<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/NCT02212028</url>
  </required_header>
  <id_info>
    <org_study_id>Prasugrel-CRUSH</org_study_id>
    <nct_id>NCT02212028</nct_id>
  </id_info>
  <brief_title>Pharmacological Effects of Crushing Prasugrel in STEMI Patients</brief_title>
  <official_title>Pharmacodynamic and Pharmacokinetic Profiles of Prasugrel in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Standard Versus Crushed Formulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prasugrel has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing&#xD;
      recurrent ischemic events. Prasugrel is approved in patients with ST-elevation myocardial&#xD;
      infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) at a dosage of&#xD;
      60 mg loading dose (LD) followed by 10 mg/day. However, a delay in the onset of its&#xD;
      antiplatelet effects in this particular setting has been consistently shown. administration&#xD;
      of clopidogrel and ticagrelor crushed tablets has been tested and a faster and greater&#xD;
      bioavailability compared to the whole tablets has been observed. However, if the&#xD;
      administration of a crushed prasugrel LD may overcome the above limitation is still unknown&#xD;
      and represents the aim of our study. The proposed investigation will have a prospective,&#xD;
      randomized, design in which STEMI patients undergoing primary PCI will be randomized to&#xD;
      receive two different formulation of prasugrel LD (60 mg whole tablets and 60 mg crushed&#xD;
      tablets). Pharmacodynamic testing will be performed at several time points to test our study&#xD;
      hypothesis that crushed LD regiment will achieve more prompt and enhanced platelet inhibitory&#xD;
      effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the&#xD;
      cornerstone of treatment for prevention of thrombotic events in patients with acute coronary&#xD;
      syndromes (ACS). Prasugrel, a third generation thienopyridine, is an orally administered&#xD;
      prodrug that needs single-step hepatic biotransformation into its active metabolite to&#xD;
      irreversibly block the P2Y12 receptor. Prasugrel has shown to be superior to clopidogrel, in&#xD;
      adjunct to aspirin, in preventing recurrent ischemic events. Prasugrel is approved in&#xD;
      patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous&#xD;
      coronary intervention (PCI) at a dosage of 60 mg loading dose (LD) followed by 10 mg/day.&#xD;
      However, a delay in the onset of its antiplatelet effects in this particular setting has been&#xD;
      consistently shown. The STEMI setting is characterized by conditions, such as impaired&#xD;
      absorption and hepatic metabolism, patients either intubated, in shock or unable to swallow,&#xD;
      which may affect the pharmacoki¬netic and pharmacodynamic effects of orally administered&#xD;
      antiplatelet drugs. The administration of clopidogrel and ticagrelor crushed tablets has been&#xD;
      tested and a faster and greater bioavailability compared to the whole tablets has been&#xD;
      observed. However, if the administration of a crushed prasugrel LD may overcome the above&#xD;
      limitation is still unknown and represents the aim of our study. The proposed investigation&#xD;
      will have a prospective, randomized, design in which STEMI patients undergoing primary PCI&#xD;
      will be randomized to receive two different formulation of prasugrel LD (60 mg whole tablets&#xD;
      and 60 mg crushed tablets). Pharmacodynamic testing will be performed at several time points&#xD;
      to test our study hypothesis that crushed LD regiment will achieve more prompt and enhanced&#xD;
      platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects&#xD;
      of crushed prasugrel LD and will help clinicians choose the most appropriate treatment to&#xD;
      avoid complications related to inadequate platelet inhibition in the early phase of patients&#xD;
      with STEMI undergoing primary PCI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>P2Y12 Reaction Units (PRU)</measure>
    <time_frame>2 hrs</time_frame>
    <description>The primary end-point of the study is the comparison in platelet reactivity expressed as PRU determined by VerifyNow P2Y12 between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index (PRI)</measure>
    <time_frame>2 hrs</time_frame>
    <description>The secondary end-point of the study is the comparison in platelet reactivity expressed as PRI determined by whole blood vasodilator-stimulated phosphoprotein (VASP) between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Prasugrel crush</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prasugrel 60mg loading dose as crushed tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prasugrel tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prasugrel 60 mg loading dose as whole tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prasugrel</intervention_name>
    <description>the effects of whole tablets versus crushed tablets will be compared</description>
    <arm_group_label>Prasugrel crush</arm_group_label>
    <arm_group_label>Prasugrel tablets</arm_group_label>
    <other_name>Effient</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patients with ST-elevation myocardial infarction undergoing primary PCI&#xD;
&#xD;
          -  Age between 18 and 75 years old&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Age &gt;75 years&#xD;
&#xD;
          -  Weight &lt;60 Kg&#xD;
&#xD;
          -  On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel,&#xD;
             ticagrelor) in past 7 days&#xD;
&#xD;
          -  Known allergies to aspirin or prasugrel&#xD;
&#xD;
          -  Considered at high risk for bleeding&#xD;
&#xD;
          -  History of ischemic or hemorrhagic stroke or transient ischemic attack&#xD;
&#xD;
          -  On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban,&#xD;
             apixaban)&#xD;
&#xD;
          -  Treatment with IIb/IIIa glycoprotein inhibitors&#xD;
&#xD;
          -  Fibrinolytics within 24 hours&#xD;
&#xD;
          -  Known blood dyscrasia or bleeding diathesis&#xD;
&#xD;
          -  Known platelet count &lt;80x106/mL&#xD;
&#xD;
          -  Known hemoglobin &lt;10 g/dL&#xD;
&#xD;
          -  Active bleeding&#xD;
&#xD;
          -  Hemodynamic instability&#xD;
&#xD;
          -  Known creatinine clearance &lt;30 mL/minute&#xD;
&#xD;
          -  Known severe hepatic dysfunction&#xD;
&#xD;
          -  Pregnant females*&#xD;
&#xD;
               -  Women of childbearing age must use reliable birth control (i.e. oral&#xD;
                  contraceptives) while participating in the study.&#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>Dominick Angiolillo</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</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 2015</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <results_first_submitted>November 1, 2016</results_first_submitted>
  <results_first_submitted_qc>November 1, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 28, 2016</results_first_posted>
  <last_update_submitted>November 1, 2016</last_update_submitted>
  <last_update_submitted_qc>November 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ST-elevation myocardial infarction</keyword>
  <keyword>prasugrel</keyword>
  <keyword>pharmacodynamic</keyword>
  <keyword>pharmacokinetic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prasugrel Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Between October 15, 2014, and August 12, 2015, there were a total of 123 patients presenting with a STEMI at the University of Florida Health-Jacksonville, that were screened.</recruitment_details>
      <pre_assignment_details>45 patients did not meet study entry criteria, while 78 provided their written informed consent to participate in the study and, of these, 52 were randomized. the remaining subjects were not randomized because of exclusion criteria emerged after consenting.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Prasugrel Crush</title>
          <description>Prasugrel 60mg loading dose as crushed tablets</description>
        </group>
        <group group_id="P2">
          <title>Prasugrel Tablets</title>
          <description>Prasugrel 60 mg loading dose whole tablets</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="26"/>
              </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>
      <population>Two patients in the whole tablets arm were excluded from the analysis because of missing data for the primary end point.</population>
      <group_list>
        <group group_id="B1">
          <title>Prasugrel Crush</title>
          <description>Prasugrel 60mg loading dose as crushed tablets</description>
        </group>
        <group group_id="B2">
          <title>Prasugrel Tablets</title>
          <description>Prasugrel 60 mg loading dose whole tablets</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="26"/>
            <count group_id="B2" value="24"/>
            <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="57" spread="9"/>
                    <measurement group_id="B2" value="58" spread="10"/>
                    <measurement group_id="B3" value="58" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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 group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </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="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>P2Y12 Reaction Units (PRU)</title>
        <description>The primary end-point of the study is the comparison in platelet reactivity expressed as PRU determined by VerifyNow P2Y12 between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration</description>
        <time_frame>2 hrs</time_frame>
        <population>The primary population was defined as patients who received the randomized treatment and had a valid primary end point value (PRU at 2 hours) and was considered for analysis of all endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Prasugrel Crush</title>
            <description>Prasugrel 60mg loading dose as crushed tablets</description>
          </group>
          <group group_id="O2">
            <title>Prasugrel Tablets</title>
            <description>Prasugrel 60 mg loading dose whole tablets</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units (PRU)</title>
          <description>The primary end-point of the study is the comparison in platelet reactivity expressed as PRU determined by VerifyNow P2Y12 between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration</description>
          <population>The primary population was defined as patients who received the randomized treatment and had a valid primary end point value (PRU at 2 hours) and was considered for analysis of all endpoints.</population>
          <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="26"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95" lower_limit="55" upper_limit="135"/>
                    <measurement group_id="O2" value="164" lower_limit="122" upper_limit="206"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.022</p_value>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>68</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>10</ci_lower_limit>
            <ci_upper_limit>126</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index (PRI)</title>
        <description>The secondary end-point of the study is the comparison in platelet reactivity expressed as PRI determined by whole blood vasodilator-stimulated phosphoprotein (VASP) between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration</description>
        <time_frame>2 hrs</time_frame>
        <population>The primary population was defined as patients who received the randomized treatment and had a valid primary end point value (PRU at 2 hours) and was considered for analysis of all endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Prasugrel Crush</title>
            <description>Prasugrel 60mg loading dose as crushed tablets</description>
          </group>
          <group group_id="O2">
            <title>Prasugrel Tablets</title>
            <description>Prasugrel 60 mg loading dose whole tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index (PRI)</title>
          <description>The secondary end-point of the study is the comparison in platelet reactivity expressed as PRI determined by whole blood vasodilator-stimulated phosphoprotein (VASP) between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration</description>
          <population>The primary population was defined as patients who received the randomized treatment and had a valid primary end point value (PRU at 2 hours) and was considered for analysis of all endpoints.</population>
          <units>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="26"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33" lower_limit="20" upper_limit="46"/>
                    <measurement group_id="O2" value="61" lower_limit="47" upper_limit="75"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 days</time_frame>
      <desc>In-hospital adverse events, including ischemic and bleeding complications were recorded.</desc>
      <group_list>
        <group group_id="E1">
          <title>Prasugrel Crush</title>
          <description>Prasugrel 60mg loading dose as crushed tablets</description>
        </group>
        <group group_id="E2">
          <title>Prasugrel Tablets</title>
          <description>Prasugrel 60 mg loading dose whole tablets</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>SNOMED CT</default_vocab>
        <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="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Minor bleeding</sub_title>
                <description>There was only 1 minor bleeding event (hematuria) in the crushed prasugrel arm, which did not required drug discontinuation.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </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, MD, PhD</name_or_title>
      <organization>University of Florida College of Medicine-Jacksonville</organization>
      <phone>+1-904-244-3933</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/NCT02212028
org study id: Prasugrel-CRUSH
nct id: NCT02212028
lead sponsor: 
has dmc: Yes
Prasugrel has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing
      recurrent ischemic events. Prasugrel is approved in patients with ST-elevation myocardial
      infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) at a dosage of
      60 mg loading dose (LD) followed by 10 mg/day. However, a delay in the onset of its
      antiplatelet effects in this particular setting has been consistently shown. administration
      of clopidogrel and ticagrelor crushed tablets has been tested and a faster and greater
      bioavailability compared to the whole tablets has been observed. However, if the
      administration of a crushed prasugrel LD may overcome the above limitation is still unknown
      and represents the aim of our study. The proposed investigation will have a prospective,
      randomized, design in which STEMI patients undergoing primary PCI will be randomized to
      receive two different formulation of prasugrel LD (60 mg whole tablets and 60 mg crushed
      tablets). Pharmacodynamic testing will be performed at several time points to test our study
      hypothesis that crushed LD regiment will achieve more prompt and enhanced platelet inhibitory
      effects.
Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the
      cornerstone of treatment for prevention of thrombotic events in patients with acute coronary
      syndromes (ACS). Prasugrel, a third generation thienopyridine, is an orally administered
      prodrug that needs single-step hepatic biotransformation into its active metabolite to
      irreversibly block the P2Y12 receptor. Prasugrel has shown to be superior to clopidogrel, in
      adjunct to aspirin, in preventing recurrent ischemic events. Prasugrel is approved in
      patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous
      coronary intervention (PCI) at a dosage of 60 mg loading dose (LD) followed by 10 mg/day.
      However, a delay in the onset of its antiplatelet effects in this particular setting has been
      consistently shown. The STEMI setting is characterized by conditions, such as impaired
      absorption and hepatic metabolism, patients either intubated, in shock or unable to swallow,
      which may affect the pharmacoki¬netic and pharmacodynamic effects of orally administered
      antiplatelet drugs. The administration of clopidogrel and ticagrelor crushed tablets has been
      tested and a faster and greater bioavailability compared to the whole tablets has been
      observed. However, if the administration of a crushed prasugrel LD may overcome the above
      limitation is still unknown and represents the aim of our study. The proposed investigation
      will have a prospective, randomized, design in which STEMI patients undergoing primary PCI
      will be randomized to receive two different formulation of prasugrel LD (60 mg whole tablets
      and 60 mg crushed tablets). Pharmacodynamic testing will be performed at several time points
      to test our study hypothesis that crushed LD regiment will achieve more prompt and enhanced
      platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects
      of crushed prasugrel LD and will help clinicians choose the most appropriate treatment to
      avoid complications related to inadequate platelet inhibition in the early phase of patients
      with STEMI undergoing primary PCI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: P2Y12 Reaction Units (PRU)
time frame: 2 hrs
description: The primary end-point of the study is the comparison in platelet reactivity expressed as PRU determined by VerifyNow P2Y12 between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration
measure: Platelet Reactivity Index (PRI)
time frame: 2 hrs
description: The secondary end-point of the study is the comparison in platelet reactivity expressed as PRI determined by whole blood vasodilator-stimulated phosphoprotein (VASP) between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration
arm group label: Prasugrel crush
arm group type: Experimental
description: Prasugrel 60mg loading dose as crushed tablets
arm group label: Prasugrel tablets
arm group type: Active Comparator
description: Prasugrel 60 mg loading dose as whole tablets
intervention type: Drug
intervention name: prasugrel
description: the effects of whole tablets versus crushed tablets will be compared
arm group label: Prasugrel crush
arm group label: Prasugrel tablets
other name: Effient
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dominick Angiolillo
role: Principal Investigator
affiliation: University of Florida
facility: 
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: ST Elevation Myocardial Infarction
mesh term: Prasugrel Hydrochloride
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 