<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/NCT02217878</url>
  </required_header>
  <id_info>
    <org_study_id>CMUMK202</org_study_id>
    <nct_id>NCT02217878</nct_id>
  </id_info>
  <brief_title>Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction</brief_title>
  <acronym>IMPRESSION</acronym>
  <official_title>A Randomized, Double-blind Study Evaluating the Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor and Its Active Metabolite (AR-C124910XX) in Patients With ST-segment Elevation Myocardial Infarction and Non-ST-segment Elevation Myocardial Infarction.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Collegium Medicum w Bydgoszczy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Collegium Medicum w Bydgoszczy</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the IMPRESSION study is to determine whether intravenous administration of&#xD;
      morphine prior to ticagrelor administration in ST-segment elevation myocardial infarction&#xD;
      (STEMI) patients and in non-ST-segment elevation myocardial infarction (NSTEMI) patients&#xD;
      alters the plasma concentrations of ticagrelor and its active metabolite and whether it is&#xD;
      associated with any negative impact on the antiplatelet effect of ticagrelor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The European Society of Cardiology and American Heart Association guidelines recommend use of&#xD;
      morphine as a treatment of choice for pain relief in STEMI patients. However, this&#xD;
      recommendation, although strong, is only based on expert consensus (class of recommendation&#xD;
      I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the work&#xD;
      of breathing and reduces anxiety. On the other hand, despite its favorable analgesic and&#xD;
      sedative actions, morphine also exerts adverse effects, which include hypotension,&#xD;
      bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility.&#xD;
      Some of the previously listed morphine's side effects could affect the intestinal absorption&#xD;
      and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are&#xD;
      concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data&#xD;
      regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting&#xD;
      are available. Therefore, evidence-based verification of morphine's influence on&#xD;
      pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX)&#xD;
      could provide a valuable insight in the knowledge regarding modern acute myocardial&#xD;
      infarction management.&#xD;
&#xD;
      Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment&#xD;
      methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration&#xD;
      of ticagrelor and its active metabolite (AR-C124910XX).&#xD;
&#xD;
      Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or NSTEMI&#xD;
      patients, we decided to perform an internal pilot study of approximately 30 patients (15&#xD;
      patients for each arm) for estimating the final sample size.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)</measure>
    <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose</time_frame>
    <description>Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)</measure>
    <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose</time_frame>
    <description>Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration of Ticagrelor</measure>
    <time_frame>12 hours</time_frame>
    <description>Maximum concentration (Cmax) of ticagrelor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration of AR-C124910XX</measure>
    <time_frame>12 hours</time_frame>
    <description>Maximum concentration (Cmax) of AR-C124910XX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration for Ticagrelor</measure>
    <time_frame>12 hours</time_frame>
    <description>Time to maximum concentration (Tmax) for ticagrelor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration for AR-C124910XX</measure>
    <time_frame>12 hours</time_frame>
    <description>Time to maximum concentration (Tmax) for AR-C124910XX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)</measure>
    <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose</time_frame>
    <description>Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)</measure>
    <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose</time_frame>
    <description>Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>prior to the initial ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>30 minutes post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>1 hour post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>2 hours post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>3 hours post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>4 hours post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>6 hours post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Reactivity Index Assessed by VASP Assay</measure>
    <time_frame>12 hours post ticagrelor dose</time_frame>
    <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>prior to the initial ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>30 minutes post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>1 hour post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>2 hours post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>3 hours post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>4 hours post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>6 hours post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</measure>
    <time_frame>12 hours post ticagrelor dose</time_frame>
    <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>prior to the initial ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>30 minutes post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>1 hour post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>2 hours post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>3 hours post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>4 hours post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>6 hours post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P2Y12 Reaction Units Assessed by VerifyNow</measure>
    <time_frame>12 hours post ticagrelor dose</time_frame>
    <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP</measure>
    <time_frame>2 hours</time_frame>
    <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA</measure>
    <time_frame>2 hours</time_frame>
    <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow</measure>
    <time_frame>2 hours</time_frame>
    <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP</measure>
    <time_frame>12 hours</time_frame>
    <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA</measure>
    <time_frame>12 hours</time_frame>
    <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow</measure>
    <time_frame>12 hours</time_frame>
    <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>ST-segment Elevation Myocardial Infarction</condition>
  <condition>Non-ST-segment Elevation Myocardial Infarction</condition>
  <condition>VA Drug Interactions</condition>
  <arm_group>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>IV bolus injection</description>
    <arm_group_label>Morphine</arm_group_label>
    <other_name>Morphine sulfate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>IV bolus injection</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sodium chloride 0,9%</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor</intervention_name>
    <description>180 mg loading dose</description>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Brilique</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  provision of informed consent prior to any study specific procedures&#xD;
&#xD;
          -  diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment&#xD;
             elevation myocardial infarction&#xD;
&#xD;
          -  male or non-pregnant female, aged 18-80 years old&#xD;
&#xD;
          -  provision of informed consent for angiography and PCI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  chest pain described by the patient as unbearable or patient's request for analgesics&#xD;
&#xD;
          -  prior morphine administration during the current STEMI or NSTEMI&#xD;
&#xD;
          -  treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before&#xD;
             the study enrollment&#xD;
&#xD;
          -  hypersensitivity to ticagrelor&#xD;
&#xD;
          -  current treatment with oral anticoagulant or chronic therapy with low-molecular-weight&#xD;
             heparin&#xD;
&#xD;
          -  active bleeding&#xD;
&#xD;
          -  history of intracranial hemorrhage&#xD;
&#xD;
          -  recent gastrointestinal bleeding (within 30 days)&#xD;
&#xD;
          -  history of coagulation disorders&#xD;
&#xD;
          -  platelet count less than &lt;100 x10^3/mcl&#xD;
&#xD;
          -  hemoglobin concentration less than 10.0 g/dl&#xD;
&#xD;
          -  history of moderate or severe hepatic impairment&#xD;
&#xD;
          -  history of major surgery or severe trauma (within 3 months)&#xD;
&#xD;
          -  patients considered by the investigator to be at risk of bradycardic events&#xD;
&#xD;
          -  second or third degree atrioventricular block during screening for eligibility&#xD;
&#xD;
          -  history of asthma or severe chronic obstructive pulmonary disease&#xD;
&#xD;
          -  patient required dialysis&#xD;
&#xD;
          -  manifest infection or inflammatory state&#xD;
&#xD;
          -  Killip class III or IV during screening for eligibility&#xD;
&#xD;
          -  respiratory failure&#xD;
&#xD;
          -  history of severe chronic heart failure (NYHA class III or IV)&#xD;
&#xD;
          -  concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole,&#xD;
             voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir,&#xD;
             nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin,&#xD;
             carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment&#xD;
&#xD;
          -  body weight below 50 kg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Prof. Jacek Kubica, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cardiology Department, Dr. A. Jurasz University Hospital</name>
      <address>
        <city>Bydgoszcz</city>
        <state>Kujawsko-pomorskie</state>
        <zip>85-094</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <results_first_submitted>February 4, 2016</results_first_submitted>
  <results_first_submitted_qc>February 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 3, 2016</results_first_posted>
  <last_update_submitted>August 12, 2017</last_update_submitted>
  <last_update_submitted_qc>August 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Collegium Medicum w Bydgoszczy</investigator_affiliation>
    <investigator_full_name>Jacek Kubica</investigator_full_name>
    <investigator_title>Prof. dr hab.</investigator_title>
  </responsible_party>
  <keyword>ST-segment elevation myocardial infarction</keyword>
  <keyword>non-ST-segment elevation myocardial infarction</keyword>
  <keyword>ticagrelor</keyword>
  <keyword>morphine</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>pharmacodynamics</keyword>
  <keyword>drug interactions</keyword>
  <keyword>VASP assay</keyword>
  <keyword>Multiple Electrode Aggregometry</keyword>
  <keyword>VerifyNow</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>Morphine</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Morphine</title>
          <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>required morphine due to chest pain</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>initial diagnosis of STEMI not confirmed</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Morphine</title>
          <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</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="35"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="70"/>
          </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="60.7" spread="10.5"/>
                    <measurement group_id="B2" value="62.5" spread="10.5"/>
                    <measurement group_id="B3" value="61.5" spread="10.3"/>
                  </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="12"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.6" spread="4.3"/>
                    <measurement group_id="B2" value="27.4" spread="4.0"/>
                    <measurement group_id="B3" value="27.5" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>STEMI</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>GP IIb/IIIa administration</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hypertension</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes mellitus</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Dyslipidaemia</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Current smoker</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior AMI</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior PCI</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior CABG</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <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>Prior non-severe heart failure</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior non-haemorrhagic stroke</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Peripheral arterial disease</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Chronic renal disease</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Chronic obstructive pulmonary disease</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gout</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)</title>
        <description>Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose</description>
        <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)</title>
          <description>Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose</description>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6307" spread="4359"/>
                    <measurement group_id="O2" value="9791" spread="5136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)</title>
        <description>Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose</description>
        <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)</title>
          <description>Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose</description>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1503" spread="1138"/>
                    <measurement group_id="O2" value="2388" spread="1555"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Concentration of Ticagrelor</title>
        <description>Maximum concentration (Cmax) of ticagrelor</description>
        <time_frame>12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Concentration of Ticagrelor</title>
          <description>Maximum concentration (Cmax) of ticagrelor</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1156" spread="771"/>
                    <measurement group_id="O2" value="1683" spread="847"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Concentration of AR-C124910XX</title>
        <description>Maximum concentration (Cmax) of AR-C124910XX</description>
        <time_frame>12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Concentration of AR-C124910XX</title>
          <description>Maximum concentration (Cmax) of AR-C124910XX</description>
          <units>ng/mL</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1085" lower_limit="508" upper_limit="1709"/>
                    <measurement group_id="O2" value="1043" lower_limit="792" upper_limit="1572"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Concentration for Ticagrelor</title>
        <description>Time to maximum concentration (Tmax) for ticagrelor</description>
        <time_frame>12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Concentration for Ticagrelor</title>
          <description>Time to maximum concentration (Tmax) for ticagrelor</description>
          <units>hours</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="3" upper_limit="12"/>
                    <measurement group_id="O2" value="2" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Concentration for AR-C124910XX</title>
        <description>Time to maximum concentration (Tmax) for AR-C124910XX</description>
        <time_frame>12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Concentration for AR-C124910XX</title>
          <description>Time to maximum concentration (Tmax) for AR-C124910XX</description>
          <units>hours</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="3" upper_limit="12"/>
                    <measurement group_id="O2" value="4" lower_limit="3" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)</title>
        <description>Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose</description>
        <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)</title>
          <description>Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose</description>
          <units>ng*h/mL</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2491" lower_limit="189" upper_limit="5764"/>
                    <measurement group_id="O2" value="5587" lower_limit="2810" upper_limit="8546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)</title>
        <description>Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose</description>
        <time_frame>prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)</title>
          <description>Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose</description>
          <units>ng*h/mL</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="472" lower_limit="0" upper_limit="1036"/>
                    <measurement group_id="O2" value="1001" lower_limit="643" upper_limit="1666"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>prior to the initial ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.5" lower_limit="82.9" upper_limit="93.5"/>
                    <measurement group_id="O2" value="88.3" lower_limit="81.5" upper_limit="94.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>30 minutes post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.2" lower_limit="74.5" upper_limit="89.7"/>
                    <measurement group_id="O2" value="73.9" lower_limit="42.6" upper_limit="87.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>1 hour post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.2" lower_limit="34.1" upper_limit="87.2"/>
                    <measurement group_id="O2" value="42.0" lower_limit="25.6" upper_limit="81.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>2 hours post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.1" lower_limit="21.7" upper_limit="80.5"/>
                    <measurement group_id="O2" value="26.2" lower_limit="18.7" upper_limit="52.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>3 hours post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.8" lower_limit="24.7" upper_limit="75.1"/>
                    <measurement group_id="O2" value="26.0" lower_limit="13.1" upper_limit="52.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>4 hours post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.9" lower_limit="19.1" upper_limit="64.1"/>
                    <measurement group_id="O2" value="23.2" lower_limit="14.3" upper_limit="43.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>6 hours post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.9" lower_limit="18.2" upper_limit="44.1"/>
                    <measurement group_id="O2" value="19.7" lower_limit="12.7" upper_limit="33.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Reactivity Index Assessed by VASP Assay</title>
        <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
        <time_frame>12 hours post ticagrelor dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Reactivity Index Assessed by VASP Assay</title>
          <description>Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI &gt;50%)</description>
          <units>Platelet Reactivity Index (%)</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.5" lower_limit="17.0" upper_limit="42.3"/>
                    <measurement group_id="O2" value="15.6" lower_limit="12.3" upper_limit="33.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>prior to the initial ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85" lower_limit="70" upper_limit="102"/>
                    <measurement group_id="O2" value="77" lower_limit="54" upper_limit="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>30 minutes post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86" lower_limit="53" upper_limit="99"/>
                    <measurement group_id="O2" value="48" lower_limit="22" upper_limit="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>1 hour post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59" lower_limit="31" upper_limit="86"/>
                    <measurement group_id="O2" value="23" lower_limit="17" upper_limit="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>2 hours post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31" lower_limit="20" upper_limit="71"/>
                    <measurement group_id="O2" value="23" lower_limit="10" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>3 hours post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27" lower_limit="18" upper_limit="55"/>
                    <measurement group_id="O2" value="17" lower_limit="10" upper_limit="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>4 hours post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29" lower_limit="10" upper_limit="44"/>
                    <measurement group_id="O2" value="13" lower_limit="9" upper_limit="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>6 hours post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19" lower_limit="9" upper_limit="34"/>
                    <measurement group_id="O2" value="11" lower_limit="5" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
        <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
        <time_frame>12 hours post ticagrelor dose</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry</title>
          <description>Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC &gt;46 Platelet Arbitrary Aggregation Units)</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Platelet Arbitrary Aggregation Units</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19" lower_limit="10" upper_limit="27"/>
                    <measurement group_id="O2" value="11" lower_limit="7" upper_limit="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>prior to the initial ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="232.5" lower_limit="197.0" upper_limit="270.0"/>
                    <measurement group_id="O2" value="238.5" lower_limit="194.0" upper_limit="267.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>30 minutes post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="268.5" lower_limit="202.0" upper_limit="299.0"/>
                    <measurement group_id="O2" value="210.5" lower_limit="118.0" upper_limit="266.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>1 hour post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="206.5" lower_limit="88.0" upper_limit="266.0"/>
                    <measurement group_id="O2" value="117.0" lower_limit="10.0" upper_limit="233.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>2 hours post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="137.0" lower_limit="27.0" upper_limit="251.0"/>
                    <measurement group_id="O2" value="44.0" lower_limit="7.0" upper_limit="119.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>3 hours post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.0" lower_limit="31.0" upper_limit="221.0"/>
                    <measurement group_id="O2" value="15.0" lower_limit="4.0" upper_limit="52.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>4 hours post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.5" lower_limit="8.0" upper_limit="165.0"/>
                    <measurement group_id="O2" value="9.0" lower_limit="4.0" upper_limit="72.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>6 hours post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.5" lower_limit="6.0" upper_limit="171.0"/>
                    <measurement group_id="O2" value="8.0" lower_limit="3.0" upper_limit="21.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
        <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
        <time_frame>12 hours post ticagrelor dose</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>P2Y12 Reaction Units Assessed by VerifyNow</title>
          <description>P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU &gt;208)</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>P2Y12 Reaction Units</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" lower_limit="4.0" upper_limit="116.0"/>
                    <measurement group_id="O2" value="7.5" lower_limit="3.0" upper_limit="48.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP</title>
        <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP</description>
        <time_frame>2 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP</title>
          <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP</description>
          <units>Percentage of Patients With HPR</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA</title>
        <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA</description>
        <time_frame>2 hours</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA</title>
          <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>Percentage of Patients With HPR</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow</title>
        <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow</description>
        <time_frame>2 hours</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow</title>
          <description>Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>Percentage of Patients With HPR</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP</title>
        <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP</description>
        <time_frame>12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP</title>
          <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP</description>
          <units>hours</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="1.0" upper_limit="6.0"/>
                    <measurement group_id="O2" value="1" lower_limit="0.5" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA</title>
        <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA</description>
        <time_frame>12 hours</time_frame>
        <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA</title>
          <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA</description>
          <population>According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.</population>
          <units>hours</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="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="1.0" upper_limit="4.0"/>
                    <measurement group_id="O2" value="1.0" lower_limit="0.5" upper_limit="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow</title>
        <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow</description>
        <time_frame>12 hours</time_frame>
        <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow</title>
          <description>Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow</description>
          <population>In line with the study protocol, VerifyNow pharmacodynamic evaluation involved &gt;30% of the overall study population.</population>
          <units>hours</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="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0" upper_limit="3.0"/>
                    <measurement group_id="O2" value="0.5" lower_limit="0" upper_limit="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>7 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Morphine</title>
          <description>morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Morphine: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor&#xD;
Placebo: IV bolus injection&#xD;
Ticagrelor: 180 mg loading dose</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Stent thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradyarrhythmic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>TIMI minor bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>TIMI minimal bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </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. Jacek Kubica</name_or_title>
      <organization>Collegium Medicum, Nicolaus Copernicus University</organization>
      <phone>+485854023</phone>
      <email>jkubica@cm.umk.pl</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/NCT02217878
org study id: CMUMK202
nct id: NCT02217878
lead sponsor: 
has dmc: No
The purpose of the IMPRESSION study is to determine whether intravenous administration of
      morphine prior to ticagrelor administration in ST-segment elevation myocardial infarction
      (STEMI) patients and in non-ST-segment elevation myocardial infarction (NSTEMI) patients
      alters the plasma concentrations of ticagrelor and its active metabolite and whether it is
      associated with any negative impact on the antiplatelet effect of ticagrelor.
The European Society of Cardiology and American Heart Association guidelines recommend use of
      morphine as a treatment of choice for pain relief in STEMI patients. However, this
      recommendation, although strong, is only based on expert consensus (class of recommendation
      I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the work
      of breathing and reduces anxiety. On the other hand, despite its favorable analgesic and
      sedative actions, morphine also exerts adverse effects, which include hypotension,
      bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility.
      Some of the previously listed morphine's side effects could affect the intestinal absorption
      and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are
      concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data
      regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting
      are available. Therefore, evidence-based verification of morphine's influence on
      pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX)
      could provide a valuable insight in the knowledge regarding modern acute myocardial
      infarction management.

      Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment
      methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration
      of ticagrelor and its active metabolite (AR-C124910XX).

      Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or NSTEMI
      patients, we decided to perform an internal pilot study of approximately 30 patients (15
      patients for each arm) for estimating the final sample size.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
time frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
description: Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose
measure: Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
time frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
description: Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose
measure: Maximum Concentration of Ticagrelor
time frame: 12 hours
description: Maximum concentration (Cmax) of ticagrelor
measure: Maximum Concentration of AR-C124910XX
time frame: 12 hours
description: Maximum concentration (Cmax) of AR-C124910XX
measure: Time to Maximum Concentration for Ticagrelor
time frame: 12 hours
description: Time to maximum concentration (Tmax) for ticagrelor
measure: Time to Maximum Concentration for AR-C124910XX
time frame: 12 hours
description: Time to maximum concentration (Tmax) for AR-C124910XX
measure: Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
time frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
description: Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose
measure: Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)
time frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
description: Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: prior to the initial ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 30 minutes post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 1 hour post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 2 hours post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 3 hours post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 4 hours post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 6 hours post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Reactivity Index Assessed by VASP Assay
time frame: 12 hours post ticagrelor dose
description: Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: prior to the initial ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 30 minutes post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 1 hour post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 2 hours post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 3 hours post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 4 hours post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 6 hours post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
time frame: 12 hours post ticagrelor dose
description: Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: prior to the initial ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 30 minutes post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 1 hour post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 2 hours post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 3 hours post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 4 hours post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 6 hours post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: P2Y12 Reaction Units Assessed by VerifyNow
time frame: 12 hours post ticagrelor dose
description: P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
measure: Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
time frame: 2 hours
description: Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP
measure: Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA
time frame: 2 hours
description: Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
measure: Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
time frame: 2 hours
description: Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow
measure: Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP
time frame: 12 hours
description: Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
measure: Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
time frame: 12 hours
description: Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
measure: Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
time frame: 12 hours
description: Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
arm group label: Morphine
arm group type: Active Comparator
description: morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
arm group label: Placebo
arm group type: Placebo Comparator
description: sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
intervention type: Drug
intervention name: Morphine
description: IV bolus injection
arm group label: Morphine
other name: Morphine sulfate
intervention type: Drug
intervention name: Placebo
description: IV bolus injection
arm group label: Placebo
other name: Sodium chloride 0,9%
intervention type: Drug
intervention name: Ticagrelor
description: 180 mg loading dose
arm group label: Morphine
arm group label: Placebo
other name: Brilique
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Prof. Jacek Kubica, MD, PhD
role: Principal Investigator
affiliation: Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
facility: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Collegium Medicum w Bydgoszczy
investigator full name: Jacek Kubica
investigator title: Prof. dr hab.
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: Morphine
mesh term: Ticagrelor
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 