<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/NCT03247972</url>
  </required_header>
  <id_info>
    <org_study_id>16-2584</org_study_id>
    <nct_id>NCT03247972</nct_id>
  </id_info>
  <brief_title>Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease</brief_title>
  <official_title>Antiplatelet Effects of Evolocumab in Patients With Peripheral Arterial Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Inova Health Care Services</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Inova Health Care Services</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Monoclonal antibodies against PCSK9 are innovative agents that provide very potent LDL&#xD;
      reduction when administered on top of statins. PCSK9 antibodies prevent LDL receptor&#xD;
      degradation and enhance circulatory LDL cholesterol clearance. High LDL is a major risk&#xD;
      factor for PAD and therefore lipid-lowering therapy constitutes another important therapeutic&#xD;
      intervention for patients with PAD. Evolocumab is a common PCSK-9 inhibitor that has been&#xD;
      shown to reduce plasma LDL.&#xD;
&#xD;
      In this study sixty subjects will be treated with high dose statins for 8 weeks followed by 8&#xD;
      weeks of high dose statin + evolocumab (420mg/4 wk) therapy. The laboratory assessments will&#xD;
      be performed at the screening (baseline), after 8 weeks of high-dose statin therapy, and 24&#xD;
      hr and 8 weeks after high dose statin + evolocumab therapy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 11, 2017</start_date>
  <completion_date type="Anticipated">July 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Relative difference in ADP-induced platelet aggregation between high-dose statin therapy, and high-dose statin plus evolocumab therapy.</measure>
    <time_frame>16 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative differences in AA- and collagen-induced platelet aggregation between high dose statin therapy and evolocumab plus high-dose stain therapy.</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative differences in platelet bound p-selectin, oxLDL, soluble LOX-1 receptor, between high dose statin therapy and evolocumab plus high-dose stain therapy.</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative differences in lipid profile, oxLDL, soluble LOX-1 receptor, fibrinogen, hsCRP, p-selectin, atherox (soluble markers) between high dose statin therapy and evolocumab plus high-dose stain therapy.</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative differences in platelet-fibrin clot characteristics and shear-induced platelet aggregation between high dose statin therapy and evolocumab and high-dose stain therapy.</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Peripheral Arterial Disease</condition>
  <arm_group>
    <arm_group_label>Patients with PAD</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Evolocumab</intervention_name>
    <description>Sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.</description>
    <arm_group_label>Patients with PAD</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Sixty patients with symptomatic PAD, as evidenced by:&#xD;
&#xD;
          -  either intermittent claudication with ABI &lt;0.90, or&#xD;
&#xD;
          -  peripheral arterial revascularization procedure, or&#xD;
&#xD;
          -  amputation due to atherosclerotic disease.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Criteria: Inclusion Criteria:&#xD;
&#xD;
        Symptomatic PAD, as evidenced by either&#xD;
&#xD;
          -  intermittent claudication with ABI &lt;0.90, or&#xD;
&#xD;
          -  peripheral arterial revascularization procedure, or&#xD;
&#xD;
          -  amputation due to atherosclerotic disease.&#xD;
&#xD;
          -  Subject may be of either sex and of any race, and must be &gt;18 years of age.&#xD;
&#xD;
          -  Subject agrees to not participate in any other investigational or invasive clinical&#xD;
             study for a period of 4 months during the study period&#xD;
&#xD;
          -  Subject must be willing and able to give appropriate informed consent.&#xD;
&#xD;
          -  The subject is able to read and has signed and dated the informed consent document&#xD;
             including authorization permitting release of personal health information approved by&#xD;
             the investigator's Institutional Review Board (IRB).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior use of any PCSK9 inhibition treatment Participation in any investigational study&#xD;
             within the last 60 days.&#xD;
&#xD;
          -  Severe renal dysfunction, defined as an eGFR &lt;20 mL/min/1.73 m2 at screening&#xD;
&#xD;
          -  Active liver disease or hepatic dysfunction, defined as AST or ALT &gt;3 x ULN as&#xD;
             determined by central laboratory analysis at screening&#xD;
&#xD;
          -  Recipient of any major organ transplant (e.g., lung, liver, heart, bone marrow, renal)&#xD;
&#xD;
          -  Known major active infection or major hematologic, renal, metabolic, gastrointestinal,&#xD;
             or endocrine dysfunction in the judgment of the investigator&#xD;
&#xD;
          -  Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast&#xD;
             ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 10 years&#xD;
&#xD;
          -  Subject has received drugs via a systemic route that have known major interactions&#xD;
             with background statin therapy within 1 month before randomization or is likely to&#xD;
             require such treatment during the study period (e.g. cyclosporine, clarithromycin, HIV&#xD;
             protease inhibitors, gemfibrozil)&#xD;
&#xD;
          -  Female subject who is unwilling to use at least 2 effective birth control methods for&#xD;
             at least 1 month before screening and 15 weeks after the end of treatment with&#xD;
             investigational products, unless the subject is sterilized or postmenopausal.&#xD;
&#xD;
          -  Subject is pregnant or breast feeding, or planning to become pregnant or to breastfeed&#xD;
             during receipt of investigational products and within 15 weeks after the end of study&#xD;
             treatment&#xD;
&#xD;
          -  Known previous hypersensitivity reaction/s to the investigational products' active&#xD;
             components and excipients.&#xD;
&#xD;
          -  Subjects treated with any antithrombotic agents except aspirin.&#xD;
&#xD;
          -  Subject likely to not be available to complete all protocol-required study visits or&#xD;
             procedures, to the best of the subject's and investigator's knowledge&#xD;
&#xD;
          -  History or evidence of any other clinically significant disorder, condition, or&#xD;
             disease other than those outlined above that, in the opinion of the investigator, may&#xD;
             compromise the ability of the subject to give written informed consent, would pose a&#xD;
             risk to subject safety or interfere with the study evaluation, procedures, or&#xD;
             completion.&#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_contact>
    <last_name>Kevin Bliden, BS/MBA</last_name>
    <phone>703-776-7702</phone>
    <email>kevin.bliden@inova.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Inova Fairfax Hospital</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kevin Bliden, MS/MBA</last_name>
      <phone>703-776-7702</phone>
      <email>kevin.bliden@inova.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>June 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>August 21, 2018</last_update_submitted>
  <last_update_submitted_qc>August 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2018</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>Peripheral Arterial Disease</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Evolocumab</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 27, 2022</submitted>
    <returned>June 6, 2023</returned>
    <submitted>June 26, 2023</submitted>
  </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/NCT03247972
org study id: 16-2584
nct id: NCT03247972
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Monoclonal antibodies against PCSK9 are innovative agents that provide very potent LDL
      reduction when administered on top of statins. PCSK9 antibodies prevent LDL receptor
      degradation and enhance circulatory LDL cholesterol clearance. High LDL is a major risk
      factor for PAD and therefore lipid-lowering therapy constitutes another important therapeutic
      intervention for patients with PAD. Evolocumab is a common PCSK-9 inhibitor that has been
      shown to reduce plasma LDL.

      In this study sixty subjects will be treated with high dose statins for 8 weeks followed by 8
      weeks of high dose statin + evolocumab (420mg/4 wk) therapy. The laboratory assessments will
      be performed at the screening (baseline), after 8 weeks of high-dose statin therapy, and 24
      hr and 8 weeks after high dose statin + evolocumab therapy
observational model: Case-Only
time perspective: Prospective
measure: Relative difference in ADP-induced platelet aggregation between high-dose statin therapy, and high-dose statin plus evolocumab therapy.
time frame: 16 weeks
measure: Relative differences in AA- and collagen-induced platelet aggregation between high dose statin therapy and evolocumab plus high-dose stain therapy.
time frame: 16 weeks
measure: Relative differences in platelet bound p-selectin, oxLDL, soluble LOX-1 receptor, between high dose statin therapy and evolocumab plus high-dose stain therapy.
time frame: 16 weeks
measure: Relative differences in lipid profile, oxLDL, soluble LOX-1 receptor, fibrinogen, hsCRP, p-selectin, atherox (soluble markers) between high dose statin therapy and evolocumab plus high-dose stain therapy.
time frame: 16 weeks
measure: Relative differences in platelet-fibrin clot characteristics and shear-induced platelet aggregation between high dose statin therapy and evolocumab and high-dose stain therapy.
time frame: 16 weeks
arm group label: Patients with PAD
intervention type: Drug
intervention name: Evolocumab
description: Sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
arm group label: Patients with PAD
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin Bliden, BS/MBA
phone: 703-776-7702
email: kevin.bliden@inova.org
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
mesh term: Evolocumab
submitted: July 27, 2022
returned: June 6, 2023
submitted: June 26, 2023