<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/NCT04483583</url>
  </required_header>
  <id_info>
    <org_study_id>IRB202001360</org_study_id>
    <nct_id>NCT04483583</nct_id>
  </id_info>
  <brief_title>Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI</brief_title>
  <acronym>SWAP-AC-2</acronym>
  <official_title>Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After Undergoing Percutaneous Coronary Intervention:The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) - 2 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clopidogrel is the P2Y12 inhibitor of choice in PCI patients requiring OAC. However, concerns&#xD;
      have been raised based on the notion that a considerable number of patients may have&#xD;
      inadequate response to clopidogrel. Although practice recommendations indicate that the use&#xD;
      of potent P2Y12 inhibitors (i.e., ticagrelor) may be considered in patients at increased&#xD;
      thrombotic risk, they do not recommend routine testing to identify patients with poor&#xD;
      response to clopidogrel. The aim of this study is to assess the pharmacodynamic effects of&#xD;
      different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in patients at high risk for&#xD;
      high platelet reactivity identified according to the ABCD-GENE score in PCI treated patients&#xD;
      also requiring OAC. Up to a total of up to 63 patients are planned to be prospectively&#xD;
      enrolled in this investigation which will entail a series of comprehensive pharmacodynamic&#xD;
      assessments to reach the study aim.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The combination of aspirin plus a P2Y12 receptor inhibitor, also known as dual antiplatelet&#xD;
      therapy (DAPT), is the cornerstone of treatment for patients with coronary artery disease&#xD;
      (CAD) undergoing percutaneous coronary intervention (PCI). However, a considerable number of&#xD;
      patients undergoing PCI also have an indication to be on treatment with an oral anticoagulant&#xD;
      (OAC). It is estimated that 10-15% of PCI patients also have an indication to be on OAC,&#xD;
      raising concerns on their optimal antithrombotic treatment regimen. Studies have consistently&#xD;
      shown dropping aspirin and maintaining a P2Y12 inhibitor and OAC to be associated with&#xD;
      reduces bleeding without any significant increase in ischemic events. Accordingly, current&#xD;
      practice recommendations is to limit the use of aspirin to the peri-PCI period and maintain&#xD;
      dual therapy with a P2Y12 inhibitor and an OAC. Clopidogrel is the P2Y12 inhibitor of choice&#xD;
      in PCI patients requiring OAC. However, concerns have been raised based on the notion that a&#xD;
      considerable number of patients may have inadequate response to clopidogrel, also known as&#xD;
      high platelet reactivity (HPR) status, and thus be at risk for thrombotic complications.&#xD;
      Although practice recommendations indicate that the use of potent P2Y12 inhibitors (i.e.,&#xD;
      ticagrelor) may be considered in patients at increased thrombotic risk, they do not recommend&#xD;
      routine testing to identify patients with HPR status. Nevertheless, consensus recommendations&#xD;
      do indicate that the selective use of tests to define HPR status is a reasonable option in&#xD;
      selected cases such as PCI patients requiring OAC. The aim of this study is to assess the&#xD;
      pharmacodynamic effects of different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in&#xD;
      patients at high risk for HPR identified according to the ABCD-GENE score in PCI treated&#xD;
      patients also requiring OAC. Up to a total of up to 63 patients are planned to be&#xD;
      prospectively enrolled in this investigation which will entail a series of comprehensive&#xD;
      pharmacodynamic assessments to reach the study aim.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 8, 2020</start_date>
  <completion_date type="Anticipated">May 4, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 4, 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Platelet reactivity measured as PRU</measure>
    <time_frame>30 days</time_frame>
    <description>The primary end point of our study will be levels of platelet reactivity, measured as P2Y12 reaction units (PRU) using the VerifyNow system of ticagrelor versus clopidogrel in patients with an ABCD-Gene score ≥10.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>ABCD-GENE &gt;10 - Clopidogrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with an ABCD-GENE&gt;10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ABCD-GENE &gt;10 - Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with an ABCD-GENE&gt;10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ABCD-GENE &lt;10 - Clopidogrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with an ABCD-GENE&lt;10 will be treated with clopidogrel (75 mg/qd) for 30 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor 60mg</intervention_name>
    <description>Patients will be administered a 180 mg loading dose followed by a 60 mg bid for the duration of the study.</description>
    <arm_group_label>ABCD-GENE &gt;10 - Ticagrelor</arm_group_label>
    <other_name>brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <description>Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.</description>
    <arm_group_label>ABCD-GENE &lt;10 - Clopidogrel</arm_group_label>
    <arm_group_label>ABCD-GENE &gt;10 - Clopidogrel</arm_group_label>
    <other_name>plavix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
          -  Undergone successful PCI and treated with DAPT (aspirin plus a P2Y12 inhibitor) per&#xD;
             standard of care&#xD;
&#xD;
          -  On treatment with a novel oral anticoagulant (apixaban, dabigatran, edoxaban, or&#xD;
             rivaroxaban) for any indication (dosing regimen will be according to standard of care&#xD;
             and at the discretion of the treating physician)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Any active bleeding or history of major bleeding&#xD;
&#xD;
          -  Ischemic Stroke within 1 month&#xD;
&#xD;
          -  Any history of hemorrhagic stroke, or intracranial hemorrhage&#xD;
&#xD;
          -  Known non-cardiovascular disease that is associated with poor prognosis (e.g.,&#xD;
             metastatic cancer) or that increases the risk of an adverse reaction to study&#xD;
             interventions.&#xD;
&#xD;
          -  End-stage renal disease on hemodialysis&#xD;
&#xD;
          -  Known severe liver dysfunction or any known hepatic disease associated with&#xD;
             coagulopathy&#xD;
&#xD;
          -  History of hypersensitivity or known contraindication to clopidogrel or ticagrelor.&#xD;
&#xD;
          -  Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (e.g.,&#xD;
             systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus&#xD;
             [HIV]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e.&#xD;
&#xD;
        rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine&#xD;
&#xD;
          -  Subjects who are pregnant, breastfeeding, or are of childbearing potential, and&#xD;
             sexually active and not practicing an effective method of birth control (e.g.&#xD;
             surgically sterile, prescription oral contraceptives, contraceptive injections,&#xD;
             intrauterine device, double barrier method, contraceptive patch, male partner&#xD;
             sterilization)&#xD;
&#xD;
          -  Concomitant participation in another study with investigational drug&#xD;
&#xD;
          -  Hemoglobin ≤9 mg/dL&#xD;
&#xD;
          -  Platelet count &lt;80x106/mL&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dominick J Angiolillo, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dominick J Angiolillo, MD, PhD</last_name>
    <phone>9042443378</phone>
    <email>dominick.angiolillo@jax.ufl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Francesco Franchi</last_name>
    <phone>904-244-2060</phone>
    <email>francesco.franchi@jax.ufl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dominick J Angiolillo, MD, PhD</last_name>
      <email>dominick.angiolillo@jax.ufl.edu</email>
    </contact>
    <investigator>
      <last_name>Dominick J Angiolillo, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>June 5, 2023</last_update_submitted>
  <last_update_submitted_qc>June 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>percutaneous coronary intervention</keyword>
  <keyword>dual antiplatelet therapy</keyword>
  <keyword>oral anticoagulant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clopidogrel</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04483583
org study id: IRB202001360
nct id: NCT04483583
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Clopidogrel is the P2Y12 inhibitor of choice in PCI patients requiring OAC. However, concerns
      have been raised based on the notion that a considerable number of patients may have
      inadequate response to clopidogrel. Although practice recommendations indicate that the use
      of potent P2Y12 inhibitors (i.e., ticagrelor) may be considered in patients at increased
      thrombotic risk, they do not recommend routine testing to identify patients with poor
      response to clopidogrel. The aim of this study is to assess the pharmacodynamic effects of
      different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in patients at high risk for
      high platelet reactivity identified according to the ABCD-GENE score in PCI treated patients
      also requiring OAC. Up to a total of up to 63 patients are planned to be prospectively
      enrolled in this investigation which will entail a series of comprehensive pharmacodynamic
      assessments to reach the study aim.
The combination of aspirin plus a P2Y12 receptor inhibitor, also known as dual antiplatelet
      therapy (DAPT), is the cornerstone of treatment for patients with coronary artery disease
      (CAD) undergoing percutaneous coronary intervention (PCI). However, a considerable number of
      patients undergoing PCI also have an indication to be on treatment with an oral anticoagulant
      (OAC). It is estimated that 10-15% of PCI patients also have an indication to be on OAC,
      raising concerns on their optimal antithrombotic treatment regimen. Studies have consistently
      shown dropping aspirin and maintaining a P2Y12 inhibitor and OAC to be associated with
      reduces bleeding without any significant increase in ischemic events. Accordingly, current
      practice recommendations is to limit the use of aspirin to the peri-PCI period and maintain
      dual therapy with a P2Y12 inhibitor and an OAC. Clopidogrel is the P2Y12 inhibitor of choice
      in PCI patients requiring OAC. However, concerns have been raised based on the notion that a
      considerable number of patients may have inadequate response to clopidogrel, also known as
      high platelet reactivity (HPR) status, and thus be at risk for thrombotic complications.
      Although practice recommendations indicate that the use of potent P2Y12 inhibitors (i.e.,
      ticagrelor) may be considered in patients at increased thrombotic risk, they do not recommend
      routine testing to identify patients with HPR status. Nevertheless, consensus recommendations
      do indicate that the selective use of tests to define HPR status is a reasonable option in
      selected cases such as PCI patients requiring OAC. The aim of this study is to assess the
      pharmacodynamic effects of different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in
      patients at high risk for HPR identified according to the ABCD-GENE score in PCI treated
      patients also requiring OAC. Up to a total of up to 63 patients are planned to be
      prospectively enrolled in this investigation which will entail a series of comprehensive
      pharmacodynamic assessments to reach the study aim.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Platelet reactivity measured as PRU
time frame: 30 days
description: The primary end point of our study will be levels of platelet reactivity, measured as P2Y12 reaction units (PRU) using the VerifyNow system of ticagrelor versus clopidogrel in patients with an ABCD-Gene score ≥10.
arm group label: ABCD-GENE >10 - Clopidogrel
arm group type: Active Comparator
description: Patients with an ABCD-GENE>10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days.
arm group label: ABCD-GENE >10 - Ticagrelor
arm group type: Experimental
description: Patients with an ABCD-GENE>10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days.
arm group label: ABCD-GENE <10 - Clopidogrel
arm group type: Active Comparator
description: Patients with an ABCD-GENE<10 will be treated with clopidogrel (75 mg/qd) for 30 days.
intervention type: Drug
intervention name: Ticagrelor 60mg
description: Patients will be administered a 180 mg loading dose followed by a 60 mg bid for the duration of the study.
arm group label: ABCD-GENE >10 - Ticagrelor
other name: brilinta
intervention type: Drug
intervention name: Clopidogrel
description: Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.
arm group label: ABCD-GENE <10 - Clopidogrel
arm group label: ABCD-GENE >10 - Clopidogrel
other name: plavix
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dominick J Angiolillo, MD, PhD
role: Principal Investigator
affiliation: University of Florida
last name: Dominick J Angiolillo, MD, PhD
phone: 9042443378
email: dominick.angiolillo@jax.ufl.edu
last name: Francesco Franchi
phone: 904-244-2060
email: francesco.franchi@jax.ufl.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Clopidogrel
mesh term: Ticagrelor
sharing ipd: No