<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/NCT01732523</url>
  </required_header>
  <id_info>
    <org_study_id>EK145/12</org_study_id>
    <secondary_id>PZ00P3_142419/1</secondary_id>
    <nct_id>NCT01732523</nct_id>
  </id_info>
  <brief_title>Predictive Value of Neovascularization Within Asymptomatic Carotis Stenosis on CEUS</brief_title>
  <official_title>Predictive Value of Carotid Lesion Neovascularization Detected by Contrast-enhanced Ultrasound (CEUS) in Patients With Asymptomatic Carotid Stenosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swiss National Science Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Atherosclerosis is a chronic, systemic and progressive disease affecting different arterial&#xD;
      blood vessels in the body. Atherosclerotic lesions silently progress from small plaques to&#xD;
      severe stenosis and may remain asymptomatic for years. Unstable plaques and stenosis (also&#xD;
      called vulnerable plaques), however, are prone to rupture leading to myocardial infarction,&#xD;
      or stroke. The proliferation of the small arteries that are distributed to the outer and&#xD;
      middle coats of the larger blood vessels (vasa vasorum) and within the atherosclerotic&#xD;
      plaques (neovascularization) are inherently linked with the atherosclerotic plaque&#xD;
      development, plaque inflammation and vulnerability. By injecting ultrasound contrast agents&#xD;
      (microbubbles) into the blood stream, it is possible to detect this microcirculation of the&#xD;
      vessel wall and the neovascularization within the atherosclerotic plaque using a&#xD;
      contrast-enhanced ultrasound (CEUS) imaging technique. Particularly, CEUS of the carotid&#xD;
      artery has been introduced as a non-invasive technique to improve detection of carotid&#xD;
      atherosclerosis and to evaluate the presence of carotid plaque neovascularization which has&#xD;
      emerged as a new marker for plaque vulnerability. The project investigates the predictive&#xD;
      value of the detection of carotid plaque neovascularization on CEUS imaging in patients with&#xD;
      asymptomatic carotid artery stenosis regarding the progression of the carotid atherosclerotic&#xD;
      lesion and future vascular events including myocardial infarction, stroke or vascular&#xD;
      intervention. The investigators hypothesize that neovascularization within the carotid lesion&#xD;
      will significantly be more pronounced in patients with progressive carotid lesions and in&#xD;
      patients suffering future vascular events during. The project will support the concept that&#xD;
      intraplaque neovascularization is associated with plaque instability and vulnerability and&#xD;
      therefore, the use of CEUS may provide an additional non-invasive, simple, safe, and reliable&#xD;
      imaging modality to risk stratify individuals. The identification of vulnerable that are at&#xD;
      increased risk of rupture by identification of intraplaque neovascularization is expected to&#xD;
      improve the prediction of future vascular events and thus allow for better treatment&#xD;
      selection. It will help the clinician to further risk stratify carotid stenosis.&#xD;
      Particularly, it will help to identify unstable carotid stenosis that may already benefit&#xD;
      from invasive therapy as carotid thromboendarterectomy and stenting.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Vascular event or vascular intervention</measure>
    <time_frame>5 years</time_frame>
    <description>The endpoint assessed will be the occurrence of any vascular event or vascular intervention. This composite end point includes any death of presumed vascular origin (fatal stroke, fatal myocardial infarction, sudden death, other vascular death), nonfatal stroke and TIA, nonfatal myocardial infarction, and any arterial vascular intervention that had not already been planned at the time of inclusion (eg, carotid surgery or angioplasty/stenting, coronary bypass, percutaneous coronary intervention, peripheral vascular surgery or angioplasty/stenting). All events and vascular interventions should be confirmed by hospital discharge report and medical files.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression of carotid stenosis over time</measure>
    <time_frame>5 years</time_frame>
    <description>progression of carotid stenosis over time (progression in the lesion area, lesion volume, and degree of stenosis) assessed by yearly repeated standard carotid ultrasound study. Based on the yearly repeated standard carotid ultrasound studies progression rate of the lesion area and the lesion volume can be quantified for each stenosis and specify as continuous variable in cm2/year (area progression/year) and in cm3/year (volume progression/year). Additionally, the progression of the grade of stenosis will be quantified as categorical variable by determining the change of the stenosis category over time (30-49%, 50-69%, 70-99%, 100%) (Stable stenosis or increase in 1, 2, or 3 categories over 5 years).</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Carotid Stenosis</condition>
  <arm_group>
    <arm_group_label>No treatment</arm_group_label>
    <description>No intervention</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        In-and out-patients referred to our ultrasound laboratory for carotid ultrasound for a&#xD;
        clinical indication (preoperative, carotid murmur, known carotid lesion) will be ask to&#xD;
        participate in this clinical study and will be asked to undergo study carotid ultrasound&#xD;
        including CEUS.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients age &gt; 18 years&#xD;
&#xD;
          -  Asymptomatic (no history of cerebrovascular event in the corresponding vessel&#xD;
             territory) ≥30% carotid stenosis on standard carotid ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of previous carotid endarterectomy or carotid stenting.&#xD;
&#xD;
          -  Heart failure (HYHA III or IV)&#xD;
&#xD;
          -  Myocardial infarction (&lt;7d)&#xD;
&#xD;
          -  Severe pulmonal-arterial hypertension (pulmonal arterial pressure &gt;90mmHg) based on&#xD;
             clinical information (history of pulmonal arterial pressure, dyspnea on exertion New&#xD;
             York Heart Association (NYHA) III and NYHA IV)&#xD;
&#xD;
          -  pregnancy (pregnancy test in patients of childbearing age: &lt;50 years and/or less than&#xD;
             2 years after menopause)&#xD;
&#xD;
          -  Follow-up is not considered feasible&#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>Daniel Staub, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Basle, Angiology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Daniel Staub, MD</last_name>
    <phone>+41612655154</phone>
    <email>daniel.staub@usb.ch</email>
  </overall_contact>
  <location>
    <facility>
      <name>Unversity Hospital Basel, Angiology</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel Staub, MD</last_name>
      <phone>+41612655154</phone>
      <email>daniel.staub@usb.ch</email>
    </contact>
    <investigator>
      <last_name>Daniel Staub, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 16, 2012</study_first_submitted>
  <study_first_submitted_qc>November 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <last_update_submitted>April 29, 2021</last_update_submitted>
  <last_update_submitted_qc>April 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Carotid stenosis</keyword>
  <keyword>Vasa Vasorum</keyword>
  <keyword>Ultrasonography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carotid Stenosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
    <mesh_term>Neovascularization, Pathologic</mesh_term>
  </condition_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/NCT01732523
org study id: EK145/12
secondary id: PZ00P3_142419/1
nct id: NCT01732523
lead sponsor: 
collaborator: 
has dmc: No
Atherosclerosis is a chronic, systemic and progressive disease affecting different arterial
      blood vessels in the body. Atherosclerotic lesions silently progress from small plaques to
      severe stenosis and may remain asymptomatic for years. Unstable plaques and stenosis (also
      called vulnerable plaques), however, are prone to rupture leading to myocardial infarction,
      or stroke. The proliferation of the small arteries that are distributed to the outer and
      middle coats of the larger blood vessels (vasa vasorum) and within the atherosclerotic
      plaques (neovascularization) are inherently linked with the atherosclerotic plaque
      development, plaque inflammation and vulnerability. By injecting ultrasound contrast agents
      (microbubbles) into the blood stream, it is possible to detect this microcirculation of the
      vessel wall and the neovascularization within the atherosclerotic plaque using a
      contrast-enhanced ultrasound (CEUS) imaging technique. Particularly, CEUS of the carotid
      artery has been introduced as a non-invasive technique to improve detection of carotid
      atherosclerosis and to evaluate the presence of carotid plaque neovascularization which has
      emerged as a new marker for plaque vulnerability. The project investigates the predictive
      value of the detection of carotid plaque neovascularization on CEUS imaging in patients with
      asymptomatic carotid artery stenosis regarding the progression of the carotid atherosclerotic
      lesion and future vascular events including myocardial infarction, stroke or vascular
      intervention. The investigators hypothesize that neovascularization within the carotid lesion
      will significantly be more pronounced in patients with progressive carotid lesions and in
      patients suffering future vascular events during. The project will support the concept that
      intraplaque neovascularization is associated with plaque instability and vulnerability and
      therefore, the use of CEUS may provide an additional non-invasive, simple, safe, and reliable
      imaging modality to risk stratify individuals. The identification of vulnerable that are at
      increased risk of rupture by identification of intraplaque neovascularization is expected to
      improve the prediction of future vascular events and thus allow for better treatment
      selection. It will help the clinician to further risk stratify carotid stenosis.
      Particularly, it will help to identify unstable carotid stenosis that may already benefit
      from invasive therapy as carotid thromboendarterectomy and stenting.
observational model: Cohort
time perspective: Prospective
measure: Vascular event or vascular intervention
time frame: 5 years
description: The endpoint assessed will be the occurrence of any vascular event or vascular intervention. This composite end point includes any death of presumed vascular origin (fatal stroke, fatal myocardial infarction, sudden death, other vascular death), nonfatal stroke and TIA, nonfatal myocardial infarction, and any arterial vascular intervention that had not already been planned at the time of inclusion (eg, carotid surgery or angioplasty/stenting, coronary bypass, percutaneous coronary intervention, peripheral vascular surgery or angioplasty/stenting). All events and vascular interventions should be confirmed by hospital discharge report and medical files.
measure: Progression of carotid stenosis over time
time frame: 5 years
description: progression of carotid stenosis over time (progression in the lesion area, lesion volume, and degree of stenosis) assessed by yearly repeated standard carotid ultrasound study. Based on the yearly repeated standard carotid ultrasound studies progression rate of the lesion area and the lesion volume can be quantified for each stenosis and specify as continuous variable in cm2/year (area progression/year) and in cm3/year (volume progression/year). Additionally, the progression of the grade of stenosis will be quantified as categorical variable by determining the change of the stenosis category over time (30-49%, 50-69%, 70-99%, 100%) (Stable stenosis or increase in 1, 2, or 3 categories over 5 years).
arm group label: No treatment
description: No intervention
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Staub, MD
role: Principal Investigator
affiliation: University Hospital Basle, Angiology
last name: Daniel Staub, MD
phone: +41612655154
email: daniel.staub@usb.ch
facility: 
status: Recruiting
contact: 
investigator: 
country: Switzerland
responsible party type: Sponsor
mesh term: Carotid Stenosis
mesh term: Constriction, Pathologic
mesh term: Neovascularization, Pathologic