<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/NCT02264717</url>
  </required_header>
  <id_info>
    <org_study_id>Dan-NICAD</org_study_id>
    <nct_id>NCT02264717</nct_id>
  </id_info>
  <brief_title>Dan-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease</brief_title>
  <official_title>Dan-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      1. The primary purpose of this study is to determine the diagnostic accuracy of the CADscore&#xD;
      System, a new danish technology that records sounds from turbulence of bloodflow in the&#xD;
      coronary vessels.&#xD;
&#xD;
      And secondary:&#xD;
&#xD;
        1. To determine the accuracy of cardiac magnetic resonance imaging (MRI) and single-photon&#xD;
           emission computed tomography (SPECT), as secondary tests after detection of obstructive&#xD;
           anatomic coronary artery stenosis by coronary computed tomographic angiography (CCTA).&#xD;
&#xD;
        2. To examine the patient population for bio-genetic markers related to development of&#xD;
           arteriosclerosis.&#xD;
&#xD;
        3. To evaluate virtual fractional flow reserve (vFFR) computed from coronary angiograms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary study CCTA is currently the first choice to rule out coronary artery disease (CAD) in&#xD;
      patients with typical or atypical chest pain. 4500 patients are annually examined with CCTA,&#xD;
      in the Central Jutland Region of Denmark, and approximately 80% are discharged after ruling&#xD;
      out CAD. CCTA is a diagnostic scan that exposes the patients to radiation, therefore a better&#xD;
      risk stratification prior to the test is desirable. The CADscore is a newly developed danish&#xD;
      technology that has been tested so far in 1000 patients. An area under the curve of the&#xD;
      receiver operating characteristic (AUC of ROC) of 75-80 has been determined compared to&#xD;
      conventional coronary angiography using quantitative coronary angiography (CCA-QCA). This&#xD;
      indicates that the CADscore could potentially be used to diagnose CAD as a supplement or risk&#xD;
      stratification prior to CCTA.&#xD;
&#xD;
      We aim to evaluate the CADscore in a large clinical trial including 2000 patients that by&#xD;
      clinical indication undergo cCTA. After cCTA approximately 20 % (400 patients) will need&#xD;
      evaluation by CCA with FFR. CADscore results will be compared to CCTA and CCA-QCA. Secondary,&#xD;
      the CADscore will be compared to the results of CCA-FFR and perfusion scans, Cardiac-MRI and&#xD;
      SPECT.&#xD;
&#xD;
      Substudies&#xD;
&#xD;
        1. Perfusion scans&#xD;
&#xD;
           CCTA demonstrates good diagnostic performance for detection and exclusion of anatomic&#xD;
           coronary artery stenosis, but several studies have previously shown that CCTA has a low&#xD;
           positive predictive value for identification of hemodynamically significant CAD. This&#xD;
           emphasizes the need for additional tests to evaluate the severity (or exclusion) of&#xD;
           hemodynamically significant CAD. Measurement of FFR during CCA represents the &quot;gold&#xD;
           standard&quot; for assessment of the hemodynamic significance of coronary artery stenosis.&#xD;
           The disadvantage of CCA with FFR is that it is an invasive procedure.&#xD;
&#xD;
           After cCTA approximately 20 % (400 patients) will need further testing and that group of&#xD;
           patients will be randomized to either Cardiac MRI or SPECT followed by CCA with FFR.&#xD;
&#xD;
           The substudy aims to evaluate the diagnostic accuracy of perfusion imaging (Cardiac MRI&#xD;
           and SPECT) compared with CCA with FFR.&#xD;
&#xD;
        2. Virtual FFR&#xD;
&#xD;
      The accuracy and precision of virtual-FFR compared with conventional FFR will be determined.&#xD;
      Virtual FFR is computed from the coronary angiogram using computational fluid dynamics.&#xD;
      Subjects with diameter stenosis in the range of 30 to 90% by visual estimate in one or more&#xD;
      vessel segments with reference diameter ≥2.0 mm will be included in the analysis. FFR is the&#xD;
      reference standard to determine the presence or absence of hemodynamically significant&#xD;
      obstruction with a cut-off value of 0.80. Computation of vFFR with and without hyperaemia&#xD;
      will be compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnostic accuracy of the CADscore system compared to CCTA and CCA-QCA.</measure>
    <time_frame>Within one week before or after CCTA</time_frame>
    <description>Diagnostic precision will be evaluated as the AUC-ROC. The CADscore will be dichotomized at cut off values of 20,25 and 30 and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. The CADscore system operates with 3 intervals of risk stratification: &lt;20, 20-30, &gt;30 (low, intermedia and high risk of cardio vascular disease, respectively) Obstructive CAD is defined as ≥ 50% diameter stenosis as determined by quantitative analysis of CCA (QCA). Non-Obstructive CAD is defined as no detection of obstructive anatomic coronary artery stenosis by CCTA or stenosis detected by CCTA combined with a evaluation by CCA-QCA demonstrating a luminal stenosis diameter &lt; 50 %.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of CADScore Safety of CADScore</measure>
    <time_frame>One week after the use of CADScore</time_frame>
    <description>Registration of adverse events related to the use of CADScore</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic accuracy of the CADScore system compared to CCA-FFR.</measure>
    <time_frame>Within four weeks after CADScore</time_frame>
    <description>Diagnostic precision will be evaluated as the AUC-ROC and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy.&#xD;
CAD is defined as CCA-FFR under 0.80.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feasibility of virtual FFR</measure>
    <time_frame>one day</time_frame>
    <description>Feasibility of vFFR compared to conventional FFR assessed as fraction of conventional FFR measurements where a vFFR values is computed by the core lab.</description>
  </other_outcome>
  <other_outcome>
    <measure>Diagnostic accuracy of virtual FFR</measure>
    <time_frame>one day</time_frame>
    <description>Diagnostic accuracy of vFFR as the area under the receiver operating characteristic curve (AUC by ROC). The performance of vFFR in predicting functionally significant stenosis is assessed with and without hyperaemia using sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy, together with their 95% confidence intervals.</description>
  </other_outcome>
  <other_outcome>
    <measure>The diagnostic accuracy of perfusion imaging (Cardiac MRI and SPECT)</measure>
    <time_frame>Within 4 weeks after the CCTA</time_frame>
    <description>Diagnostic performance will be evaluated as the AUC-ROC, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy.&#xD;
CAD is defined as a CCA-FFR below 0,80. A Chi2 test will be used to compare SPECT and Cardiac-MRI.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1676</enrollment>
  <condition>Angina Pectoris</condition>
  <condition>Arteriosclerosis</condition>
  <condition>Coronary Artery Disease</condition>
  <condition>Myocardial Ischemia</condition>
  <arm_group>
    <arm_group_label>Cardiac MRi</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A minimum of 150 patients will be randomized to Cardiac MRI followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPECT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A minimum 150 patients will be randomized to SPECT followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>SPECT</intervention_name>
    <description>Patients are randomized to either SPECT or Cardiac MRI</description>
    <arm_group_label>SPECT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cardiac MRI</intervention_name>
    <description>Patients are randomized to either SPECT or Cardiac MR</description>
    <arm_group_label>Cardiac MRi</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Indication for Cardiac CT&#xD;
&#xD;
          -  Signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age under 40&#xD;
&#xD;
          -  Pregnant, potentially pregnant or breast feeding&#xD;
&#xD;
          -  Contraindication for adenosine (severe asthma, clinical aortic stenosis)&#xD;
&#xD;
          -  Reduced kidney function (eGFR &lt; 40 ml/min)&#xD;
&#xD;
          -  Contraindication for MRI&#xD;
&#xD;
          -  Previous history of allergy to contrast&#xD;
&#xD;
          -  Previous revascularisation procedure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Morten Bøttcher, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Regional Hospital of Herning, department of cardiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <state>Region Midtjylland</state>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Hospital of Herning</name>
      <address>
        <city>Herning</city>
        <state>Region Midtjylland</state>
        <zip>7400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Hospital of Silkeborg</name>
      <address>
        <city>Silkeborg</city>
        <state>Region Midtjylland</state>
        <zip>8600</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>May 12, 2016</last_update_submitted>
  <last_update_submitted_qc>May 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 13, 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>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Angina Pectoris</mesh_term>
    <mesh_term>Arteriosclerosis</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_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/NCT02264717
org study id: Dan-NICAD
nct id: NCT02264717
lead sponsor: 
has dmc: Yes
1. The primary purpose of this study is to determine the diagnostic accuracy of the CADscore
      System, a new danish technology that records sounds from turbulence of bloodflow in the
      coronary vessels.

      And secondary:

        1. To determine the accuracy of cardiac magnetic resonance imaging (MRI) and single-photon
           emission computed tomography (SPECT), as secondary tests after detection of obstructive
           anatomic coronary artery stenosis by coronary computed tomographic angiography (CCTA).

        2. To examine the patient population for bio-genetic markers related to development of
           arteriosclerosis.

        3. To evaluate virtual fractional flow reserve (vFFR) computed from coronary angiograms.
Primary study CCTA is currently the first choice to rule out coronary artery disease (CAD) in
      patients with typical or atypical chest pain. 4500 patients are annually examined with CCTA,
      in the Central Jutland Region of Denmark, and approximately 80% are discharged after ruling
      out CAD. CCTA is a diagnostic scan that exposes the patients to radiation, therefore a better
      risk stratification prior to the test is desirable. The CADscore is a newly developed danish
      technology that has been tested so far in 1000 patients. An area under the curve of the
      receiver operating characteristic (AUC of ROC) of 75-80 has been determined compared to
      conventional coronary angiography using quantitative coronary angiography (CCA-QCA). This
      indicates that the CADscore could potentially be used to diagnose CAD as a supplement or risk
      stratification prior to CCTA.

      We aim to evaluate the CADscore in a large clinical trial including 2000 patients that by
      clinical indication undergo cCTA. After cCTA approximately 20 % (400 patients) will need
      evaluation by CCA with FFR. CADscore results will be compared to CCTA and CCA-QCA. Secondary,
      the CADscore will be compared to the results of CCA-FFR and perfusion scans, Cardiac-MRI and
      SPECT.

      Substudies

        1. Perfusion scans

           CCTA demonstrates good diagnostic performance for detection and exclusion of anatomic
           coronary artery stenosis, but several studies have previously shown that CCTA has a low
           positive predictive value for identification of hemodynamically significant CAD. This
           emphasizes the need for additional tests to evaluate the severity (or exclusion) of
           hemodynamically significant CAD. Measurement of FFR during CCA represents the "gold
           standard" for assessment of the hemodynamic significance of coronary artery stenosis.
           The disadvantage of CCA with FFR is that it is an invasive procedure.

           After cCTA approximately 20 % (400 patients) will need further testing and that group of
           patients will be randomized to either Cardiac MRI or SPECT followed by CCA with FFR.

           The substudy aims to evaluate the diagnostic accuracy of perfusion imaging (Cardiac MRI
           and SPECT) compared with CCA with FFR.

        2. Virtual FFR

      The accuracy and precision of virtual-FFR compared with conventional FFR will be determined.
      Virtual FFR is computed from the coronary angiogram using computational fluid dynamics.
      Subjects with diameter stenosis in the range of 30 to 90% by visual estimate in one or more
      vessel segments with reference diameter ≥2.0 mm will be included in the analysis. FFR is the
      reference standard to determine the presence or absence of hemodynamically significant
      obstruction with a cut-off value of 0.80. Computation of vFFR with and without hyperaemia
      will be compared.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Investigator)
measure: Diagnostic accuracy of the CADscore system compared to CCTA and CCA-QCA.
time frame: Within one week before or after CCTA
description: Diagnostic precision will be evaluated as the AUC-ROC. The CADscore will be dichotomized at cut off values of 20,25 and 30 and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. The CADscore system operates with 3 intervals of risk stratification: <20, 20-30, >30 (low, intermedia and high risk of cardio vascular disease, respectively) Obstructive CAD is defined as ≥ 50% diameter stenosis as determined by quantitative analysis of CCA (QCA). Non-Obstructive CAD is defined as no detection of obstructive anatomic coronary artery stenosis by CCTA or stenosis detected by CCTA combined with a evaluation by CCA-QCA demonstrating a luminal stenosis diameter < 50 %.
measure: Safety of CADScore Safety of CADScore
time frame: One week after the use of CADScore
description: Registration of adverse events related to the use of CADScore
measure: Diagnostic accuracy of the CADScore system compared to CCA-FFR.
time frame: Within four weeks after CADScore
description: Diagnostic precision will be evaluated as the AUC-ROC and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy.
CAD is defined as CCA-FFR under 0.80.
measure: Feasibility of virtual FFR
time frame: one day
description: Feasibility of vFFR compared to conventional FFR assessed as fraction of conventional FFR measurements where a vFFR values is computed by the core lab.
measure: Diagnostic accuracy of virtual FFR
time frame: one day
description: Diagnostic accuracy of vFFR as the area under the receiver operating characteristic curve (AUC by ROC). The performance of vFFR in predicting functionally significant stenosis is assessed with and without hyperaemia using sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy, together with their 95% confidence intervals.
measure: The diagnostic accuracy of perfusion imaging (Cardiac MRI and SPECT)
time frame: Within 4 weeks after the CCTA
description: Diagnostic performance will be evaluated as the AUC-ROC, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy.
CAD is defined as a CCA-FFR below 0,80. A Chi2 test will be used to compare SPECT and Cardiac-MRI.
arm group label: Cardiac MRi
arm group type: Active Comparator
description: A minimum of 150 patients will be randomized to Cardiac MRI followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA)
arm group label: SPECT
arm group type: Active Comparator
description: A minimum 150 patients will be randomized to SPECT followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA).
intervention type: Procedure
intervention name: SPECT
description: Patients are randomized to either SPECT or Cardiac MRI
arm group label: SPECT
intervention type: Procedure
intervention name: Cardiac MRI
description: Patients are randomized to either SPECT or Cardiac MR
arm group label: Cardiac MRi
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Morten Bøttcher, MD, Ph.D
role: Principal Investigator
affiliation: Regional Hospital of Herning, department of cardiology
facility: 
facility: 
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Angina Pectoris
mesh term: Arteriosclerosis
mesh term: Ischemia
sharing ipd: No