<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/NCT03247738</url>
  </required_header>
  <id_info>
    <org_study_id>IIS CHI001 WIRB</org_study_id>
    <nct_id>NCT03247738</nct_id>
  </id_info>
  <brief_title>Platelet Inhibition With Cangrelor and Crushed Ticagrelor in STEMI</brief_title>
  <acronym>CANTIC</acronym>
  <official_title>Platelet Inhibition With CANgrelor and Crushed TICagrelor in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: The CANTIC Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chiesi Farmaceutici S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor&#xD;
      inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves&#xD;
      their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and&#xD;
      because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the&#xD;
      use of crushed tablets, up to one-third of patients may still have high on-treatment platelet&#xD;
      reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these&#xD;
      oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and&#xD;
      offset of action associated with a greater reduction in ischemic events compared with&#xD;
      clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have&#xD;
      explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of&#xD;
      cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor&#xD;
      inhibitor and how this compares with a crushed formulation of the oral drug is unexplored.&#xD;
      The aim of this prospective randomized study is to investigate the PD effects of cangrelor in&#xD;
      STEMI patients undergoing PPCI treated with crushed ticagrelor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor&#xD;
      inhibitors, including prasugrel and ticagrelor, which require more than 2 hours to exert&#xD;
      their full antiplatelet effects, and thus exposing these high-risk patients to an increased&#xD;
      risk of early thrombotic complications. The mechanism of this delayed onset of antiplatelet&#xD;
      effect is likely multifactorial due to the presence in the setting of STEMI of specific&#xD;
      conditions that translate into delayed drug absorption which in turn affect the&#xD;
      pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oral P2Y12 receptor inhibitors.&#xD;
      Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug&#xD;
      absorption and onset of antiplatelet effects and because of this, it is commonly used in&#xD;
      STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third&#xD;
      of patients may still have high on-treatment platelet reactivity (HPR) within the first 2&#xD;
      hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent&#xD;
      intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a&#xD;
      greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve&#xD;
      patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI&#xD;
      subjects treated with clopidogrel and the clinical profile of cangrelor among patients&#xD;
      treated with prasugrel or ticagrelor is currently unknown. This is noteworthy because ACS&#xD;
      patients, in particular STEMI undergoing PPCI, are commonly treated with either prasugrel or&#xD;
      ticagrelor. PD investigations conducted in vitro or ex vivo in stable patients have shown&#xD;
      cangrelor to be associated with enhanced platelet inhibition compared with that induced by&#xD;
      prasugrel and ticagrelor. However, the PD effects of cangrelor in STEMI patients undergoing&#xD;
      PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a&#xD;
      crushed formulation of the oral drug is unexplored. The aim of this prospective randomized&#xD;
      study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated&#xD;
      with crushed ticagrelor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 20, 2017</start_date>
  <completion_date type="Actual">December 13, 2018</completion_date>
  <primary_completion_date type="Actual">December 13, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Platelet Reactivity Measured by VerifyNow PRU</measure>
    <time_frame>30 minutes</time_frame>
    <description>Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Platelet reactivity at 30 minutes after starting cangrelor or placebo measured by VASP and reported as platelet reactivity index (PRI%). Higher PRI% means higher platelet reactivity.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>ST Segment Elevation Myocardial Infarction</condition>
  <condition>Percutaneous Coronary Intervention</condition>
  <arm_group>
    <arm_group_label>Cangrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline bolus and infusion for 2 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cangrelor</intervention_name>
    <description>Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
    <arm_group_label>Cangrelor</arm_group_label>
    <other_name>Kangreal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patients with STEMI undergoing primary PPCI&#xD;
&#xD;
          -  Age &gt; 18 years old&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Inability to provide written informed consent&#xD;
&#xD;
          -  Known history of prior intracranial bleeding&#xD;
&#xD;
          -  On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel,&#xD;
             ticagrelor) in the prior 10 days&#xD;
&#xD;
          -  Known allergies to aspirin, ticagrelor or cangrelor&#xD;
&#xD;
          -  On treatment with oral anticoagulant&#xD;
&#xD;
          -  Treatment with glycoprotein IIb/IIIa inhibitors&#xD;
&#xD;
          -  Fibrinolytics within 24 hours&#xD;
&#xD;
          -  Active bleeding&#xD;
&#xD;
          -  High risk of bleeding&#xD;
&#xD;
          -  Known platelet count &lt;80x106/mL&#xD;
&#xD;
          -  Known hemoglobin &lt;10 g/dL&#xD;
&#xD;
          -  Intubated patients (prior to randomization)&#xD;
&#xD;
          -  Known creatinine clearance &lt;30 mL/minute or on hemodialysis.&#xD;
&#xD;
          -  Known severe hepatic dysfunction&#xD;
&#xD;
          -  Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker&#xD;
             protection&#xD;
&#xD;
          -  Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction&#xD;
             with ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin,&#xD;
             nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and&#xD;
             telithromizycin.&#xD;
&#xD;
          -  Pregnant or lactating females.&#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>Dominick Angiolillo, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida College of Medicine-Jacksonville</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <results_first_submitted>January 10, 2020</results_first_submitted>
  <results_first_submitted_qc>January 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 6, 2020</results_first_posted>
  <last_update_submitted>August 26, 2020</last_update_submitted>
  <last_update_submitted_qc>August 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ticagrelor</keyword>
  <keyword>cangrelor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cangrelor</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT03247738/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Between December 10, 2017 and July 17, 2018, there were a total of 99 STEMI patients with intent to undergo P-PCI that presented to our Institution, of whom 69 provided their written informed consent to participate in the study.</recruitment_details>
      <pre_assignment_details>19 patients were not randomized because PCI was not performed or had newly identified exclusion criteria</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cangrelor</title>
          <description>Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours&#xD;
Cangrelor: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Normal saline bolus and infusion for 2 hours&#xD;
Placebo: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cangrelor</title>
          <description>Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours&#xD;
Cangrelor: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Normal saline bolus and infusion for 2 hours&#xD;
Placebo: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="50"/>
          </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="60" spread="11"/>
                    <measurement group_id="B2" value="60" spread="10"/>
                    <measurement group_id="B3" value="60" spread="10"/>
                  </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="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Radial access</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Use of glycoprotein IIb/IIIa inhibitors</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Platelet Reactivity Measured by VerifyNow PRU</title>
        <description>Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)</description>
        <time_frame>30 minutes</time_frame>
        <population>The analyzed patients included all patients with pharmacodynamic data and without a major protocol deviation thought to affect the pharmacodynamic effects of ticagrelor or cangrelor.</population>
        <group_list>
          <group group_id="O1">
            <title>Cangrelor</title>
            <description>Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours&#xD;
Cangrelor: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline bolus and infusion for 2 hours&#xD;
Placebo: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Measured by VerifyNow PRU</title>
          <description>Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)</description>
          <population>The analyzed patients included all patients with pharmacodynamic data and without a major protocol deviation thought to affect the pharmacodynamic effects of ticagrelor or cangrelor.</population>
          <units>P2Y12 reaction units (PRU)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63" lower_limit="32" upper_limit="93"/>
                    <measurement group_id="O2" value="214" lower_limit="183" upper_limit="245"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>The primary end point of our study was the comparison of platelet reactivity measured by VerifyNow PRU between cangrelor and placebo at 30 minutes after drugs were administered at the start of PCI. Assuming a common standard deviation of 70 PRU, a sample size of 20 patients per group would allow detection of a 70 PRU difference between groups with 85% power and a two-sided α = 0.05. Considering the 2 arms and a possible 25% rate of invalid PD results we planned to randomize up to 50 patients.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>the baseline value of platelet reactivity used as a covariate</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>152</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>108</ci_lower_limit>
            <ci_upper_limit>195</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)</title>
        <description>Platelet reactivity at 30 minutes after starting cangrelor or placebo measured by VASP and reported as platelet reactivity index (PRI%). Higher PRI% means higher platelet reactivity.</description>
        <time_frame>30 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cangrelor</title>
            <description>Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours&#xD;
Cangrelor: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline bolus and infusion for 2 hours&#xD;
Placebo: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)</title>
          <description>Platelet reactivity at 30 minutes after starting cangrelor or placebo measured by VASP and reported as platelet reactivity index (PRI%). Higher PRI% means higher platelet reactivity.</description>
          <units>platelet reactivity index (PRI)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29" lower_limit="18" upper_limit="39"/>
                    <measurement group_id="O2" value="72" lower_limit="61" upper_limit="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Until time of discharge</time_frame>
      <desc>The safety population was composed of all patients exposed to at least one dose of study medication (any time from randomization until completion of the study). Any adverse event until time of discharge was recorded.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cangrelor</title>
          <description>Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours&#xD;
Cangrelor: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Normal saline bolus and infusion for 2 hours&#xD;
Placebo: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute stent thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>minor bleeding</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="25"/>
              </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>
    <point_of_contact>
      <name_or_title>Dominick J. Angiolillo</name_or_title>
      <organization>University of Florida College of Medicine, Jacksonville</organization>
      <phone>9042443933</phone>
      <email>dominick.angiolillo@jax.ufl.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/NCT03247738
org study id: IIS CHI001 WIRB
nct id: NCT03247738
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor
      inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves
      their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and
      because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the
      use of crushed tablets, up to one-third of patients may still have high on-treatment platelet
      reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these
      oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and
      offset of action associated with a greater reduction in ischemic events compared with
      clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have
      explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of
      cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor
      inhibitor and how this compares with a crushed formulation of the oral drug is unexplored.
      The aim of this prospective randomized study is to investigate the PD effects of cangrelor in
      STEMI patients undergoing PPCI treated with crushed ticagrelor.
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor
      inhibitors, including prasugrel and ticagrelor, which require more than 2 hours to exert
      their full antiplatelet effects, and thus exposing these high-risk patients to an increased
      risk of early thrombotic complications. The mechanism of this delayed onset of antiplatelet
      effect is likely multifactorial due to the presence in the setting of STEMI of specific
      conditions that translate into delayed drug absorption which in turn affect the
      pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oral P2Y12 receptor inhibitors.
      Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug
      absorption and onset of antiplatelet effects and because of this, it is commonly used in
      STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third
      of patients may still have high on-treatment platelet reactivity (HPR) within the first 2
      hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent
      intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a
      greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve
      patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI
      subjects treated with clopidogrel and the clinical profile of cangrelor among patients
      treated with prasugrel or ticagrelor is currently unknown. This is noteworthy because ACS
      patients, in particular STEMI undergoing PPCI, are commonly treated with either prasugrel or
      ticagrelor. PD investigations conducted in vitro or ex vivo in stable patients have shown
      cangrelor to be associated with enhanced platelet inhibition compared with that induced by
      prasugrel and ticagrelor. However, the PD effects of cangrelor in STEMI patients undergoing
      PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a
      crushed formulation of the oral drug is unexplored. The aim of this prospective randomized
      study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated
      with crushed ticagrelor.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Platelet Reactivity Measured by VerifyNow PRU
time frame: 30 minutes
description: Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)
measure: Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)
time frame: 30 minutes
description: Platelet reactivity at 30 minutes after starting cangrelor or placebo measured by VASP and reported as platelet reactivity index (PRI%). Higher PRI% means higher platelet reactivity.
arm group label: Cangrelor
arm group type: Experimental
description: Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal saline bolus and infusion for 2 hours
intervention type: Drug
intervention name: Cangrelor
description: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.
arm group label: Cangrelor
other name: Kangreal
intervention type: Other
intervention name: Placebo
description: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dominick Angiolillo, MD, PhD
role: Principal Investigator
affiliation: University of Florida College of Medicine-Jacksonville
facility: 
country: United States
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: Cangrelor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 