:&#xD;
&#xD;
          -  Increased bleeding risk including:&#xD;
&#xD;
          -  Diabetic patients with HbAlC &gt; 10% at screening&#xD;
&#xD;
          -  Contraindication to clopidogrel, ASA, or ticagrelor - A history of alcohol and/or&#xD;
             substance abuse that could interfere with conduct of the trial&#xD;
&#xD;
          -  Patients requiring dialysis&#xD;
&#xD;
          -  Patients scheduled for revascularization (e.g., PCI, CABG) during the study period&#xD;
&#xD;
          -  Any acute or chronic unstable condition in the past 30 days&#xD;
&#xD;
          -  Known active or recurrent hepatic disorder&#xD;
&#xD;
          -  Patients who had ACS or stent placed within 12 months of screening&#xD;
&#xD;
          -  History of Uric Acid nephropathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James S Walder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rapid City Regional Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Regional Heart Doctors/Black Hills Cardiovascular Research</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <last_update_submitted>May 4, 2015</last_update_submitted>
  <last_update_submitted_qc>May 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 5, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clopidogrel</keyword>
  <keyword>Ticagrelor</keyword>
  <keyword>Coronary Artery Disease</keyword>
  <keyword>Myocardial Ischemia</keyword>
  <keyword>Coronary Disease</keyword>
  <keyword>Heart Diseases</keyword>
  <keyword>Cardiovascular Diseases</keyword>
  <keyword>Arteriosclerosis</keyword>
  <keyword>Arterial Occlusive Diseases</keyword>
  <keyword>Vascular Diseases</keyword>
  <keyword>Platelet Aggregation Inhibitors</keyword>
  <keyword>Hematologic Agents</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Purinergic P2Y Receptor Antagonists</keyword>
  <keyword>Purinergic P2 Receptor Antagonists</keyword>
  <keyword>Purinergic Antagonists</keyword>
  <keyword>Purinergic Agents</keyword>
  <keyword>Physiological Effects of Drugs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clopidogrel</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/NCT01706510
org study id: ISSBRIL0076
nct id: NCT01706510
lead sponsor: 
collaborator: 
has dmc: No
Assess the pharmacodynamic effect of ticagrelor vs. Clopidogrel in American Indian patients
      with stable coronary artery disease.
A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet
      Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary
      Artery Disease
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Compare ticagrelor's versus clopidogrel's inhibition of the P2Y12 receptor as measured by the decrease in P2Y12 Reaction Units (PRU) using VerifyNow TM.
time frame: At 2 hour time point after loading dose
measure: Compare the decrease of P2Y12 Reaction Units (PRU) by VerifyNow TM from ticagrelor and clopidogrel.
time frame: 0.5 and 8 hour time points after loading dose
measure: Compare the decrease in P2Y l2 Reaction Units (PRU) by VerifyNow™ from ticagrelor's and clopidogrel's morning dose on Day 7
time frame: At the 2, 8, and 24 hours after the last dose
measure: To evaluate and compare the pharmacodynamic effects, measured by the vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index [PRI]), in all subjects
time frame: Day1: pre-dose, 0.5, 2, and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours post final dose
measure: Assess and to compare the percentage of subjects with High on-treatment Platelet Reactivity (HPR) at all time points after randomized study treatment.
time frame: Day 1: Pre-dose, 0.5, 2 and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours after final dose
description: The High on-treatment Platelet Reactivity will be defined in accordance with the following platelet inhibition level cut-off.
> 208 PRU by the VerifyNow P2Y12 assay
> 230 PRU by the VerifyNow P2Y12 assay
> 50% PRI by the VASP assay
measure: CYP2C19 genotyping to identifying the wild-type CYP2C19 allele (*1), and characterize common alleles known to effect the metabolism of clopidogrel (*2, *3, *4,*5,*6,*7,*8 responsible for poor metabolism and *17 allele responsible for rapid metabolism).
time frame: One time-point
arm group label: Ticagrelor
arm group type: Experimental
description: Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days
arm group label: Clopidogrel
arm group type: Active Comparator
description: Clopidogrel 600 mg Loading Dose followed by 75 mg Daily for 7 days ± 2 days
intervention type: Drug
intervention name: Ticagrelor
description: Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days
arm group label: Clopidogrel
arm group label: Ticagrelor
other name: Brand Name: Brilinta
intervention type: Drug
intervention name: Clopidogrel
description: Clopidogrel 600 mg loading dose followed by 75 mg Daily for 7 days ± 2 days
arm group label: Clopidogrel
arm group label: Ticagrelor
other name: Brand Name: Plavix
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James S Walder, MD
role: Principal Investigator
affiliation: Rapid City Regional Hospital
facility: 
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Clopidogrel
mesh term: Ticagrelor