<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/NCT03296540</url>
  </required_header>
  <id_info>
    <org_study_id>2017-40</org_study_id>
    <nct_id>NCT03296540</nct_id>
  </id_info>
  <brief_title>CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI</brief_title>
  <acronym>CompareCrush</acronym>
  <official_title>COMPARison of Pre-hospital CRUSHed vs. Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maasstad Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MicroPort Orthopedics Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Maatschap Cardiologen Rotterdam Zuid</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maasstad Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The studys evaluates the effect of prehospital administration of crushed tablets of Prasugrel&#xD;
      loading dose (in addition to ASA and standard care) versus uncrushed tablets of Prasugrel&#xD;
      loading dose on efficacy and safety as well as pharmacodynamics as measured by platelet&#xD;
      reactivity using VerifyNow.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a two-centre, randomized, 1:1 trial comparing prehospital prasugrel initiation&#xD;
      therapy between crushed vs. uncrushed prasugrel tablets on efficacy and safety as well as&#xD;
      pharmacodynamics in STEMI patients.&#xD;
&#xD;
      Patients with STEMI planned for primary PCI will be screened and, if inclusion criteria are&#xD;
      met, included at first medical contact (paramedics). After enrolment, patients will be&#xD;
      randomly assigned (1:1) to receive 60mg prasugrel loading dose by ingesting integral or&#xD;
      crushed tablets.&#xD;
&#xD;
      The follow-up duration is 12 months, i.e. clinical outcomes will be analysed in-hospital, at&#xD;
      30 days, and 12 months&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Actual">May 1, 2021</completion_date>
  <primary_completion_date type="Actual">May 1, 2021</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>
    <intervention_model_description>Crushed versus uncrushed tablets Prasugrel loading dose</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Co-primary endpoint is the percentage of patients reaching TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment resolution directly post-PCI</measure>
    <time_frame>directly post PCI</time_frame>
    <description>To assess the efficacy of crushed vs. integral tablets of prasugrel loading dose treatment by comparing the percentage of patients reaching the co-primary endpoint of TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment elevation resolution directly post-PCI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months</measure>
    <time_frame>upto 72 hours after randomisation, at 30 days and 12 months.</time_frame>
    <description>Percentage of patients in the following: composite of death, MI, stroke, urgent revascularization and acute stent thrombosis during inhospital stay, 30 days and 12 months of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study</measure>
    <time_frame>30 days and 12 months</time_frame>
    <description>Percentage of patients in the following: composite of death, MI, or urgent revascularization during inhospital, 30 days and 12 months of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual endpoints during inhospital, at 30 days and 12 months of study</measure>
    <time_frame>upto 72 hours after randomisation, at 30 days and 12 months.</time_frame>
    <description>Percentage of patients presenting with any of the individual endpoints during inhospital, 30 days and 12 months of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI</measure>
    <time_frame>directly post PCI</time_frame>
    <description>Percentage of patients receiving thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI</measure>
    <time_frame>pre-PCI and 60 min post-PCI</time_frame>
    <description>Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.</measure>
    <time_frame>pre PCI, directly post PCI</time_frame>
    <description>Corrected TIMI frame count (cTFC) at angiography, pre and post PCI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.</measure>
    <time_frame>pre PCI, directly post PCI</time_frame>
    <description>TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-relationship (from symptom onset to 1st dose intake) on each co-primary</measure>
    <time_frame>directly post-PCI</time_frame>
    <description>Time from symptom onset to 1st dose intake correlated to TIMI flow grade 3 of MI culprit vessel at initial angiography and on ≥70% ST-segment elevation resolution directly post-PCI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary</measure>
    <time_frame>directly post-PCI</time_frame>
    <description>Time from first dose intake to ECG correlated to ≥70% ST-segment elevation resolution directly post-PCI and time from randomization to initial angiography correlated to TIMI flow grade 3 of MI culprit vessel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TIMI flow grade 3 at end of procedure.</measure>
    <time_frame>directly post PCI</time_frame>
    <description>TIMI flow grade 3 at end of procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial Blush at the start and end of the procedure</measure>
    <time_frame>pre PCI, directly post PCI</time_frame>
    <description>Myocardial Blush at the start and end of the procedure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum CK, and CK-MB levels</measure>
    <time_frame>upto 72 hours after randomisation</time_frame>
    <description>Maximum CK, and CK-MB levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration</measure>
    <time_frame>at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration</time_frame>
    <description>Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet reactivity, at each time point as well as over time</measure>
    <time_frame>at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration</time_frame>
    <description>PRU measurements at first medical contact, beginning and end of PCI, as well as 4hours after drug administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of HPR</measure>
    <time_frame>upto 72 hours after randomisation</time_frame>
    <description>Percentage of patients with PRU values over HPR threshold</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory analyses within each group to evaluate any differences in PD among patients receiving morphine</measure>
    <time_frame>upto 72 hours after randomisation</time_frame>
    <description>PD of each group among patients stratified for morphine treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">729</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Uncrushed</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>6 Integral tablets Prasugrel as loading dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Crushed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Crushed tablets Prasugrel as loading dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prasugrel (Crushed tablets)</intervention_name>
    <description>loading dose of 6 crushed tablets 10mg Prasugrel</description>
    <arm_group_label>Crushed</arm_group_label>
    <other_name>6 Crushed tablets of Prasugrel 10mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prasugrel (Integral tablets)</intervention_name>
    <description>loading dose of 6 integral tablets of 10mg Prasugrel</description>
    <arm_group_label>Uncrushed</arm_group_label>
    <other_name>6 Integral tablets of Prasugrel 10mg</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Consecutive patients with STEMI planned for primary PCI:&#xD;
&#xD;
          -  Deferred written informed consent within 4 hours after prasugrel loading dose&#xD;
&#xD;
          -  Adult men and women aged at least 18 years&#xD;
&#xD;
          -  Symptoms of acute MI of more than 30 min but less than 6 hours&#xD;
&#xD;
          -  New persistent ST-segment elevation ≥ 1 mm in two or more contiguous ECG leads&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to prasugrel (e.g., hypersensitivity, active bleeding, history of&#xD;
             previous intracranial bleed, history of any CVA including TIA, moderate to severe&#xD;
             hepatic impairment, GI bleed within the past 6 months, major surgery within past 4&#xD;
             weeks)&#xD;
&#xD;
          -  Patient who has received loading dose of clopidogrel or ticagrelor for the index event&#xD;
             or are on chronic treatment of ticagrelor, or prasugrel. However, patients on&#xD;
             maintenance dose clopidogrel for at least 7 days are included in the study (see&#xD;
             appendix A).&#xD;
&#xD;
          -  Oral anticoagulation therapy that cannot be stopped (i.e. patients requiring chronic&#xD;
             therapy)&#xD;
&#xD;
          -  Planned fibrinolytic treatment&#xD;
&#xD;
          -  Patient requiring dialysis&#xD;
&#xD;
          -  Known, clinically important thrombocytopenia&#xD;
&#xD;
          -  Known clinically important anaemia&#xD;
&#xD;
          -  Known pregnancy or lactation&#xD;
&#xD;
          -  Need for a concomitant systemic therapy with strong inhibitors or strong inducers of&#xD;
             CYP3A&#xD;
&#xD;
          -  Condition which may either put the patient at risk or influence the result of the&#xD;
             study (e.g., cardiogenic shock with severe hemodynamic instability, active cancer,&#xD;
             risk for non-compliance, risk for being lost to follow up)&#xD;
&#xD;
          -  Patient unable to swallow oral medication (i.e. intubated patients)&#xD;
&#xD;
          -  Patient who have not received prasugrel loading dose in the ambulance&#xD;
&#xD;
          -  Patient who vomited after randomization / receiving the loading dose prasugrel&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>George Vlachojannis, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maasstadziekenhuis</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pieter C Smits, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Maasstadziekenhuis</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicolas van Mieghem, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Erasmus Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Erasmus Medical Center</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maasstadziekenhuis</name>
      <address>
        <city>Rotterdam</city>
        <zip>3079 DZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>September 6, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>May 6, 2021</last_update_submitted>
  <last_update_submitted_qc>May 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>STEMI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prasugrel Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 6, 2022</submitted>
    <returned>July 27, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03296540
org study id: 2017-40
nct id: NCT03296540
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The studys evaluates the effect of prehospital administration of crushed tablets of Prasugrel
      loading dose (in addition to ASA and standard care) versus uncrushed tablets of Prasugrel
      loading dose on efficacy and safety as well as pharmacodynamics as measured by platelet
      reactivity using VerifyNow.
The study is a two-centre, randomized, 1:1 trial comparing prehospital prasugrel initiation
      therapy between crushed vs. uncrushed prasugrel tablets on efficacy and safety as well as
      pharmacodynamics in STEMI patients.

      Patients with STEMI planned for primary PCI will be screened and, if inclusion criteria are
      met, included at first medical contact (paramedics). After enrolment, patients will be
      randomly assigned (1:1) to receive 60mg prasugrel loading dose by ingesting integral or
      crushed tablets.

      The follow-up duration is 12 months, i.e. clinical outcomes will be analysed in-hospital, at
      30 days, and 12 months
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Crushed versus uncrushed tablets Prasugrel loading dose
primary purpose: Treatment
masking: None (Open Label)
measure: Co-primary endpoint is the percentage of patients reaching TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment resolution directly post-PCI
time frame: directly post PCI
description: To assess the efficacy of crushed vs. integral tablets of prasugrel loading dose treatment by comparing the percentage of patients reaching the co-primary endpoint of TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment elevation resolution directly post-PCI.
measure: Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months
time frame: upto 72 hours after randomisation, at 30 days and 12 months.
description: Percentage of patients in the following: composite of death, MI, stroke, urgent revascularization and acute stent thrombosis during inhospital stay, 30 days and 12 months of study
measure: Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study
time frame: 30 days and 12 months
description: Percentage of patients in the following: composite of death, MI, or urgent revascularization during inhospital, 30 days and 12 months of study
measure: Individual endpoints during inhospital, at 30 days and 12 months of study
time frame: upto 72 hours after randomisation, at 30 days and 12 months.
description: Percentage of patients presenting with any of the individual endpoints during inhospital, 30 days and 12 months of study
measure: Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
time frame: directly post PCI
description: Percentage of patients receiving thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
measure: Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI
time frame: pre-PCI and 60 min post-PCI
description: Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI
measure: Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.
time frame: pre PCI, directly post PCI
description: Corrected TIMI frame count (cTFC) at angiography, pre and post PCI
measure: TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.
time frame: pre PCI, directly post PCI
description: TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.
measure: Time-relationship (from symptom onset to 1st dose intake) on each co-primary
time frame: directly post-PCI
description: Time from symptom onset to 1st dose intake correlated to TIMI flow grade 3 of MI culprit vessel at initial angiography and on ≥70% ST-segment elevation resolution directly post-PCI
measure: Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary
time frame: directly post-PCI
description: Time from first dose intake to ECG correlated to ≥70% ST-segment elevation resolution directly post-PCI and time from randomization to initial angiography correlated to TIMI flow grade 3 of MI culprit vessel
measure: TIMI flow grade 3 at end of procedure.
time frame: directly post PCI
description: TIMI flow grade 3 at end of procedure.
measure: Myocardial Blush at the start and end of the procedure
time frame: pre PCI, directly post PCI
description: Myocardial Blush at the start and end of the procedure
measure: Maximum CK, and CK-MB levels
time frame: upto 72 hours after randomisation
description: Maximum CK, and CK-MB levels
measure: Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration
time frame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
description: Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration
measure: Platelet reactivity, at each time point as well as over time
time frame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
description: PRU measurements at first medical contact, beginning and end of PCI, as well as 4hours after drug administration
measure: Rates of HPR
time frame: upto 72 hours after randomisation
description: Percentage of patients with PRU values over HPR threshold
measure: Exploratory analyses within each group to evaluate any differences in PD among patients receiving morphine
time frame: upto 72 hours after randomisation
description: PD of each group among patients stratified for morphine treatment
arm group label: Uncrushed
arm group type: Active Comparator
description: 6 Integral tablets Prasugrel as loading dose
arm group label: Crushed
arm group type: Experimental
description: 6 Crushed tablets Prasugrel as loading dose
intervention type: Drug
intervention name: Prasugrel (Crushed tablets)
description: loading dose of 6 crushed tablets 10mg Prasugrel
arm group label: Crushed
other name: 6 Crushed tablets of Prasugrel 10mg
intervention type: Drug
intervention name: Prasugrel (Integral tablets)
description: loading dose of 6 integral tablets of 10mg Prasugrel
arm group label: Uncrushed
other name: 6 Integral tablets of Prasugrel 10mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: George Vlachojannis, MD, PhD
role: Principal Investigator
affiliation: Maasstadziekenhuis
last name: Pieter C Smits, MD, PhD
role: Study Director
affiliation: Maasstadziekenhuis
last name: Nicolas van Mieghem, MD, PhD
role: Study Chair
affiliation: Erasmus Medical Center
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Prasugrel Hydrochloride
sharing ipd: No
submitted: September 6, 2022
returned: July 27, 2023