<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/NCT03822377</url>
  </required_header>
  <id_info>
    <org_study_id>ESR-17-13174</org_study_id>
    <secondary_id>2018-001790-25</secondary_id>
    <nct_id>NCT03822377</nct_id>
  </id_info>
  <brief_title>Ticagrelor Administered as Standard Tablet or Orodispersible Formulation</brief_title>
  <acronym>TASTER</acronym>
  <official_title>Ticagrelor Administered as Standard Tablet or orodispersiblE foRmulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero Universitaria di Sassari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Azienda Ospedaliero Universitaria di Sassari</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized clinical study evaluating superiority in platelet inhibition after administration&#xD;
      of Ticagrelor 180 mg loading dose as an orodispersible formulation versus traditional coated&#xD;
      tablets in patients admitted for ST elevation myocardial infarction or very high-risk non-ST&#xD;
      elevation myocardial infarction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for&#xD;
      patients with acute ST-segment elevation myocardial infarction (STEMI). Additional&#xD;
      antithrombotic therapy prior or during intervention plays an important role in the short- and&#xD;
      long-term outcomes after PPCI. Oral antiplatelet therapy including a platelet P2Y12 receptor&#xD;
      inhibitors is a cornerstone of antithrombotic treatment in patients with acute coronary&#xD;
      syndromes. Prasugrel and Ticagrelor have been shown to be superior to Clopidogrel in patients&#xD;
      with STEMI in reduction of ischemic complication without any increase in the bleeding risk&#xD;
      and with a significant reduction in the stent thrombosis rate. Nevertheless, in STEMI&#xD;
      patients, pharmacodynamic studies showed prasugrel and ticagrelor oral loading dose (LD)&#xD;
      provided a suboptimal platelet inhibition in the first hours after LD, and at least 4 hours&#xD;
      are required to achieve and effective platelet aggregation inhibition in the majority of&#xD;
      patients, in part due to slowed gut motility caused by morphine use. Orodispersible tablet&#xD;
      (ODT) is a different tablet formulation that disperses upon contact with the moist mucosal&#xD;
      surfaces of the oral cavity and quickly release its components before swallowing; thus local&#xD;
      drug dissolution and absorption as well as onset of clinical effect can be obtained&#xD;
      conveniently easily and quickly by bypassing gastrointestinal tract. Recently, Ticagrelor 90&#xD;
      mg ODT has become available and bioequivalence studies on healthy volunteers documented its&#xD;
      effectiveness with consequent approval by European Medicine Agency of this formulation which&#xD;
      is currently available on the market. Thus, the aim of the present study is to evaluate the&#xD;
      superiority in platelet inhibition with 180 mg Ticagrelor loading dose (LD) administered as&#xD;
      ODTs as compared with standard formulation, among patients with STEMI or very high-risk&#xD;
      NSTEMI undergoing immediate PCI. Primary objective consists in evaluating platelet reactivity&#xD;
      1 hour after Ticagrelor loading dose by VerifyNow test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 27, 2019</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 31, 2020</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Comparison of platelet inhibition at different timepoints between 65 patients in the treatment arm (receiving orodispersible formulation of ticagrelor loading dose) versus 65 patients in the control arm (receiving standard coated formulation of ticagrelor loading dose). Randomization will be further stratified according to morphine use.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Site investigators performing platelet function tests will be blinded regarding patient randomization arm and the blood samples will be fully anonymized.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of Platelet Inhibition</measure>
    <time_frame>1 hour</time_frame>
    <description>Platelet reactivity will be measured by VerifyNow test 1 hour after Ticagrelor loading dose (LD) administered as orodispersible tablets as compared with standard formulation in 130 patients with STEMI or very high-risk NSTEMI undergoing immediate PCI.&#xD;
The VerifyNow PRU Test is designed to measure P2Y12 receptor blockade. Results of the PRU Tests are reported as P2Y12 Reaction Units (PRU). PRU measures the extent of platelet aggregation in the presence of a P2Y12 inhibitor. Lower PRU levels are associated with expected antiplatelet effect.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Patients With Insufficient Antiaggregation</measure>
    <time_frame>1 hour</time_frame>
    <description>The percent of patients with a high residual platelet reactivity (PRU &gt; 208 by VerifyNow test), thus not adequately antiaggregated, 1 hour after Ticagrelor LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Residual Platelet Reactivity at Various Timepoints</measure>
    <time_frame>2, 4 and 6 hours</time_frame>
    <description>Residual platelet reactivity (PRU) at 2, 4 and 6 hours measured by VerifyNow test to assess antiplatelet effect of P2Y12 inhibitors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Relevant Bleeding Events</measure>
    <time_frame>30 days</time_frame>
    <description>Actionable bleeding events across the two different regimens of Ticagrelor administration, requiring diagnostic studies, hospitalization, or treatment by a health care professional (BARC type 2 or higher)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Morphine-ticagrelor Interaction</measure>
    <time_frame>6 hours</time_frame>
    <description>Potential morphine-ticagrelor interaction will be assessed by stratified randomization according to morphine use</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of Adverse Events Occurring During Hospital Stay</measure>
    <time_frame>Until discharge from the hospital (usually up to 7 days)</time_frame>
    <description>Combined ticagrelor administration-related adverse events defined as in-hospital ≥2 BARC bleedings, dyspnea, ventricular pauses, allergic reactions, or vomit</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">130</enrollment>
  <condition>ST Elevation Myocardial Infarction</condition>
  <condition>NSTEMI - Non-ST Segment Elevation MI</condition>
  <arm_group>
    <arm_group_label>Ticagrelor orodispersible tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ticagrelor standard tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor orodispersible tablets</intervention_name>
    <description>Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
    <arm_group_label>Ticagrelor orodispersible tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor standard tablets</intervention_name>
    <description>Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
    <arm_group_label>Ticagrelor standard tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients presenting within 12 hours from the onset of symptoms with STEMI or very&#xD;
             high-risk NSTEMI referred for immediate (&lt; 2 hours) angiography. Very high-risk NSTEMI&#xD;
             patients include patients with haemodynamic instability or cardiogenic shock, heart&#xD;
             failure, life-threatening arrhythmias or resuscitated cardiac arrest, intermittent&#xD;
             ST-segment elevation, or ongoing chest pain.&#xD;
&#xD;
          2. Informed, written consent&#xD;
&#xD;
          3. Male or female patients, aged ≥ 18 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt; 18 years&#xD;
&#xD;
          2. Active bleeding; bleeding diathesis; coagulopathy&#xD;
&#xD;
          3. History of gastrointestinal or genitourinary bleeding &lt;2 months&#xD;
&#xD;
          4. Major surgery in the last 6 weeks&#xD;
&#xD;
          5. History of intracranial bleeding or structural abnormalities&#xD;
&#xD;
          6. Suspected aortic dissection&#xD;
&#xD;
          7. Administration in the week before the index event of clopidogrel, ticlopidine,&#xD;
             prasugrel, ticagrelor, thrombolytics, bivalirudin, low-molecular weight heparin or&#xD;
             fondaparinux.&#xD;
&#xD;
          8. Concomitant oral or IV therapy with strong CYP3A inhibitors or strong CYP3A inducers,&#xD;
             CYP3A with narrow therapeutic window&#xD;
&#xD;
          9. Known relevant hematological deviations: Hb &lt;10 g/dl, Thromb. &lt;100x10^9/l&#xD;
&#xD;
         10. Use of warfarin or new oral anticoagulant derivatives within the last 7 days&#xD;
&#xD;
         11. Known severe liver disease, severe renal failure&#xD;
&#xD;
         12. Allergy or hypersensitivity to ticagrelor or any of the excipients.&#xD;
&#xD;
         13. Pregnancy or lactation&#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>Guido Parodi, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardiologia Clinica e Interventistica - AOU Sassari</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cardiologia Clinica e Interventistica - AOU Sassari</name>
      <address>
        <city>Sassari</city>
        <zip>07100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <results_first_submitted>July 17, 2021</results_first_submitted>
  <results_first_submitted_qc>August 12, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 8, 2021</results_first_posted>
  <last_update_submitted>August 12, 2021</last_update_submitted>
  <last_update_submitted_qc>August 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliero Universitaria di Sassari</investigator_affiliation>
    <investigator_full_name>Prof. Guido Parodi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <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>Ticagrelor</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>January 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03822377/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ticagrelor Orodispersible Tablets</title>
          <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
        </group>
        <group group_id="P2">
          <title>Ticagrelor Standard Tablets</title>
          <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="65"/>
                <participants group_id="P2" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="65"/>
                <participants group_id="P2" count="65"/>
              </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>Ticagrelor Orodispersible Tablets</title>
          <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
        </group>
        <group group_id="B2">
          <title>Ticagrelor Standard Tablets</title>
          <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</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="65"/>
            <count group_id="B2" value="65"/>
            <count group_id="B3" value="130"/>
          </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="64.0" spread="10.0"/>
                    <measurement group_id="B2" value="63.0" spread="10.0"/>
                    <measurement group_id="B3" value="63.5" spread="10.0"/>
                  </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="17"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="105"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="130"/>
                  </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>Evaluation of Platelet Inhibition</title>
        <description>Platelet reactivity will be measured by VerifyNow test 1 hour after Ticagrelor loading dose (LD) administered as orodispersible tablets as compared with standard formulation in 130 patients with STEMI or very high-risk NSTEMI undergoing immediate PCI.&#xD;
The VerifyNow PRU Test is designed to measure P2Y12 receptor blockade. Results of the PRU Tests are reported as P2Y12 Reaction Units (PRU). PRU measures the extent of platelet aggregation in the presence of a P2Y12 inhibitor. Lower PRU levels are associated with expected antiplatelet effect.</description>
        <time_frame>1 hour</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor Orodispersible Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Standard Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of Platelet Inhibition</title>
          <description>Platelet reactivity will be measured by VerifyNow test 1 hour after Ticagrelor loading dose (LD) administered as orodispersible tablets as compared with standard formulation in 130 patients with STEMI or very high-risk NSTEMI undergoing immediate PCI.&#xD;
The VerifyNow PRU Test is designed to measure P2Y12 receptor blockade. Results of the PRU Tests are reported as P2Y12 Reaction Units (PRU). PRU measures the extent of platelet aggregation in the presence of a P2Y12 inhibitor. Lower PRU levels are associated with expected antiplatelet effect.</description>
          <units>P2Y12 Reaction Units (PRU)</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94" lower_limit="35" upper_limit="193"/>
                    <measurement group_id="O2" value="141" lower_limit="8" upper_limit="197"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Patients With Insufficient Antiaggregation</title>
        <description>The percent of patients with a high residual platelet reactivity (PRU &gt; 208 by VerifyNow test), thus not adequately antiaggregated, 1 hour after Ticagrelor LD.</description>
        <time_frame>1 hour</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Experimental Arm</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Patients With Insufficient Antiaggregation</title>
          <description>The percent of patients with a high residual platelet reactivity (PRU &gt; 208 by VerifyNow test), thus not adequately antiaggregated, 1 hour after Ticagrelor LD.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                    <measurement group_id="O2" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Residual Platelet Reactivity at Various Timepoints</title>
        <description>Residual platelet reactivity (PRU) at 2, 4 and 6 hours measured by VerifyNow test to assess antiplatelet effect of P2Y12 inhibitors</description>
        <time_frame>2, 4 and 6 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor Orodispersible Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Standard Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Residual Platelet Reactivity at Various Timepoints</title>
          <description>Residual platelet reactivity (PRU) at 2, 4 and 6 hours measured by VerifyNow test to assess antiplatelet effect of P2Y12 inhibitors</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Relevant Bleeding Events</title>
        <description>Actionable bleeding events across the two different regimens of Ticagrelor administration, requiring diagnostic studies, hospitalization, or treatment by a health care professional (BARC type 2 or higher)</description>
        <time_frame>30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor Orodispersible Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Standard Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Relevant Bleeding Events</title>
          <description>Actionable bleeding events across the two different regimens of Ticagrelor administration, requiring diagnostic studies, hospitalization, or treatment by a health care professional (BARC type 2 or higher)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Morphine-ticagrelor Interaction</title>
        <description>Potential morphine-ticagrelor interaction will be assessed by stratified randomization according to morphine use</description>
        <time_frame>6 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ticagrelor Orodispersible Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
          </group>
          <group group_id="O2">
            <title>Ticagrelor Standard Tablets</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Morphine-ticagrelor Interaction</title>
          <description>Potential morphine-ticagrelor interaction will be assessed by stratified randomization according to morphine use</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Incidence of Adverse Events Occurring During Hospital Stay</title>
        <description>Combined ticagrelor administration-related adverse events defined as in-hospital ≥2 BARC bleedings, dyspnea, ventricular pauses, allergic reactions, or vomit</description>
        <time_frame>Until discharge from the hospital (usually up to 7 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Experimental Arm</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events Occurring During Hospital Stay</title>
          <description>Combined ticagrelor administration-related adverse events defined as in-hospital ≥2 BARC bleedings, dyspnea, ventricular pauses, allergic reactions, or vomit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ticagrelor Orodispersible Tablets</title>
          <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.&#xD;
Ticagrelor orodispersible tablets: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.</description>
        </group>
        <group group_id="E2">
          <title>Ticagrelor Standard Tablets</title>
          <description>STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.&#xD;
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.&#xD;
Ticagrelor pills: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.</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="0" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Reinfarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="65"/>
              </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="14" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Combined ticagrelor administration-related adverse events defined as in-hospital ≥2 BARC bleedings,</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Prof. Guido Parodi</name_or_title>
      <organization>Cardiology Clinic, Sassari University Hospital, Sassari, Italy</organization>
      <phone>0039 ext 792830626</phone>
      <email>parodiguido@gmail.com</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/NCT03822377
org study id: ESR-17-13174
secondary id: 2018-001790-25
nct id: NCT03822377
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Randomized clinical study evaluating superiority in platelet inhibition after administration
      of Ticagrelor 180 mg loading dose as an orodispersible formulation versus traditional coated
      tablets in patients admitted for ST elevation myocardial infarction or very high-risk non-ST
      elevation myocardial infarction.
Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for
      patients with acute ST-segment elevation myocardial infarction (STEMI). Additional
      antithrombotic therapy prior or during intervention plays an important role in the short- and
      long-term outcomes after PPCI. Oral antiplatelet therapy including a platelet P2Y12 receptor
      inhibitors is a cornerstone of antithrombotic treatment in patients with acute coronary
      syndromes. Prasugrel and Ticagrelor have been shown to be superior to Clopidogrel in patients
      with STEMI in reduction of ischemic complication without any increase in the bleeding risk
      and with a significant reduction in the stent thrombosis rate. Nevertheless, in STEMI
      patients, pharmacodynamic studies showed prasugrel and ticagrelor oral loading dose (LD)
      provided a suboptimal platelet inhibition in the first hours after LD, and at least 4 hours
      are required to achieve and effective platelet aggregation inhibition in the majority of
      patients, in part due to slowed gut motility caused by morphine use. Orodispersible tablet
      (ODT) is a different tablet formulation that disperses upon contact with the moist mucosal
      surfaces of the oral cavity and quickly release its components before swallowing; thus local
      drug dissolution and absorption as well as onset of clinical effect can be obtained
      conveniently easily and quickly by bypassing gastrointestinal tract. Recently, Ticagrelor 90
      mg ODT has become available and bioequivalence studies on healthy volunteers documented its
      effectiveness with consequent approval by European Medicine Agency of this formulation which
      is currently available on the market. Thus, the aim of the present study is to evaluate the
      superiority in platelet inhibition with 180 mg Ticagrelor loading dose (LD) administered as
      ODTs as compared with standard formulation, among patients with STEMI or very high-risk
      NSTEMI undergoing immediate PCI. Primary objective consists in evaluating platelet reactivity
      1 hour after Ticagrelor loading dose by VerifyNow test.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Comparison of platelet inhibition at different timepoints between 65 patients in the treatment arm (receiving orodispersible formulation of ticagrelor loading dose) versus 65 patients in the control arm (receiving standard coated formulation of ticagrelor loading dose). Randomization will be further stratified according to morphine use.
primary purpose: Treatment
masking: Single (Investigator)
masking description: Site investigators performing platelet function tests will be blinded regarding patient randomization arm and the blood samples will be fully anonymized.
measure: Evaluation of Platelet Inhibition
time frame: 1 hour
description: Platelet reactivity will be measured by VerifyNow test 1 hour after Ticagrelor loading dose (LD) administered as orodispersible tablets as compared with standard formulation in 130 patients with STEMI or very high-risk NSTEMI undergoing immediate PCI.
The VerifyNow PRU Test is designed to measure P2Y12 receptor blockade. Results of the PRU Tests are reported as P2Y12 Reaction Units (PRU). PRU measures the extent of platelet aggregation in the presence of a P2Y12 inhibitor. Lower PRU levels are associated with expected antiplatelet effect.
measure: Percent of Patients With Insufficient Antiaggregation
time frame: 1 hour
description: The percent of patients with a high residual platelet reactivity (PRU > 208 by VerifyNow test), thus not adequately antiaggregated, 1 hour after Ticagrelor LD.
measure: Number of Participants With Residual Platelet Reactivity at Various Timepoints
time frame: 2, 4 and 6 hours
description: Residual platelet reactivity (PRU) at 2, 4 and 6 hours measured by VerifyNow test to assess antiplatelet effect of P2Y12 inhibitors
measure: Number of Participants With Clinically Relevant Bleeding Events
time frame: 30 days
description: Actionable bleeding events across the two different regimens of Ticagrelor administration, requiring diagnostic studies, hospitalization, or treatment by a health care professional (BARC type 2 or higher)
measure: Number of Participants With Morphine-ticagrelor Interaction
time frame: 6 hours
description: Potential morphine-ticagrelor interaction will be assessed by stratified randomization according to morphine use
measure: Incidence of Adverse Events Occurring During Hospital Stay
time frame: Until discharge from the hospital (usually up to 7 days)
description: Combined ticagrelor administration-related adverse events defined as in-hospital ≥2 BARC bleedings, dyspnea, ventricular pauses, allergic reactions, or vomit
arm group label: Ticagrelor orodispersible tablets
arm group type: Experimental
description: STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets.
Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.
arm group label: Ticagrelor standard tablets
arm group type: Active Comparator
description: STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets.
Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.
intervention type: Drug
intervention name: Ticagrelor orodispersible tablets
description: Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.
arm group label: Ticagrelor orodispersible tablets
intervention type: Drug
intervention name: Ticagrelor standard tablets
description: Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.
arm group label: Ticagrelor standard tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Guido Parodi, Professor
role: Principal Investigator
affiliation: Cardiologia Clinica e Interventistica - AOU Sassari
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliero Universitaria di Sassari
investigator full name: Prof. Guido Parodi
investigator title: Professor
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: Ticagrelor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 