<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/NCT04420325</url>
  </required_header>
  <id_info>
    <org_study_id>S63740</org_study_id>
    <nct_id>NCT04420325</nct_id>
  </id_info>
  <brief_title>COronary and MICrocirculatory Measurements in Patients With Aortic Valve Stenosis.</brief_title>
  <acronym>COMIC-AS</acronym>
  <official_title>COronary and MICrocirculatory Measurements in Patients With Aortic Valve, the COMIC AS Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AZ Delta</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Antwerp</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</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>
      Although concomitant coronary artery disease (CAD) is frequent in patients with severe aortic&#xD;
      stenosis (AS), hemodynamic assessment of CAD severity in patients undergoing valve&#xD;
      replacement for severe AS is challenging. Myocardial hypertrophic remodeling interferes with&#xD;
      coronary blood flow and may influence the values of fractional flow reserve (FFR) and&#xD;
      nonhyperemic pressure ratios (NHPRs). The aim of the current study is to investigate the&#xD;
      effect of the AS and its treatment on current indices used for evaluation of CAD. The&#xD;
      investigators will compare intracoronary hemodynamics before, immediately after, and 6 mo&#xD;
      after aortic valve replacement (AVR) when it is expected that microvascular function has&#xD;
      improved. Furthermore, the investigators will compare FFR and resting full-cycle ratio (RFR)&#xD;
      with myocardial perfusion single-photon emission-computed tomography (SPECT) as indicators of&#xD;
      myocardial ischemia in patients with AS and CAD. One-hundred consecutive patients with AS and&#xD;
      intermediate CAD will be prospectively included. Patients will undergo pre-AVR SPECT and&#xD;
      intracoronary hemodynamic assessment at baseline, immediately after valve replacement [if&#xD;
      transcatheter AVR (TAVR) is chosen], and 6 mo after AVR. The primary end point is the change&#xD;
      in FFR 6 mo after AVR. Secondary end points include the acute change of FFR after TAVR, the&#xD;
      diagnostic accuracy of FFR versus RFR compared with SPECT for the assessment of ischemia,&#xD;
      changes in microvascular function as assessed by the index of microcirculatory resistance&#xD;
      (IMR), and the effect of these changes on FFR. The present study will evaluate intracoronary&#xD;
      hemodynamic parameters before, immediately after, and 6 mo after AVR in patients with AS and&#xD;
      intermediate coronary stenosis. The understanding of the impact of AVR on the assessment of&#xD;
      FFR, NHPR, and microvascular function may help guide the need for revascularization in&#xD;
      patients with AS and CAD planned for AVR.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">May 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</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>FFR 6 months after SAVR/TAVI.</measure>
    <time_frame>6 months</time_frame>
    <description>Aortic valve intervention can potentially result in a change in fractional flow reserve (FFR) 6 months after SAVR/TAVI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>IMR 6 months after SAVR/TAVI.</measure>
    <time_frame>6 months</time_frame>
    <description>Measurement of IMR in patients with AS prior to intervention and 6 months after TAVI/SAVR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FFR versus RFR to determine ischemia.</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of the diagnostic performance of FFR versus RFR compared with SPECT ischemia.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Aortic Stenosis</condition>
  <condition>Coronary Artery Disease</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Before IMR measurement, a peripheral blood sample (10cc EDTA, citrate and 2.5mL PaxGene® RNA&#xD;
      tube) will be obtained to assess platelet function and for biomarker evaluation (RNA&#xD;
      analysis).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing routine cardiac catheterization during preparation for TAVI or SAVR,&#xD;
        who are found to have coronary artery disease, will be approached to take part.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Patient undergoing the procedure is older than 18 years, has severe aortic valve&#xD;
             stenosis (according to ESC guidelines) and is planned for cardiac catheterization as&#xD;
             part of the pre-operative (SAVR) or pre-percutaneous (TAVI) work up.&#xD;
&#xD;
             2. The patient has an intermediate (50-90%) coronary lesion that requires further&#xD;
             evaluation.&#xD;
&#xD;
             3. The patient undergoing the procedure is male, or if female, has no childbearing&#xD;
             potential or is not pregnant.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The procedure is an emergency and/or the patient is unstable.&#xD;
&#xD;
          2. Pregnancy or lactation&#xD;
&#xD;
          3. Haemodynamically unstable patients&#xD;
&#xD;
          4. Killip class III-IV heart failure&#xD;
&#xD;
          5. Previous coronary artery by-pass in the artery being assessed&#xD;
&#xD;
          6. Contra-indications for adenosine administration: severe asthma or pre-existing type 2&#xD;
             AV-block&#xD;
&#xD;
          7. No significant coronary artery disease (&lt;50% stenosis on angiography).&#xD;
&#xD;
          8. Critical coronary artery disease deemed by the Heart Team to require immediate&#xD;
             revascularization&#xD;
&#xD;
          9. Patients will be excluded from the SPECT study (secondary objective) if they have a&#xD;
             left main coronary stenosis &gt;50%, triple vessel disease, previous myocardial&#xD;
             infarction in the same coronary artery &amp; tandem lesions (separated by &gt;10mm) requiring&#xD;
             independent evaluation in the same coronary artery since these factors interfere with&#xD;
             the SPECT analysis.&#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>Christophe Dubois, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UZ Leuven</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Karin R Broos</last_name>
    <phone>+3216342465</phone>
    <phone_ext>+32468312267</phone_ext>
    <email>karin.broos@uzleuven.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lennert Minten, MD</last_name>
    <phone>+32 16 34 59 14</phone>
    <email>Lennert.minten@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams-brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sabine Van Roey</last_name>
      <phone>+32 16 34 24 66</phone>
      <email>sabine.vanroey@uzleuven.be</email>
    </contact>
    <investigator>
      <last_name>Lennert Minten, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University hospital Antwerp</name>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vincent Segers, MD, PhD</last_name>
      <email>Vincent.Segers@uza.be</email>
    </contact>
    <investigator>
      <last_name>Vincent Segers, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>AZ Delta</name>
      <address>
        <city>Roeselare</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maarten Vanhaverbeke, MD, PhD</last_name>
      <email>Maarten.Vanhaverbeke@azdelta.be</email>
    </contact>
    <investigator>
      <last_name>Maarten Vanhaverbeke, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>November 8, 2022</last_update_submitted>
  <last_update_submitted_qc>November 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</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>Coronary Artery Disease</mesh_term>
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04420325
org study id: S63740
nct id: NCT04420325
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Although concomitant coronary artery disease (CAD) is frequent in patients with severe aortic
      stenosis (AS), hemodynamic assessment of CAD severity in patients undergoing valve
      replacement for severe AS is challenging. Myocardial hypertrophic remodeling interferes with
      coronary blood flow and may influence the values of fractional flow reserve (FFR) and
      nonhyperemic pressure ratios (NHPRs). The aim of the current study is to investigate the
      effect of the AS and its treatment on current indices used for evaluation of CAD. The
      investigators will compare intracoronary hemodynamics before, immediately after, and 6 mo
      after aortic valve replacement (AVR) when it is expected that microvascular function has
      improved. Furthermore, the investigators will compare FFR and resting full-cycle ratio (RFR)
      with myocardial perfusion single-photon emission-computed tomography (SPECT) as indicators of
      myocardial ischemia in patients with AS and CAD. One-hundred consecutive patients with AS and
      intermediate CAD will be prospectively included. Patients will undergo pre-AVR SPECT and
      intracoronary hemodynamic assessment at baseline, immediately after valve replacement [if
      transcatheter AVR (TAVR) is chosen], and 6 mo after AVR. The primary end point is the change
      in FFR 6 mo after AVR. Secondary end points include the acute change of FFR after TAVR, the
      diagnostic accuracy of FFR versus RFR compared with SPECT for the assessment of ischemia,
      changes in microvascular function as assessed by the index of microcirculatory resistance
      (IMR), and the effect of these changes on FFR. The present study will evaluate intracoronary
      hemodynamic parameters before, immediately after, and 6 mo after AVR in patients with AS and
      intermediate coronary stenosis. The understanding of the impact of AVR on the assessment of
      FFR, NHPR, and microvascular function may help guide the need for revascularization in
      patients with AS and CAD planned for AVR.
observational model: Cohort
time perspective: Prospective
measure: FFR 6 months after SAVR/TAVI.
time frame: 6 months
description: Aortic valve intervention can potentially result in a change in fractional flow reserve (FFR) 6 months after SAVR/TAVI.
measure: IMR 6 months after SAVR/TAVI.
time frame: 6 months
description: Measurement of IMR in patients with AS prior to intervention and 6 months after TAVI/SAVR.
measure: FFR versus RFR to determine ischemia.
time frame: Baseline
description: Comparison of the diagnostic performance of FFR versus RFR compared with SPECT ischemia.
Before IMR measurement, a peripheral blood sample (10cc EDTA, citrate and 2.5mL PaxGene® RNA
      tube) will be obtained to assess platelet function and for biomarker evaluation (RNA
      analysis).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christophe Dubois, MD, PhD
role: Principal Investigator
affiliation: UZ Leuven
last name: Karin R Broos
phone: +3216342465
phone ext: +32468312267
email: karin.broos@uzleuven.be
last name: Lennert Minten, MD
phone: +32 16 34 59 14
email: Lennert.minten@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Belgium
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Aortic Valve Stenosis
mesh term: Constriction, Pathologic
sharing ipd: Undecided