<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/NCT04484259</url>
  </required_header>
  <id_info>
    <org_study_id>IRB202001694</org_study_id>
    <nct_id>NCT04484259</nct_id>
  </id_info>
  <brief_title>Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus</brief_title>
  <acronym>OPTIMUS-7</acronym>
  <official_title>Pharmacodynamic Effects of Different Ticagrelor Maintenance Dosing Regimens With and Without Aspirin in Patients With Diabetes Mellitus: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-7 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent studies have shown that withdrawing aspirin and maintaining P2Y12 inhibitor&#xD;
      monotherapy for up to 12 months post-PCI, after a brief period of DAPT, reduces bleeding&#xD;
      without increasing ischemic harm. Such effects have shown to of particular benefit in&#xD;
      patients with diabetes mellitus (DM). However, if an aspirin-free approach can be considered&#xD;
      after this time frame is a matter of debate. The aim of this study is to assess the PD&#xD;
      effects of ticagrelor 60 mg with and without aspirin therapy in CAD patients and to compare&#xD;
      this with a standard DAPT regimen of aspirin plus clopidogrel.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care&#xD;
      for the prevention of thrombotic complications in patients with coronary artery disease (CAD)&#xD;
      undergoing percutaneous coronary interventions (PCI). However, such ischemic benefit occurs&#xD;
      at the expense of enhanced bleeding, the risk of which increases in a graded fashion with&#xD;
      prolonged exposure to DAPT. Recent studies have shown that withdrawing aspirin and&#xD;
      maintaining P2Y12 inhibitor monotherapy for up to 12 months post-PCI, after a brief period of&#xD;
      DAPT, reduces bleeding without increasing ischemic harm. Such effects have shown to of&#xD;
      particular benefit in patients with diabetes mellitus (DM). However, if an aspirin-free&#xD;
      approach can be considered after this time frame is a matter of debate. In fact, current&#xD;
      guidelines recommend maintaining P2Y12 inhibiting therapy for high risk patients but which&#xD;
      all imply background use of aspirin. P2Y12 inhibitors for long-term (beyond 12 months)&#xD;
      secondary prevention mainly include clopidogrel and ticagrelor. In particular, the dosing&#xD;
      regimen for clopidogrel remains the standard 75 mg qd, whereas ticagrelor dosing is&#xD;
      recommended to be reduced from 90 mg bid to 60 mg bid. However, of these regimens the&#xD;
      pharmacodynamics (PD) effects of ticagrelor 60 mg in the absence of aspirin has not yet been&#xD;
      tested. Because DM patients are likely to continue with long-term P2Y12 inhibitor therapy,&#xD;
      defining the optimal antithrombotic approach for these patients is of critical importance. In&#xD;
      light of the above made observations, patients with DM represent an ideal population to&#xD;
      define the antiplatelet effects of a ticagrelor 60 mg monotherapy regimen. The aim of this&#xD;
      study is to assess the PD effects of ticagrelor 60 mg with and without aspirin therapy in CAD&#xD;
      patients and to compare this with a standard DAPT regimen of aspirin plus clopidogrel.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 31, 2021</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">May 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>
    <intervention_model_description>Prospective randomized</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Staff performing PK/PD assessments will remain blinded to treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>P2Y12 reaction units (PRU)</measure>
    <time_frame>10 days</time_frame>
    <description>The primary end-point of the study is the comparison of the PRU determined by VerifyNow PRU between between aspirin plus ticagrelor 60 mg and ticagrelor 60 mg monotherapy (trough effect pre-dosing)</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">63</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ticagrelor 60 mg bid monotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin plus Clopidogrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>aspirin 81 mg qd plus clopidogrel 75 mg qd</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin plus Ticagrelor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>aspirin 81 mg qd plus ticagrelor 60 mg bid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor monotherapy</intervention_name>
    <description>Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.</description>
    <arm_group_label>Ticagrelor</arm_group_label>
    <other_name>Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor plus aspirin</intervention_name>
    <description>Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.</description>
    <arm_group_label>Aspirin plus Ticagrelor</arm_group_label>
    <other_name>Brilinta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel with aspirin</intervention_name>
    <description>Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.</description>
    <arm_group_label>Aspirin plus Clopidogrel</arm_group_label>
    <other_name>Plavix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        For inclusion in the study patients should fulfill the following criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures&#xD;
&#xD;
          2. Men or women ≥18 years of age&#xD;
&#xD;
          3. Diagnosed with type 2 DM defined by ongoing glucose lowering therapy (oral medications&#xD;
             and/or insulin) treatment for at least 1 month&#xD;
&#xD;
          4. Known CAD with a history of previous PCI on standard of care antiplatelet therapy*&#xD;
             *Patients can be treated with any background antiplatelet treatment regimen as part of&#xD;
             their standard of care, including aspirin and/or any P2Y12 inhibitor (clopidogrel,&#xD;
             ticagrelor, prasugrel).&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. PCI &lt; 6 months prior&#xD;
&#xD;
          2. Recent (&lt; 6 months) type I myocardial infarction&#xD;
&#xD;
          3. Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4&#xD;
             (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot&#xD;
             be stopped for the course of the study:&#xD;
&#xD;
               -  Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin,&#xD;
                  clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir,&#xD;
                  saquinavir, nelfinavir, indinavir, atanazavir&#xD;
&#xD;
               -  CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses&#xD;
                  &gt;40 mg daily or lovastatin at doses &gt;40 mg daily&#xD;
&#xD;
          4. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin&#xD;
             (at venous thrombosis treatment not prophylaxis doses)&#xD;
&#xD;
          5. Patients with known bleeding diathesis or coagulation disorder&#xD;
&#xD;
          6. History of previous intracerebral bleed at any time, gastrointestinal (GI) bleed&#xD;
             within the past 6 months prior to randomization, or major surgery within 30 days prior&#xD;
             to randomization&#xD;
&#xD;
          7. Active pathological bleeding&#xD;
&#xD;
          8. Hypersensitivity to aspirin, ticagrelor or clopidogrel&#xD;
&#xD;
          9. Increased risk of bradycardic events (eg, known sick sinus syndrome, second or third&#xD;
             degree AV block or previous documented syncope suspected to be due to bradycardia)&#xD;
             unless treated with a pacemaker&#xD;
&#xD;
         10. Known severe liver disease&#xD;
&#xD;
         11. Renal failure requiring dialysis&#xD;
&#xD;
         12. Known platelet count &lt;80x106/mL&#xD;
&#xD;
         13. Known hemoglobin &lt;9 g/dL&#xD;
&#xD;
         14. Pregnant or breastfeeding women. *Women of childbearing age must use reliable birth&#xD;
             control (i.e. oral contraceptives) while participating in the study.&#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>+1-904-244-3378</phone>
    <email>dominick.angiolillo@jax.ufl.edu</email>
  </overall_contact>
  <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>
    <investigator>
      <last_name>Francesco Franchi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>June 7, 2023</last_update_submitted>
  <last_update_submitted_qc>June 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>diabetes mellitus</keyword>
  <keyword>ticagrelor</keyword>
  <keyword>clopidogrel</keyword>
  <keyword>percutaneous coronary intervention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <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/NCT04484259
org study id: IRB202001694
nct id: NCT04484259
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Recent studies have shown that withdrawing aspirin and maintaining P2Y12 inhibitor
      monotherapy for up to 12 months post-PCI, after a brief period of DAPT, reduces bleeding
      without increasing ischemic harm. Such effects have shown to of particular benefit in
      patients with diabetes mellitus (DM). However, if an aspirin-free approach can be considered
      after this time frame is a matter of debate. The aim of this study is to assess the PD
      effects of ticagrelor 60 mg with and without aspirin therapy in CAD patients and to compare
      this with a standard DAPT regimen of aspirin plus clopidogrel.
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care
      for the prevention of thrombotic complications in patients with coronary artery disease (CAD)
      undergoing percutaneous coronary interventions (PCI). However, such ischemic benefit occurs
      at the expense of enhanced bleeding, the risk of which increases in a graded fashion with
      prolonged exposure to DAPT. Recent studies have shown that withdrawing aspirin and
      maintaining P2Y12 inhibitor monotherapy for up to 12 months post-PCI, after a brief period of
      DAPT, reduces bleeding without increasing ischemic harm. Such effects have shown to of
      particular benefit in patients with diabetes mellitus (DM). However, if an aspirin-free
      approach can be considered after this time frame is a matter of debate. In fact, current
      guidelines recommend maintaining P2Y12 inhibiting therapy for high risk patients but which
      all imply background use of aspirin. P2Y12 inhibitors for long-term (beyond 12 months)
      secondary prevention mainly include clopidogrel and ticagrelor. In particular, the dosing
      regimen for clopidogrel remains the standard 75 mg qd, whereas ticagrelor dosing is
      recommended to be reduced from 90 mg bid to 60 mg bid. However, of these regimens the
      pharmacodynamics (PD) effects of ticagrelor 60 mg in the absence of aspirin has not yet been
      tested. Because DM patients are likely to continue with long-term P2Y12 inhibitor therapy,
      defining the optimal antithrombotic approach for these patients is of critical importance. In
      light of the above made observations, patients with DM represent an ideal population to
      define the antiplatelet effects of a ticagrelor 60 mg monotherapy regimen. The aim of this
      study is to assess the PD effects of ticagrelor 60 mg with and without aspirin therapy in CAD
      patients and to compare this with a standard DAPT regimen of aspirin plus clopidogrel.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective randomized
primary purpose: Treatment
masking: None (Open Label)
masking description: Staff performing PK/PD assessments will remain blinded to treatment assignment.
measure: P2Y12 reaction units (PRU)
time frame: 10 days
description: The primary end-point of the study is the comparison of the PRU determined by VerifyNow PRU between between aspirin plus ticagrelor 60 mg and ticagrelor 60 mg monotherapy (trough effect pre-dosing)
arm group label: Ticagrelor
arm group type: Experimental
description: ticagrelor 60 mg bid monotherapy
arm group label: Aspirin plus Clopidogrel
arm group type: Active Comparator
description: aspirin 81 mg qd plus clopidogrel 75 mg qd
arm group label: Aspirin plus Ticagrelor
arm group type: Active Comparator
description: aspirin 81 mg qd plus ticagrelor 60 mg bid
intervention type: Drug
intervention name: Ticagrelor monotherapy
description: Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.
arm group label: Ticagrelor
other name: Brilinta
intervention type: Drug
intervention name: Ticagrelor plus aspirin
description: Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.
arm group label: Aspirin plus Ticagrelor
other name: Brilinta
intervention type: Drug
intervention name: Clopidogrel with aspirin
description: Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.
arm group label: Aspirin plus 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: +1-904-244-3378
email: dominick.angiolillo@jax.ufl.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Aspirin
mesh term: Clopidogrel
mesh term: Ticagrelor
sharing ipd: No