<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/NCT02261922</url>
  </required_header>
  <id_info>
    <org_study_id>FM240</org_study_id>
    <nct_id>NCT02261922</nct_id>
  </id_info>
  <brief_title>Ticagrelor and Endothelial Function</brief_title>
  <official_title>A Prospective Randomized Double Blind Study to Evaluate the Effect of Ticagrelor on Endothelial Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hotel Dieu de France Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hotel Dieu de France Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the effect of ticagrelor on endothelial function as measured by flow mediated&#xD;
      dilation of the brachial artery. This will be compared to prasugrel.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      Demonstrate an improvement in endothelial function with ticagrelor&#xD;
&#xD;
      Introduction and hypothesis:&#xD;
&#xD;
      Ticagrelor and prasugrel are 2 new platelet antagonists. Both are superior to clopidogrel&#xD;
      when used in acute coronary syndromes. However, only ticagrelor reduced cardiovascular&#xD;
      mortality by almost 20%. Prasugrel reduced the composite clinical end point of cardiovascular&#xD;
      mortality, myocardial infarction and stroke, but did not decrease mortality. The exact&#xD;
      mechanism of mortality reduction with ticagrelor is unclear.&#xD;
&#xD;
      Some side effects of ticagrelor, such as brady-arrhythmias and dyspnea may be related to&#xD;
      adenosine release. It is thus possible, that this drug may liberate significant amount of&#xD;
      adenosine. Prior studies have demonstrated that adenosine has beneficial effects on the&#xD;
      endothelial function and that it improves the outcome of patient with acute coronary&#xD;
      syndromes.&#xD;
&#xD;
      It is thus possible that ticagrelor may improve endothelial function through an adenosine&#xD;
      like effect. This effect is independent from platelet inhibition.&#xD;
&#xD;
      Prasugrel has the same platelet inhibition effect compared to ticagrelor, but our hypothesis&#xD;
      is that it does not have an adenosine like effect and thus does not improve endothelial&#xD;
      function.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      This is a prospective, randomized, double blind, cross-over study comparing 2 new platelet&#xD;
      inhibitors that have the same potency: ticagrelor and prasugrel.&#xD;
&#xD;
      Patients with stable coronary artery disease will be randomized to one of these 2 drugs.&#xD;
      Patients will receive one of the 2 drugs for a period of 8 +/- 2 days, they will then stop&#xD;
      the drug for a period of 14 +/- 2 days, and they will then cross over and receive the other&#xD;
      drug for a period of 8 +/- 2 days.&#xD;
&#xD;
      All patients will have the following measurements:&#xD;
&#xD;
        -  Flow mediated Dilation (FMD) of the brachial artery&#xD;
&#xD;
        -  Platelet aggregation in response to ADP&#xD;
&#xD;
      All measurements will be done at:&#xD;
&#xD;
        -  Baseline 1 (prior to starting drug 1)&#xD;
&#xD;
        -  At 8 +/- 2 days (peak effect of drug 1)&#xD;
&#xD;
        -  Baseline 2 (at 14+/- 2 days; after washout and prior to starting drug 2)&#xD;
&#xD;
        -  At 8 +/- 2 days after baseline 2 (peak effect of drug 2)&#xD;
&#xD;
      Measure of FMD of the brachial artery:&#xD;
&#xD;
      It will be performed according to the Academic Medical Center of Amsterdam pre-established&#xD;
      protocol.&#xD;
&#xD;
      Measure of platelet aggregation:&#xD;
&#xD;
      It will be performed with the multiplate aggregometer&#xD;
&#xD;
      Study End-Points:&#xD;
&#xD;
        -  Primary: change in FMD before and after each of the 2 drugs&#xD;
&#xD;
        -  Secondary: Change in platelet aggregation before and after each of the 2 drugs&#xD;
&#xD;
        -  Possible another secondary end-point: Change in NO activity in the blood before and&#xD;
           after each of the 2 drugs&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">November 2015</completion_date>
  <primary_completion_date type="Anticipated">October 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>flow mediated dilation of the brachial artery</measure>
    <time_frame>8 +/- 2 days</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Antiplatelet Agents; Endothelial Function; Pleotropic Effects</condition>
  <arm_group>
    <arm_group_label>ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ticagrelor treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>prasugrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>prasugrel treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ticagrelor</intervention_name>
    <arm_group_label>ticagrelor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prasugrel</intervention_name>
    <arm_group_label>prasugrel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  - Prior MI &gt; 1 year old&#xD;
&#xD;
          -  Prior PCI &gt; 1 year old&#xD;
&#xD;
          -  Prior CABG &gt; 3 months old&#xD;
&#xD;
          -  Known lesion causing more than 50% stenosis on coronary angiography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute coronary syndrome within the last 6 months&#xD;
&#xD;
          -  Any history of bleeding&#xD;
&#xD;
          -  Age &gt; 75 years&#xD;
&#xD;
          -  Weight &lt; 65 kg&#xD;
&#xD;
          -  Prior stroke or TIA&#xD;
&#xD;
          -  Platelet count &lt; 100,000&#xD;
&#xD;
          -  Hemoglobin &lt; 11 mg/dL&#xD;
&#xD;
          -  Patients who have received ticagrelor, prasugrel or clopidogrel in the 3 months that&#xD;
             preceded randomization&#xD;
&#xD;
          -  Patients who are taking anti-thrombotic therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Rabih Azar, MD, MPH</last_name>
    <email>razar@usj.edu.lb</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hotel Dieu de France Hospital</name>
      <address>
        <city>Achrafieh</city>
        <state>Beirut</state>
        <zip>Beirut</zip>
        <country>Lebanon</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rabih R Azar, MD, MPH</last_name>
      <phone>+9611615300</phone>
      <phone_ext>9408</phone_ext>
      <email>razar@usj.edu.lb</email>
    </contact>
  </location>
  <location_countries>
    <country>Lebanon</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>October 9, 2014</last_update_submitted>
  <last_update_submitted_qc>October 9, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 10, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hotel Dieu de France Hospital</investigator_affiliation>
    <investigator_full_name>Rabih Azar</investigator_full_name>
    <investigator_title>Chief of Cardiology, Hotel Dieu de France Hospital</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ticagrelor</mesh_term>
    <mesh_term>Prasugrel Hydrochloride</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02261922
org study id: FM240
nct id: NCT02261922
lead sponsor: 
has dmc: No
To evaluate the effect of ticagrelor on endothelial function as measured by flow mediated
      dilation of the brachial artery. This will be compared to prasugrel.
Objective:

      Demonstrate an improvement in endothelial function with ticagrelor

      Introduction and hypothesis:

      Ticagrelor and prasugrel are 2 new platelet antagonists. Both are superior to clopidogrel
      when used in acute coronary syndromes. However, only ticagrelor reduced cardiovascular
      mortality by almost 20%. Prasugrel reduced the composite clinical end point of cardiovascular
      mortality, myocardial infarction and stroke, but did not decrease mortality. The exact
      mechanism of mortality reduction with ticagrelor is unclear.

      Some side effects of ticagrelor, such as brady-arrhythmias and dyspnea may be related to
      adenosine release. It is thus possible, that this drug may liberate significant amount of
      adenosine. Prior studies have demonstrated that adenosine has beneficial effects on the
      endothelial function and that it improves the outcome of patient with acute coronary
      syndromes.

      It is thus possible that ticagrelor may improve endothelial function through an adenosine
      like effect. This effect is independent from platelet inhibition.

      Prasugrel has the same platelet inhibition effect compared to ticagrelor, but our hypothesis
      is that it does not have an adenosine like effect and thus does not improve endothelial
      function.

      Study design:

      This is a prospective, randomized, double blind, cross-over study comparing 2 new platelet
      inhibitors that have the same potency: ticagrelor and prasugrel.

      Patients with stable coronary artery disease will be randomized to one of these 2 drugs.
      Patients will receive one of the 2 drugs for a period of 8 +/- 2 days, they will then stop
      the drug for a period of 14 +/- 2 days, and they will then cross over and receive the other
      drug for a period of 8 +/- 2 days.

      All patients will have the following measurements:

        -  Flow mediated Dilation (FMD) of the brachial artery

        -  Platelet aggregation in response to ADP

      All measurements will be done at:

        -  Baseline 1 (prior to starting drug 1)

        -  At 8 +/- 2 days (peak effect of drug 1)

        -  Baseline 2 (at 14+/- 2 days; after washout and prior to starting drug 2)

        -  At 8 +/- 2 days after baseline 2 (peak effect of drug 2)

      Measure of FMD of the brachial artery:

      It will be performed according to the Academic Medical Center of Amsterdam pre-established
      protocol.

      Measure of platelet aggregation:

      It will be performed with the multiplate aggregometer

      Study End-Points:

        -  Primary: change in FMD before and after each of the 2 drugs

        -  Secondary: Change in platelet aggregation before and after each of the 2 drugs

        -  Possible another secondary end-point: Change in NO activity in the blood before and
           after each of the 2 drugs
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: flow mediated dilation of the brachial artery
time frame: 8 +/- 2 days
arm group label: ticagrelor
arm group type: Experimental
description: ticagrelor treatment
arm group label: prasugrel
arm group type: Active Comparator
description: prasugrel treatment
intervention type: Drug
intervention name: ticagrelor
arm group label: ticagrelor
intervention type: Drug
intervention name: prasugrel
arm group label: prasugrel
criteria: 
gender: All
minimum age: 21 Years
maximum age: 75 Years
healthy volunteers: No
last name: Rabih Azar, MD, MPH
email: razar@usj.edu.lb
facility: 
status: Recruiting
contact: 
country: Lebanon
responsible party type: Principal Investigator
investigator affiliation: Hotel Dieu de France Hospital
investigator full name: Rabih Azar
investigator title: Chief of Cardiology, Hotel Dieu de France Hospital
mesh term: Ticagrelor
mesh term: Prasugrel Hydrochloride