<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/NCT04470687</url>
  </required_header>
  <id_info>
    <org_study_id>APHP180482</org_study_id>
    <secondary_id>2019-A03331-56</secondary_id>
    <nct_id>NCT04470687</nct_id>
  </id_info>
  <brief_title>Ultrafast Ultrasound Imaging Assesment of Carotid Plaque Neovascularization</brief_title>
  <acronym>ULTRA-VASC</acronym>
  <official_title>Innovative Applications of Ultrafast Ultrasound Imaging in Peripheral Vascular Pathology: Evaluation of Carotid Plaque Vulnerability by Quantification of Neovascularization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Stroke is the second leading cause of death in the Western world and the leading cause of&#xD;
      major lifelong disability. About 15% of strokes are secondary to thrombosis or embolization&#xD;
      of an unstable atheromatous carotid plaque. In these symptomatic patients, the degree of&#xD;
      carotid stenosis is correlated with the risk of early recurrence. Patients with stenosis over&#xD;
      70% are therefore offered an endarterectomy, an operation to remove carotid plaque, to&#xD;
      prevent future strokes[1]. In asymptomatic patients, the degree of stenosis is a limited&#xD;
      predictor, and better risk stratification is required to assess the degree of plaque&#xD;
      vulnerability and stroke risk of the patient. The therapeutic decision towards endarterectomy&#xD;
      in addition to drug therapy is debated because of a variable and dependent benefit/risk&#xD;
      balance for each patient. A number of imaging parameters have been studied: ulceration,&#xD;
      heterogeneity, vascularization of the plaque for example, but their place is not well defined&#xD;
      [2].&#xD;
&#xD;
      The usual evaluation of carotid stenosis is by conventional Doppler ultrasound with&#xD;
      calculation of the degree of stenosis according to the NASCET criteria.&#xD;
&#xD;
      For symptomatic stenoses the intervention is recommended when above 70% and is discussed from&#xD;
      50% to 70% of NASCET stenosis degree.&#xD;
&#xD;
      For asymptomatic stenoses, the procedure is discussed when above 60% taking into account the&#xD;
      patient's life expectancy, the risk of the surgery and the unstable nature of the plaque [2].&#xD;
&#xD;
      Destabilization of the carotid plaque is partially induced by inflammation associated with&#xD;
      neo-vascularization. The detection of these new vessels by conventional contrast ultrasound&#xD;
      has already shown a distinction between stable and unstable plaques, by the presence or&#xD;
      absence of microbubbles in the plaque. However, this assessment is not very precise and only&#xD;
      the most vascularized plaques can be detected. Ultrafast ultrasound Imaging is a new&#xD;
      ultrasonic Imaging modality that allows detecting low speed flows, a tiny vascular structure&#xD;
      within the vessel wall.&#xD;
&#xD;
      RESEARCH HYPOTHESIS Plaques neo-vascularization would be more precisely detected and&#xD;
      characterized by ultrafast imaging coupled with microbubble injection than conventional&#xD;
      ultrasound imaging.&#xD;
&#xD;
      A better assessment of plaque instability could improve the selection of patients for carotid&#xD;
      endarterectomy and increase the benefit/risk ratio of this preventive surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      see above&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 17, 2021</start_date>
  <completion_date type="Anticipated">March 17, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 17, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neovascularization of the carotid plaque</measure>
    <time_frame>end of inclusions</time_frame>
    <description>Correlation BETWEEN the average signal strength of the carotid plaque analyzed after injection of ultrasound contrast medium by three-dimensional probe with UF-Doppler AND the number of neovessels determined by histological analysis of the carotid plaque (number of neovessels per section) studied.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plaque stable or unstable</measure>
    <time_frame>end of inclusions</time_frame>
    <description>analyzed after injection of ultrasound contrast medium by three-dimensional probe with UF-Doppler AND the plaque stability according to Oxford criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plaque symptomatic or not</measure>
    <time_frame>end of inclusions</time_frame>
    <description>Comparison BETWEEN the average signal strength of the carotid plaque analyzed after injection of ultrasound contrast medium by three-dimensional probe with UF-Doppler AND the symptomatic or asymptomatic status for stroke of the patient</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Carotid Stenosis</condition>
  <condition>Carotid Artery Diseases</condition>
  <condition>Carotid Atherosclerosis</condition>
  <condition>Carotid Artery Plaque</condition>
  <condition>Atheroma; Carotid Artery</condition>
  <arm_group>
    <arm_group_label>Carotid plaque or stenosis ultrasound enhanced UF assesment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>symptomatic or asymptomatic patients with atheromatous carotid stenosis scheduled for carotid endarterectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>contrast enhanced ultrafast ultrasound imaging</intervention_name>
    <description>Ultrasound contrast medium: SonoVue 8µL/mL (Bracco International BV) Ultrasound scanner: Aixplorer® device marketed by SuperSonic Imagine©, CE Doppler UltraFast™Doppler, contrast ultrasound (CEUS), color Doppler and ultra-sensitive energy Doppler, high-performance directional energy Doppler, Elastography ShearWave™ UF-Doppler (UltraFast-Doppler) and microbubble injection (SonoVue) Apparatus for performing the UF Doppler sequence: Aixplorer, manufacturer : Supersonic Imagine, Aix-en-Provence, France, CE Marking.&#xD;
3D RCA dedicated vascular probe with dedicated Doppler sequences</description>
    <arm_group_label>Carotid plaque or stenosis ultrasound enhanced UF assesment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient is over 18&#xD;
&#xD;
          -  The patient is scheduled for carotid endarterectomy within 30 days at most&#xD;
&#xD;
          -  The patient has a social security system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-atheromatous carotid stenosis (radiation)&#xD;
&#xD;
          -  Contraindication of the use of SonoVue ultrasound contrast media. Hypersensitivity to&#xD;
             the active ingredient or any of the following excipients: Macrogol 4000;&#xD;
             Distearoylphosphatidylcholine; Dipalmitoylphosphatidylglycerol sodium; Palmitic acid.&#xD;
&#xD;
          -  The patient has any of the following conditions: right-left shunt, severe pulmonary&#xD;
             hypertension (pulmonary blood pressure &gt; 90 mm Hg), uncontrolled systemic hypertension&#xD;
             and respiratory distress syndrome.&#xD;
&#xD;
          -  Lack of social security coverage, patient under justice&#xD;
&#xD;
          -  Allergy to ultrasound gel&#xD;
&#xD;
          -  Pregnancy. (As a precautionary measure, it is best to avoid using SonoVue during&#xD;
             pregnancy according to SPC)&#xD;
&#xD;
          -  Patient under guardianship or curatorship or under the protection of justice.&#xD;
&#xD;
          -  Patient unable or unwilling to give written consent&#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>Tristan MIRAULT, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hopital europeen Georges-Pompidou</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tristan MIRAULT, MD, PhD</last_name>
    <phone>+33 (0)1.56.09.26.51</phone>
    <email>tristan.mirault@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laura LE MAO, MSc</last_name>
    <phone>+33.1.56.09.54.97</phone>
    <email>laura.le-mao@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hopital europeen Georges-Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tristan MIRAULT, MD, PhD</last_name>
      <phone>+33.1.56.09.58.32</phone>
      <email>tristan.mirault@aphp.fr</email>
    </contact>
    <contact_backup>
      <last_name>Helene MORTELETTE, PhD</last_name>
      <phone>+33.1.56.09.38.72</phone>
      <email>helene.mortelette@aphp.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Tristan MIRAULT, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lina KHIDER, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Guillaume GOUDOT, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Emmanuel MESSAS, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>November 15, 2021</last_update_submitted>
  <last_update_submitted_qc>November 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Carotid Stenosis</keyword>
  <keyword>Endarterectomy, Carotid</keyword>
  <keyword>Carotid Arteries</keyword>
  <keyword>Carotid Artery, Internal</keyword>
  <keyword>Stroke</keyword>
  <keyword>Ultrasonography</keyword>
  <keyword>Ultrasonography, Doppler</keyword>
  <keyword>diagnostic imaging</keyword>
  <keyword>Prognosis</keyword>
  <keyword>Contrast Media</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carotid Stenosis</mesh_term>
    <mesh_term>Carotid Artery Diseases</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Neovascularization, Pathologic</mesh_term>
    <mesh_term>Plaque, Atherosclerotic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data (IPD) that underlie results in publication could be shared</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data could be available one year after the last publication</ipd_time_frame>
    <ipd_access_criteria>Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team.&#xD;
Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and potentially commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.</ipd_access_criteria>
  </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/NCT04470687
org study id: APHP180482
secondary id: 2019-A03331-56
nct id: NCT04470687
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Stroke is the second leading cause of death in the Western world and the leading cause of
      major lifelong disability. About 15% of strokes are secondary to thrombosis or embolization
      of an unstable atheromatous carotid plaque. In these symptomatic patients, the degree of
      carotid stenosis is correlated with the risk of early recurrence. Patients with stenosis over
      70% are therefore offered an endarterectomy, an operation to remove carotid plaque, to
      prevent future strokes[1]. In asymptomatic patients, the degree of stenosis is a limited
      predictor, and better risk stratification is required to assess the degree of plaque
      vulnerability and stroke risk of the patient. The therapeutic decision towards endarterectomy
      in addition to drug therapy is debated because of a variable and dependent benefit/risk
      balance for each patient. A number of imaging parameters have been studied: ulceration,
      heterogeneity, vascularization of the plaque for example, but their place is not well defined
      [2].

      The usual evaluation of carotid stenosis is by conventional Doppler ultrasound with
      calculation of the degree of stenosis according to the NASCET criteria.

      For symptomatic stenoses the intervention is recommended when above 70% and is discussed from
      50% to 70% of NASCET stenosis degree.

      For asymptomatic stenoses, the procedure is discussed when above 60% taking into account the
      patient's life expectancy, the risk of the surgery and the unstable nature of the plaque [2].

      Destabilization of the carotid plaque is partially induced by inflammation associated with
      neo-vascularization. The detection of these new vessels by conventional contrast ultrasound
      has already shown a distinction between stable and unstable plaques, by the presence or
      absence of microbubbles in the plaque. However, this assessment is not very precise and only
      the most vascularized plaques can be detected. Ultrafast ultrasound Imaging is a new
      ultrasonic Imaging modality that allows detecting low speed flows, a tiny vascular structure
      within the vessel wall.

      RESEARCH HYPOTHESIS Plaques neo-vascularization would be more precisely detected and
      characterized by ultrafast imaging coupled with microbubble injection than conventional
      ultrasound imaging.

      A better assessment of plaque instability could improve the selection of patients for carotid
      endarterectomy and increase the benefit/risk ratio of this preventive surgery.
see above
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Neovascularization of the carotid plaque
time frame: end of inclusions
description: Correlation BETWEEN the average signal strength of the carotid plaque analyzed after injection of ultrasound contrast medium by three-dimensional probe with UF-Doppler AND the number of neovessels determined by histological analysis of the carotid plaque (number of neovessels per section) studied.
measure: Plaque stable or unstable
time frame: end of inclusions
description: analyzed after injection of ultrasound contrast medium by three-dimensional probe with UF-Doppler AND the plaque stability according to Oxford criteria
measure: Plaque symptomatic or not
time frame: end of inclusions
description: Comparison BETWEEN the average signal strength of the carotid plaque analyzed after injection of ultrasound contrast medium by three-dimensional probe with UF-Doppler AND the symptomatic or asymptomatic status for stroke of the patient
arm group label: Carotid plaque or stenosis ultrasound enhanced UF assesment
arm group type: Experimental
description: symptomatic or asymptomatic patients with atheromatous carotid stenosis scheduled for carotid endarterectomy
intervention type: Device
intervention name: contrast enhanced ultrafast ultrasound imaging
description: Ultrasound contrast medium: SonoVue 8µL/mL (Bracco International BV) Ultrasound scanner: Aixplorer® device marketed by SuperSonic Imagine©, CE Doppler UltraFast™Doppler, contrast ultrasound (CEUS), color Doppler and ultra-sensitive energy Doppler, high-performance directional energy Doppler, Elastography ShearWave™ UF-Doppler (UltraFast-Doppler) and microbubble injection (SonoVue) Apparatus for performing the UF Doppler sequence: Aixplorer, manufacturer : Supersonic Imagine, Aix-en-Provence, France, CE Marking.
3D RCA dedicated vascular probe with dedicated Doppler sequences
arm group label: Carotid plaque or stenosis ultrasound enhanced UF assesment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tristan MIRAULT, MD, PhD
role: Principal Investigator
affiliation: Hopital europeen Georges-Pompidou
last name: Tristan MIRAULT, MD, PhD
phone: +33 (0)1.56.09.26.51
email: tristan.mirault@aphp.fr
last name: Laura LE MAO, MSc
phone: +33.1.56.09.54.97
email: laura.le-mao@aphp.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Carotid Stenosis
mesh term: Carotid Artery Diseases
mesh term: Atherosclerosis
mesh term: Neovascularization, Pathologic
mesh term: Plaque, Atherosclerotic
sharing ipd: Yes
ipd description: Individual participant data (IPD) that underlie results in publication could be shared
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data could be available one year after the last publication
ipd access criteria: Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team.
Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and potentially commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.