<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/NCT02970604</url>
  </required_header>
  <id_info>
    <org_study_id>RCSIMCT20152017</org_study_id>
    <nct_id>NCT02970604</nct_id>
  </id_info>
  <brief_title>PPARGC1β and CNTN4 Genotype Aspirin Study</brief_title>
  <official_title>PPARGC1β And CNTN4 Genotype as a Pharmacogenetic Assay of Thrombosis and Bleeding Risks - a Cross-Over Controlled Trial of Aspirin in Individuals at Increased Cardiovascular Risk.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal College of Surgeons, Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal College of Surgeons, Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Heart attacks and strokes are common causes of death worldwide. These events occur in part,&#xD;
      due to increased activity of platelets, which cause clotting (thrombosis) within heart and&#xD;
      brain blood vessels.&#xD;
&#xD;
      Anti-platelet therapies (e.g. aspirin) reduce the likelihood of platelet thrombosis and&#xD;
      therefore protect against heart attacks and strokes. However serious bleeding into the gut&#xD;
      and brain occurs in a number of individuals prescribed aspirin. Currently, there is no&#xD;
      reliable method for assessing the relative risks of thrombosis versus bleeding in individual&#xD;
      patients prior to or during aspirin therapy.&#xD;
&#xD;
      We have recently discovered that individuals with a particular genetic make-up, those with&#xD;
      genetic variants in two genes called PPARGC1β and CNTN4, demonstrate more active (sticky)&#xD;
      platelets. We then found that these same individuals suffered a greater number of&#xD;
      cardiovascular events. Interestingly, low dose aspirin suppressed the excessive platelet&#xD;
      stickiness and protected against heart attacks and strokes in these patients.&#xD;
&#xD;
      In this project, we aim to confirm and extend the above findings. We hope that testing for&#xD;
      PPARGC1β and CNTN4 genetic variants will allow us to identify which patients will benefit&#xD;
      from low dose aspirin therapy - i.e. receive protection from heart attacks and strokes, but&#xD;
      not suffer any bleeding complications.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2016</start_date>
  <completion_date type="Anticipated">February 2018</completion_date>
  <primary_completion_date type="Anticipated">February 2018</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Urinary Thromboxane B2/Creatinine Ratio</measure>
    <time_frame>Baseline</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-enteric coated Aspirin 75mg once daily for 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No treatment for 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>Non enteric coated aspirin</description>
    <arm_group_label>Aspirin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must be male or female outpatients.&#xD;
&#xD;
          -  Age must be greater than 18 years.&#xD;
&#xD;
          -  Subjects must be able and willing to give written informed consent, and to comply with&#xD;
             the requirements of this study protocol.&#xD;
&#xD;
          -  Subjects must be at intermediate to high cardiovascular risk as determined by a&#xD;
             calculated 5 year CVD risk of 5% or greater (calculated using the 1991 Anderson&#xD;
             Framingham risk equation with adjustments as defined by the New Zealand Guidelines&#xD;
             Group recommendations)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18 years.&#xD;
&#xD;
          -  Previous MI, stroke, transient ischaemic attack (TIA) or known CAD.&#xD;
&#xD;
          -  Subjects who have any other significant disease or disorder (including concurrent&#xD;
             malignancy) which, in the opinion of the investigator, may either put the subject at&#xD;
             risk by participation in the study, or may influence the result of the study.&#xD;
&#xD;
          -  Known history of, or documented positive hepatitis B or C or HIV infection&#xD;
&#xD;
          -  AST or ALT ≥ 3 x ULN.&#xD;
&#xD;
          -  Creatinine clearance (CrCl) &lt; 60 mL/min measured by 24-hour urine collection or&#xD;
             estimated by the Cockcroft and Gault formula.&#xD;
&#xD;
          -  Female subjects who are pregnant or breast-feeding or considering becoming pregnant&#xD;
             during the study, or with childbearing potential without using a medically accepted&#xD;
             method of contraception (see notes 1-5 below)&#xD;
&#xD;
          -  Patients already taking aspirin.&#xD;
&#xD;
          -  Patients already taking anti-platelet agents (clopidogrel, ticagrelor etc),&#xD;
             non-steroidal anti inflammatory drugs (NSAIDs), or anticoagulants (heparin, warfarin,&#xD;
             dabigatran, etc).&#xD;
&#xD;
          -  Patients who have a known intolerance to aspirin.&#xD;
&#xD;
          -  Patients who have a contra-indication to aspirin as detailed below:&#xD;
&#xD;
               -  Hypersensitivity to salicylic acid compounds or prostaglandin synthetase&#xD;
                  inhibitors (e.g. certain asthma patients who may suffer an attack or faint and&#xD;
                  certain patients who may suffer from bronchospasm, rhinitis and urticaria) and to&#xD;
                  any of the excipients.&#xD;
&#xD;
               -  Active, or history of recurrent peptic ulcer and/or gastric/intestinal&#xD;
                  haemorrhage, or other kinds of bleeding such as cerebrovascular haemorrhages.&#xD;
&#xD;
               -  Haemorrhagic diathesis; coagulation disorders such as haemophilia and&#xD;
                  thrombocytopenia.&#xD;
&#xD;
               -  Patients who are suffering from gout.&#xD;
&#xD;
               -  Severe hepatic impairment.&#xD;
&#xD;
               -  Severe renal impairment.&#xD;
&#xD;
               -  Patients taking methotrexate used at doses &gt;15mg/week.&#xD;
&#xD;
          -  History of peptic ulcer disease or upper gastrointestinal bleeding.&#xD;
&#xD;
          -  Subjects who have a history of drug or alcohol use that, in the opinion of the&#xD;
             investigator, would interfere with adherence to study requirements.&#xD;
&#xD;
          -  Participants unlikely to comply well with study treatments or with the scheduled&#xD;
             visits.&#xD;
&#xD;
          -  Scheduled for procedures requiring general anaesthesia during 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>Alice Stanton, MB PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal College of Surgeons in Ireland</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kirstyn James, MB</last_name>
    <phone>0035318093706</phone>
    <phone_ext>3706</phone_ext>
    <email>kirsjames@rcsi.ie</email>
  </overall_contact>
  <location>
    <facility>
      <name>Royal College of Surgeons in Ireland</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kirstyn James, MB</last_name>
      <phone>0035318093706</phone>
      <phone_ext>3706</phone_ext>
      <email>kirsjames@rcsi.ie</email>
    </contact>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>November 18, 2016</last_update_submitted>
  <last_update_submitted_qc>November 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Aspirin</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/NCT02970604
org study id: RCSIMCT20152017
nct id: NCT02970604
lead sponsor: 
has dmc: No
Heart attacks and strokes are common causes of death worldwide. These events occur in part,
      due to increased activity of platelets, which cause clotting (thrombosis) within heart and
      brain blood vessels.

      Anti-platelet therapies (e.g. aspirin) reduce the likelihood of platelet thrombosis and
      therefore protect against heart attacks and strokes. However serious bleeding into the gut
      and brain occurs in a number of individuals prescribed aspirin. Currently, there is no
      reliable method for assessing the relative risks of thrombosis versus bleeding in individual
      patients prior to or during aspirin therapy.

      We have recently discovered that individuals with a particular genetic make-up, those with
      genetic variants in two genes called PPARGC1β and CNTN4, demonstrate more active (sticky)
      platelets. We then found that these same individuals suffered a greater number of
      cardiovascular events. Interestingly, low dose aspirin suppressed the excessive platelet
      stickiness and protected against heart attacks and strokes in these patients.

      In this project, we aim to confirm and extend the above findings. We hope that testing for
      PPARGC1β and CNTN4 genetic variants will allow us to identify which patients will benefit
      from low dose aspirin therapy - i.e. receive protection from heart attacks and strokes, but
      not suffer any bleeding complications.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Urinary Thromboxane B2/Creatinine Ratio
time frame: Baseline
arm group label: Aspirin
arm group type: Experimental
description: Non-enteric coated Aspirin 75mg once daily for 7 days
arm group label: No treatment
arm group type: No Intervention
description: No treatment for 7 days
intervention type: Drug
intervention name: Aspirin
description: Non enteric coated aspirin
arm group label: Aspirin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alice Stanton, MB PhD
role: Principal Investigator
affiliation: Royal College of Surgeons in Ireland
last name: Kirstyn James, MB
phone: 0035318093706
phone ext: 3706
email: kirsjames@rcsi.ie
facility: 
status: Recruiting
contact: 
country: Ireland
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Aspirin
sharing ipd: No