<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/NCT02184117</url>
  </required_header>
  <id_info>
    <org_study_id>HSC-MS-14-0399</org_study_id>
    <nct_id>NCT02184117</nct_id>
  </id_info>
  <brief_title>CONTRAST (Can cONTrast Injection Better Approximate FFR compAred to Pure reSTing Physiology?)</brief_title>
  <acronym>CONTRAST</acronym>
  <official_title>CONTRAST (Can cONTrast Injection Better Approximate FFR compAred to Pure reSTing Physiology?)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center, Houston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Abbott Medical Devices</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Health Science Center, Houston</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the diagnostic performances of iodine contrast&#xD;
      medium and resting conditions to predict fractional flow reserve (FFR). Reference FFR will be&#xD;
      measured using standard adenosine. We hypothesize that contrast FFR will offer superior&#xD;
      diagnostic agreement compared to resting conditions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We are conducting a diagnostic accuracy study. The reference standard is adenosine-derived&#xD;
      FFR. The diagnostic tests undergoing evaluation are resting conditions and hyperemia induced&#xD;
      by intracoronary injection of contrast medium. While all these tests give a continuous&#xD;
      result, we will apply binary cutoffs for comparison to FFR≤0.8 as the reference standard.&#xD;
      Subjects will be selected prospectively from consecutive patients undergoing FFR assessment&#xD;
      for standard clinical indications. The paired comparative design means that each patient will&#xD;
      undergo resting (baseline), post-contrast, and adenosine-derived measurements. To enhance&#xD;
      test integrity, all pressure recordings will be analyzed in a central physiology core&#xD;
      laboratory blinded to clinical data and recruiting site.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</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>Agreement with binary FFR≤0.80</measure>
    <time_frame>Baseline</time_frame>
    <description>To quantify any improvement in binary agreement from resting conditions to contrast medium injection, using adenosine-derived FFR≤0.8 as the reference standard.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Binary diagnostic performance</measure>
    <time_frame>Baseline</time_frame>
    <description>To describe the diagnostic performance of resting conditions and contrast medium injection using sensitivity and specificity, positive and negative predictive value, and area under the receiver operating characteristic (ROC) curve, compared to adenosine-derived FFR≤0.8 as the reference standard.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Continuous relationship with FFR</measure>
    <time_frame>Baseline</time_frame>
    <description>To determine the relationship between adenosine-derived FFR and either resting conditions or contrast medium injection using scatter plots (correlation coefficient) and Bland-Altman analysis (bias and limits of agreement).</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">763</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>All patients</arm_group_label>
    <description>Entire cohort undergoes paired testing</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adenosine</intervention_name>
    <description>Intracoronary or intravenous adenosine to induce hyperemia for reference FFR</description>
    <arm_group_label>All patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Contrast Media</intervention_name>
    <description>Intracoronary injection of contrast medium to induce hyperemia for &quot;contrast FFR&quot;</description>
    <arm_group_label>All patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Resting conditions</intervention_name>
    <description>Baseline measurement of aortic and coronary pressures</description>
    <arm_group_label>All patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing FFR assessment for standard clinical indications&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older.&#xD;
&#xD;
          -  Undergoing FFR assessment for standard clinical indications.&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior coronary artery bypass grafting (CABG).&#xD;
&#xD;
          -  Extremely tortuous or calcified coronary arteries precluding intracoronary physiologic&#xD;
             measurements. Operators may exclude subtotal or similar high-grade lesions, which in&#xD;
             their judgment may be threatened by pressure wire placement.&#xD;
&#xD;
          -  Known severe left ventricular hypertrophy (septal wall thickness at echocardiography&#xD;
             of &gt;13 mm).&#xD;
&#xD;
          -  Inability to receive adenosine (for example, severe reactive airway disease, marked&#xD;
             hypotension, or advanced atrioventricular block without pacemaker).&#xD;
&#xD;
          -  Recent (within 3 weeks prior to cardiac catheterization) ST-segment elevation&#xD;
             myocardial infarction (STEMI) in any arterial distribution (not specifically target&#xD;
             lesion).&#xD;
&#xD;
          -  Culprit lesions (based on clinical judgment of the operator) for either STEMI or&#xD;
             non-STEMI cannot be included.&#xD;
&#xD;
          -  Severe cardiomyopathy (ejection fraction &lt;30%).&#xD;
&#xD;
          -  Renal insufficiency such that an additional 12 to 20 mL of contrast would, in the&#xD;
             opinion of the operator, pose unwarranted risk to the patient.&#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>Nils P Johnson, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Medical School at Houston</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William F Fearon, MD</last_name>
    <role>Study Director</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University, Palo Alto VA</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Integris Health</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Center (OLV-Ziekenhuis)</name>
      <address>
        <city>Aalst</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Louis Pradel</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Naples Federico II</name>
      <address>
        <city>Naples</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catharina Hospital</name>
      <address>
        <city>Eindhoven</city>
        <state>Noord-Brabant</state>
        <zip>5623EJ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Fernando Fonseca</name>
      <address>
        <city>Lisbon</city>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Södersjukhuset</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Golden Jubilee National Hospital</name>
      <address>
        <city>Clydebank</city>
        <zip>G81 4HX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>De Bruyne B, Pijls NH, Barbato E, Bartunek J, Bech JW, Wijns W, Heyndrickx GR. Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation. 2003 Apr 15;107(14):1877-83. doi: 10.1161/01.CIR.0000061950.24940.88. Epub 2003 Mar 31.</citation>
    <PMID>12668522</PMID>
  </reference>
  <results_reference>
    <citation>Johnson NP, Jeremias A, Zimmermann FM, Adjedj J, Witt N, Hennigan B, Koo BK, Maehara A, Matsumura M, Barbato E, Esposito G, Trimarco B, Rioufol G, Park SJ, Yang HM, Baptista SB, Chrysant GS, Leone AM, Berry C, De Bruyne B, Gould KL, Kirkeeide RL, Oldroyd KG, Pijls NHJ, Fearon WF. Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment. JACC Cardiovasc Interv. 2016 Apr 25;9(8):757-767. doi: 10.1016/j.jcin.2015.12.273.</citation>
    <PMID>27101902</PMID>
  </results_reference>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 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 16, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Texas Health Science Center, Houston</investigator_affiliation>
    <investigator_full_name>Nils Johnson</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Fractional Flow Reserve, Myocardial</keyword>
  <keyword>Adenosine</keyword>
  <keyword>Contrast Media</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenosine</mesh_term>
  </intervention_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/NCT02184117
org study id: HSC-MS-14-0399
nct id: NCT02184117
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to determine the diagnostic performances of iodine contrast
      medium and resting conditions to predict fractional flow reserve (FFR). Reference FFR will be
      measured using standard adenosine. We hypothesize that contrast FFR will offer superior
      diagnostic agreement compared to resting conditions.
We are conducting a diagnostic accuracy study. The reference standard is adenosine-derived
      FFR. The diagnostic tests undergoing evaluation are resting conditions and hyperemia induced
      by intracoronary injection of contrast medium. While all these tests give a continuous
      result, we will apply binary cutoffs for comparison to FFR≤0.8 as the reference standard.
      Subjects will be selected prospectively from consecutive patients undergoing FFR assessment
      for standard clinical indications. The paired comparative design means that each patient will
      undergo resting (baseline), post-contrast, and adenosine-derived measurements. To enhance
      test integrity, all pressure recordings will be analyzed in a central physiology core
      laboratory blinded to clinical data and recruiting site.
observational model: Cohort
time perspective: Prospective
measure: Agreement with binary FFR≤0.80
time frame: Baseline
description: To quantify any improvement in binary agreement from resting conditions to contrast medium injection, using adenosine-derived FFR≤0.8 as the reference standard.
measure: Binary diagnostic performance
time frame: Baseline
description: To describe the diagnostic performance of resting conditions and contrast medium injection using sensitivity and specificity, positive and negative predictive value, and area under the receiver operating characteristic (ROC) curve, compared to adenosine-derived FFR≤0.8 as the reference standard.
measure: Continuous relationship with FFR
time frame: Baseline
description: To determine the relationship between adenosine-derived FFR and either resting conditions or contrast medium injection using scatter plots (correlation coefficient) and Bland-Altman analysis (bias and limits of agreement).
arm group label: All patients
description: Entire cohort undergoes paired testing
intervention type: Drug
intervention name: Adenosine
description: Intracoronary or intravenous adenosine to induce hyperemia for reference FFR
arm group label: All patients
intervention type: Drug
intervention name: Contrast Media
description: Intracoronary injection of contrast medium to induce hyperemia for "contrast FFR"
arm group label: All patients
intervention type: Drug
intervention name: Resting conditions
description: Baseline measurement of aortic and coronary pressures
arm group label: All patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nils P Johnson, MD, MS
role: Principal Investigator
affiliation: University of Texas Medical School at Houston
last name: William F Fearon, MD
role: Study Director
affiliation: Stanford University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
country: Italy
country: Korea, Republic of
country: Netherlands
country: Portugal
country: Sweden
country: United Kingdom
country: United States
citation: De Bruyne B, Pijls NH, Barbato E, Bartunek J, Bech JW, Wijns W, Heyndrickx GR. Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation. 2003 Apr 15;107(14):1877-83. doi: 10.1161/01.CIR.0000061950.24940.88. Epub 2003 Mar 31.
PMID: 12668522
citation: Johnson NP, Jeremias A, Zimmermann FM, Adjedj J, Witt N, Hennigan B, Koo BK, Maehara A, Matsumura M, Barbato E, Esposito G, Trimarco B, Rioufol G, Park SJ, Yang HM, Baptista SB, Chrysant GS, Leone AM, Berry C, De Bruyne B, Gould KL, Kirkeeide RL, Oldroyd KG, Pijls NHJ, Fearon WF. Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment. JACC Cardiovasc Interv. 2016 Apr 25;9(8):757-767. doi: 10.1016/j.jcin.2015.12.273.
PMID: 27101902
responsible party type: Principal Investigator
investigator affiliation: The University of Texas Health Science Center, Houston
investigator full name: Nils Johnson
investigator title: Associate Professor of Medicine
mesh term: Coronary Artery Disease
mesh term: Adenosine