<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/NCT02201394</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 13-1802</org_study_id>
    <nct_id>NCT02201394</nct_id>
  </id_info>
  <brief_title>Reversing Ticagrelor's Effects With Fresh Platelets</brief_title>
  <official_title>Normalizing Platelet Reactivity After Treatment With Ticagrelor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary&#xD;
      artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to&#xD;
      wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to&#xD;
      shorten this period could be useful. The present study aims to investigate the possibility of&#xD;
      reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets.&#xD;
      Fresh platelets will be added to blood samples of treated patients in varying concentrations&#xD;
      at specific timepoints to determine the time and amount of fresh platelets needed to&#xD;
      normalize platelet reactivity in the treated samples.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines&#xD;
      for ACS patients requiring CABG surgery after treatment with dual antiplatelet therapy&#xD;
      recommend delaying surgery for 5-7 days after discontinuation of therapy, to allow for the&#xD;
      dissipation of its antiplatelet effects. This treatment-devoid waiting period puts the ACS&#xD;
      patients at risk for further cardiovascular events. Any means to shorten this vulnerable&#xD;
      period would be of critical value. One possibility to speed up the recovery of the inhibited&#xD;
      platelets is to administer infusions of fresh platelets. In fact, platelet transfusions are&#xD;
      frequently administered to patients during surgery who had received prior antiplatelet&#xD;
      therapy. However, the degree to which these transfusions restore platelet function in the&#xD;
      recipient subjects' blood and the time from dosing when they are most effective are unknown.&#xD;
      The timing is critical in scenarios where urgent surgery is required because infusion of&#xD;
      platelets too soon after antiplatelet dosing could render them useless by the residual drug&#xD;
      in circulation.&#xD;
&#xD;
      The aim of the present study is to investigate the restoration of platelet function of&#xD;
      ticagrelor-treated subjects by adding donor platelets to their blood. The study would have 2&#xD;
      arms mimicking different clinical scenarios:&#xD;
&#xD;
        1. Clinical Scenario 1 - Patient given a loading dose (LD) of ticagrelor in the emergency&#xD;
           room, requires surgery: A single LD of ticagrelor (180 mg) with aspirin (325 mg) will be&#xD;
           given to study subjects and platelet testing will be performed after addition of fresh&#xD;
           platelets to their blood ex vivo. Donor platelets will be added at 4-, 6-, 24- and&#xD;
           48-hours post-dose, to assess the time required for normalizing subject's platelet&#xD;
           function after a LD of ticagrelor.&#xD;
&#xD;
        2. Clinical Scenario 2 - Patient on maintenance dosing (MD) of ticagrelor, requires&#xD;
           surgery: Subjects will receive ticagrelor (90 mg twice daily) with aspirin (81 mg once&#xD;
           daily) for 3-7 days. After the last dose, platelet testing will be performed after&#xD;
           addition of fresh platelets to their blood ex vivo, at 4-, 6-, 24- and 48-hours&#xD;
           post-dose to assess the time required for normalizing subject's platelet function after&#xD;
           daily treatment with ticagrelor.&#xD;
&#xD;
      Platelet testing will be carried out using the following methodologies:&#xD;
&#xD;
        1. Platelet Aggregation - VerifyNow P2Y12 assay.&#xD;
&#xD;
        2. Platelet Aggregation - Multiplate Analyzer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>P2Y12 Reaction Unit (PRU)</measure>
    <time_frame>Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose</time_frame>
    <description>Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Platelet Aggregation Using Multiplate Analyzer</measure>
    <time_frame>Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose</time_frame>
    <description>Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Loading dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor loading dose</intervention_name>
    <description>Single loading dose of Ticagrelor 180 mg</description>
    <arm_group_label>Loading dose</arm_group_label>
    <other_name>Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin loading dose</intervention_name>
    <description>Single loading dose of Aspirin 325 mg</description>
    <arm_group_label>Loading dose</arm_group_label>
    <other_name>Acetylsalicylic acid</other_name>
    <other_name>ASA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor maintenance dose</intervention_name>
    <description>Ticagrelor 90 mg twice daily x 7 days</description>
    <arm_group_label>Maintenance dose</arm_group_label>
    <other_name>Ticagrelor</other_name>
    <other_name>Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin maintenance dose</intervention_name>
    <description>Aspirin 81 mg once daily x 7 days</description>
    <arm_group_label>Maintenance dose</arm_group_label>
    <other_name>Aspirin</other_name>
    <other_name>ASA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female volunteer between 18 and 75 years old.&#xD;
&#xD;
          -  History of stable (i.e. non-acute) cardiovascular disease or the presence of risk&#xD;
             factors for cardiovascular disease (i.e. hypertension, diabetes, hyperlipidemia, high&#xD;
             calcium score and abnormal findings on angiography or stress test).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Conditions associated with hemorrhagic risk, e.g., frequent epistaxis,&#xD;
             gastrointestinal ulcer, hemorrhagic vascular lesions, recent surgery.&#xD;
&#xD;
          -  Allergy or hypersensitivity to aspirin or ticagrelor.&#xD;
&#xD;
          -  Loss of &gt;400 mL blood or blood donation within past 3 months.&#xD;
&#xD;
          -  Positive serology for hepatitis B (HBs Ag) or hepatitis C.&#xD;
&#xD;
          -  History of drug abuse or alcohol abuse.&#xD;
&#xD;
          -  Positive pregnancy test.&#xD;
&#xD;
          -  Evidence of unstable or acute cardiovascular disease (e.g., unstable angina, recent&#xD;
             myocardial infarction, congestive heart failure).&#xD;
&#xD;
          -  History of clinically relevant pulmonary, hepatic, gastrointestinal, renal, metabolic,&#xD;
             hematologic, neurologic, respiratory or psychiatric disease, bleeding, acute&#xD;
             infectious disease or signs of acute illness.&#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>Juan J Badimon, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <results_first_submitted>September 26, 2017</results_first_submitted>
  <results_first_submitted_qc>October 31, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 5, 2017</results_first_posted>
  <last_update_submitted>October 31, 2017</last_update_submitted>
  <last_update_submitted_qc>October 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Juan J Badimon</investigator_full_name>
    <investigator_title>Director, AtheroThrombosis Research Unit; Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Antiplatelet</keyword>
  <keyword>Ticagrelor</keyword>
  <keyword>Platelets</keyword>
  <keyword>Thrombosis</keyword>
  <keyword>Coronary artery disease</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>Aspirin</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Patients With Stable CVD</title>
          <description>DAPT loading dose (Ticagrelor (180 mg) + ASA (325 mg)); DAPT maintenance therapy (Ticagrelor (90 mg BID) + ASA (81 mg OD), for one week (in same patients)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Loading Dose</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Maintenance Dose</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Patients With Stable CVD</title>
          <description>DAPT loading dose (Ticagrelor (180 mg) + ASA (325 mg)); DAPT maintenance therapy (Ticagrelor (90 mg BID) + ASA (81 mg OD), for one week (in same patients)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.9" spread="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetic</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <description>Body Mass Index</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.7" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hypertension</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic blood pressure</title>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="127.2" spread="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic blood pressure</title>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.6" spread="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hypercholesterolemia</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cholesterol level</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="158.7" spread="62.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Triglycerides level</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="165.4" spread="91.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LDL level</title>
          <description>low-density lipoprotein</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85.6" spread="51.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HDL</title>
          <description>high-density lipoprotein</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42.5" spread="12.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking History</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Current</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Past</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Never</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alcohol Use</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Current</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Past</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Never</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>P2Y12 Reaction Unit (PRU)</title>
        <description>Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.</description>
        <time_frame>Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose</time_frame>
        <population>Patients with stable CVD</population>
        <group_list>
          <group group_id="O1">
            <title>Loading Dose</title>
            <description>Ticagrelor (180 mg) + ASA (325 mg).</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Dose</title>
            <description>Ticagrelor (90 mg BID) + ASA (81 mg OD), for one week</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Unit (PRU)</title>
          <description>Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.</description>
          <population>Patients with stable CVD</population>
          <units>PRU</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="284.1" spread="42.2"/>
                    <measurement group_id="O2" value="284.1" spread="42.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 4 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.1" spread="25.9"/>
                    <measurement group_id="O2" value="37.5" spread="32.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.6" spread="35.6"/>
                    <measurement group_id="O2" value="72.2" spread="38.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.3" spread="49.6"/>
                    <measurement group_id="O2" value="88.4" spread="42.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.6" spread="54.4"/>
                    <measurement group_id="O2" value="85.9" spread="49.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 6 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.9" spread="28.9"/>
                    <measurement group_id="O2" value="24.0" spread="30.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.3" spread="50.2"/>
                    <measurement group_id="O2" value="46.0" spread="37.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.8" spread="53.8"/>
                    <measurement group_id="O2" value="55.4" spread="41.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.2" spread="42.8"/>
                    <measurement group_id="O2" value="67.7" spread="45.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 24 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="127.6" spread="58.8"/>
                    <measurement group_id="O2" value="119.0" spread="78.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="157.3" spread="52.5"/>
                    <measurement group_id="O2" value="147.6" spread="65.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.9" spread="40.5"/>
                    <measurement group_id="O2" value="158.0" spread="43.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="162.5" spread="29.4"/>
                    <measurement group_id="O2" value="154.0" spread="51.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 48 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="250.6" spread="45.8"/>
                    <measurement group_id="O2" value="214.8" spread="74.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="249.5" spread="35.1"/>
                    <measurement group_id="O2" value="219.7" spread="52.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="226.2" spread="51.6"/>
                    <measurement group_id="O2" value="221.2" spread="44.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="204.2" spread="45.9"/>
                    <measurement group_id="O2" value="203.9" spread="41.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Platelet Aggregation Using Multiplate Analyzer</title>
        <description>Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.</description>
        <time_frame>Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose</time_frame>
        <population>Patients with stable CVD</population>
        <group_list>
          <group group_id="O1">
            <title>Loading Dose</title>
            <description>Ticagrelor (180 mg) + ASA (325 mg).</description>
          </group>
          <group group_id="O2">
            <title>Maintenance Dose</title>
            <description>Ticagrelor (90 mg BID) + ASA (81 mg OD), for one week</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Aggregation Using Multiplate Analyzer</title>
          <description>Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.</description>
          <population>Patients with stable CVD</population>
          <units>10 AU * min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (pre-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.0" spread="14.3"/>
                    <measurement group_id="O2" value="67.0" spread="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 4 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6" spread="4.6"/>
                    <measurement group_id="O2" value="15.7" spread="6.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.7" spread="5.2"/>
                    <measurement group_id="O2" value="20.9" spread="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.4" spread="7.7"/>
                    <measurement group_id="O2" value="22.1" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.6" spread="8.4"/>
                    <measurement group_id="O2" value="24.2" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 6 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" spread="5.9"/>
                    <measurement group_id="O2" value="13.4" spread="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.3" spread="6.1"/>
                    <measurement group_id="O2" value="16.5" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.7" spread="6.5"/>
                    <measurement group_id="O2" value="18.9" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.3" spread="7.5"/>
                    <measurement group_id="O2" value="20.4" spread="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post dose 24 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.9" spread="14.0"/>
                    <measurement group_id="O2" value="25.6" spread="15.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.7" spread="18.1"/>
                    <measurement group_id="O2" value="35.5" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.3" spread="17.9"/>
                    <measurement group_id="O2" value="43.3" spread="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.8" spread="22.7"/>
                    <measurement group_id="O2" value="47.5" spread="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-dose 48 hours 0%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.3" spread="17.7"/>
                    <measurement group_id="O2" value="39.1" spread="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours 25%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.7" spread="17.6"/>
                    <measurement group_id="O2" value="56.8" spread="19.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours 50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.6" spread="20.4"/>
                    <measurement group_id="O2" value="63.8" spread="19.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours 75%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.8" spread="18.4"/>
                    <measurement group_id="O2" value="70.3" spread="23.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Patients With Stable CVD</title>
          <description>DAPT loading dose (Ticagrelor (180 mg) + ASA (325 mg)); DAPT maintenance therapy (Ticagrelor (90 mg BID) + ASA (81 mg OD), for one week (in same patients)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Study design is partly in vitro as testing of study aims (reversing effects of antiplatelet therapy by adding fresh platelets in different concentrations and at different times) would be nearly impossible using an in vivo study design.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Juan J. Badimon</name_or_title>
      <organization>Atherothrombosis Research Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai</organization>
      <email>Juan.Badimon@mssm.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02201394
org study id: GCO 13-1802
nct id: NCT02201394
lead sponsor: 
collaborator: 
has dmc: Yes
Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary
      artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to
      wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to
      shorten this period could be useful. The present study aims to investigate the possibility of
      reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets.
      Fresh platelets will be added to blood samples of treated patients in varying concentrations
      at specific timepoints to determine the time and amount of fresh platelets needed to
      normalize platelet reactivity in the treated samples.
The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines
      for ACS patients requiring CABG surgery after treatment with dual antiplatelet therapy
      recommend delaying surgery for 5-7 days after discontinuation of therapy, to allow for the
      dissipation of its antiplatelet effects. This treatment-devoid waiting period puts the ACS
      patients at risk for further cardiovascular events. Any means to shorten this vulnerable
      period would be of critical value. One possibility to speed up the recovery of the inhibited
      platelets is to administer infusions of fresh platelets. In fact, platelet transfusions are
      frequently administered to patients during surgery who had received prior antiplatelet
      therapy. However, the degree to which these transfusions restore platelet function in the
      recipient subjects' blood and the time from dosing when they are most effective are unknown.
      The timing is critical in scenarios where urgent surgery is required because infusion of
      platelets too soon after antiplatelet dosing could render them useless by the residual drug
      in circulation.

      The aim of the present study is to investigate the restoration of platelet function of
      ticagrelor-treated subjects by adding donor platelets to their blood. The study would have 2
      arms mimicking different clinical scenarios:

        1. Clinical Scenario 1 - Patient given a loading dose (LD) of ticagrelor in the emergency
           room, requires surgery: A single LD of ticagrelor (180 mg) with aspirin (325 mg) will be
           given to study subjects and platelet testing will be performed after addition of fresh
           platelets to their blood ex vivo. Donor platelets will be added at 4-, 6-, 24- and
           48-hours post-dose, to assess the time required for normalizing subject's platelet
           function after a LD of ticagrelor.

        2. Clinical Scenario 2 - Patient on maintenance dosing (MD) of ticagrelor, requires
           surgery: Subjects will receive ticagrelor (90 mg twice daily) with aspirin (81 mg once
           daily) for 3-7 days. After the last dose, platelet testing will be performed after
           addition of fresh platelets to their blood ex vivo, at 4-, 6-, 24- and 48-hours
           post-dose to assess the time required for normalizing subject's platelet function after
           daily treatment with ticagrelor.

      Platelet testing will be carried out using the following methodologies:

        1. Platelet Aggregation - VerifyNow P2Y12 assay.

        2. Platelet Aggregation - Multiplate Analyzer.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: P2Y12 Reaction Unit (PRU)
time frame: Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose
description: Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.
measure: Platelet Aggregation Using Multiplate Analyzer
time frame: Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose
description: Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.
arm group label: Loading dose
arm group type: Experimental
description: Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose
arm group label: Maintenance dose
arm group type: Experimental
description: Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week.
intervention type: Drug
intervention name: Ticagrelor loading dose
description: Single loading dose of Ticagrelor 180 mg
arm group label: Loading dose
other name: Brilinta
intervention type: Drug
intervention name: Aspirin loading dose
description: Single loading dose of Aspirin 325 mg
arm group label: Loading dose
other name: Acetylsalicylic acid
other name: ASA
intervention type: Drug
intervention name: Ticagrelor maintenance dose
description: Ticagrelor 90 mg twice daily x 7 days
arm group label: Maintenance dose
other name: Ticagrelor
other name: Brilinta
intervention type: Drug
intervention name: Aspirin maintenance dose
description: Aspirin 81 mg once daily x 7 days
arm group label: Maintenance dose
other name: Aspirin
other name: ASA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Juan J Badimon, PhD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Juan J Badimon
investigator title: Director, AtheroThrombosis Research Unit; Professor of Medicine
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Aspirin
mesh term: Ticagrelor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study design is partly in vitro as testing of study aims (reversing effects of antiplatelet therapy by adding fresh platelets in different concentrations and at different times) would be nearly impossible using an in vivo study design.
point of contact: 