<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/NCT01710254</url>
  </required_header>
  <id_info>
    <org_study_id>REGA-12F08</org_study_id>
    <nct_id>NCT01710254</nct_id>
  </id_info>
  <brief_title>Regadenoson Stress-MRI to Identify Coronary Artery Disease in Atrial Fibrillation Patients</brief_title>
  <acronym>RECAD-AF</acronym>
  <official_title>Detection of Coronary Artery Disease in Patients With Atrial Fibrillation Using Regadenoson Stress MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Atrial fibrillation (AF) is growing into an epidemic affecting 1 in 4 adults. There is a need&#xD;
      for research to elucidate the prevalence of ischemic cardiomyopathy in patients diagnosed&#xD;
      with AF. The objective of this study is to demonstrate the utility of MRI in assessment of&#xD;
      coronary artery disease. The specific objective is to demonstrate sensitivity/specificity&#xD;
      comparable to that reported in meta-analyses of non-AF patients and adenosine (90% /80%) in&#xD;
      an AF population using the time-efficient vasodilator regadenoson that requires only a single&#xD;
      intravenous (IV).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Scientific Background/Rationale:&#xD;
&#xD;
      Atrial fibrillation (AF) is a large and growing healthcare problem worldwide. Over 7 million&#xD;
      people in the U.S. and Europe currently suffer from atrial fibrillation, and this number is&#xD;
      expected to double before 2050. The lifetime risk of AF is high: ~24% at age 40, and this&#xD;
      risk remains fairly constant at older ages, with 22% lifetime risk at age 80 [1]. AF&#xD;
      significantly increases the risk of stroke and mortality, and can greatly limit quality of&#xD;
      life. Little research has been done on AF and ischemic cardiomyopathy, though it is a&#xD;
      relatively common co-morbidity. CT found increased prevalence (41% vs 27%) of coronary artery&#xD;
      disease (CAD) in patients with AF compared to patients with similar pre-test risk but no AF&#xD;
      [2]. AF patients with a positive SPECT scan for CAD have a worse prognosis for cardiac events&#xD;
      than patients with positive SPECT but without AF [3]. It was recently reported that in a&#xD;
      study of 253 AF patients, that AF patients with positive SPECT studies had a very high number&#xD;
      of false positives - only 15% of patients had significant CAD by angiography (compared to 67%&#xD;
      in the control group) [4, 5]. Just over half of the patients were in sinus rhythm at SPECT,&#xD;
      but since similar numbers of positives were seen in each half, the authors did not feel that&#xD;
      imaging during AF was the cause of the poor specificity.&#xD;
&#xD;
      Use of MRI for assessment of CAD is a growing area that entails no radiation exposure to the&#xD;
      patient. Advances in MRI have made it possible to accurately detect CAD, either as well or&#xD;
      better than SPECT in unselected populations [6, 7]. However, adoption of MRI myocardial&#xD;
      perfusion scans has been limited in part due to the challenges associated with the use of&#xD;
      adenosine. Adenosine requires starting a second IV, and to use either a special expensive&#xD;
      MRI-compatible infusion pump to deliver the drug, or long lengths of tubing to run to a pump&#xD;
      outside the scanner room. Neither solution is ideal, and regadenoson would not require any&#xD;
      such pumps or the starting of a second IV. Here the investigators propose to determine the&#xD;
      sensitivity/specificity for dynamic contrast-enhanced myocardial perfusion MRI with the&#xD;
      vasodilator regadenoson in a subpopulation of patients - those with atrial fibrillation.&#xD;
&#xD;
      The investigators have a great deal of experience with stress and rest myocardial perfusion&#xD;
      MRI. In a preliminary study imaging three patients with AF that then went to X-ray&#xD;
      angiography (cath), two of the three subjects had significant stenoses by cath, and one did&#xD;
      not. This agreed with the regadenoson stress perfusion MRI findings. These MRI acquisitions&#xD;
      were performed on a Siemens Verio MRI scanner. The Verio operates at twice the magnetic field&#xD;
      strength (3 Tesla, or 3T) of most MRI scanners, which operate at 1.5T. The higher magnetic&#xD;
      field offers images with significantly less noise (almost twice the signal-to-noise ratio).&#xD;
&#xD;
      Objective: To demonstrate sensitivity/specificity comparable to that reported in&#xD;
      meta-analyses of non-AF patients and adenosine (90%/80% [6, 7]), in an atrial fibrillation&#xD;
      population while using the time-efficient vasodilator regadenoson that requires only a single&#xD;
      IV.&#xD;
&#xD;
      Study Design: This will be a prospective, open-label, comparative trial using MRI.&#xD;
      Non-invasive MRI measurements of resting flow and flow at regadenoson stress will be obtained&#xD;
      in each subject during a one hour MRI exam using our advanced MRI acquisition techniques.&#xD;
      Sensitivity/specificity of regadenoson stress MRI will be determined using x-ray angiography&#xD;
      as the standard. X-ray angiography will be done as standard-of-care, and is not an&#xD;
      intervention of this clinical trial.&#xD;
&#xD;
      Study Procedure: Each subject will undergo a single MRI scanning session. Caffeine will be&#xD;
      stopped 12 hours prior to the procedure. One IV will be started and subjects positioned in&#xD;
      the scanner. Resting perfusion with Multihance Gd-BOPTA contrast agent will be performed&#xD;
      first. The perfusion acquisition acquires 3-6 short axis slices each heartbeat and lasts for&#xD;
      one minute. Then a standard regadenoson injection of 400ug/5cc will be given and MR imaging&#xD;
      performed with a Gd-BOPTA contrast agent bolus 60-100 seconds later [9] [10].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">October 2016</primary_completion_date>
  <phase>Phase 2</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>Sensitivity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</measure>
    <time_frame>one MRI, up to 1 hour</time_frame>
    <description>Determination of sensitivity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specificity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</measure>
    <time_frame>one MRI, up to 1 hour</time_frame>
    <description>Determination of specificity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Accuracy of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</measure>
    <time_frame>one MRI, up to 1 hour</time_frame>
    <description>Determination of accuracy of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Accuracy is the percentage of correctly classified subjects (true positive + true negative) among all subjects (true positive + true negative + false positive + false negative). Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Regadenoson MRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with AF receiving regadenoson stress MRI, using Gadobenate dimeglumine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regadenoson MRI</intervention_name>
    <description>AF patients will be provided with a regadenoson stress MRI to see if coronary artery disease can be detected with more sensitivity /specificity.</description>
    <arm_group_label>Regadenoson MRI</arm_group_label>
    <other_name>Lexiscan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gadobenate dimeglumine</intervention_name>
    <description>Resting perfusion with Multihance Gd-BOPTA contrast agent will be performed first, then a regadenoson injection will be given and MR imaging performed with a Gd-BOPTA contrast agent bolus 60-100 seconds later.</description>
    <arm_group_label>Regadenoson MRI</arm_group_label>
    <other_name>Gd-BOPTA</other_name>
    <other_name>Multihance</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with confirmed persistent or paroxysmal AF and suspected coronary artery disease&#xD;
        who will undergo catheterization X-ray angiography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Critically ill patients, patients on ventilators patients with hypotension,&#xD;
             asthmatics, and other patients whose medical care or safety may be compromised from&#xD;
             undergoing an MRI examination will be excluded.&#xD;
&#xD;
          2. Patients with claustrophobia will also be excluded since MRI is conducted in a closed&#xD;
             environment.&#xD;
&#xD;
          3. Patients with contraindications to MRI (pacemaker, metal implants).&#xD;
&#xD;
          4. Pregnant subjects (or women who may become pregnant), minors, and prisoners will be&#xD;
             excluded from this study.&#xD;
&#xD;
          5. Subjects are over 60 or have any suspicion of abnormal kidney function (a blood test&#xD;
             to determine Glomerular filtration rate (GFR) will be performed prior to imaging.&#xD;
             Subjects with GFR&lt;30 will be excluded from the study. This is standard practice for&#xD;
             clinical scans in Radiology due to the extremely small but not negligible relationship&#xD;
             between gadolinium contrast agent and nephrogenic systemic fibrosis in patients with&#xD;
             severely impaired renal function.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brent Wilson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004 Aug 31;110(9):1042-6. doi: 10.1161/01.CIR.0000140263.20897.42. Epub 2004 Aug 16.</citation>
    <PMID>15313941</PMID>
  </reference>
  <reference>
    <citation>Nucifora G, Schuijf JD, Tops LF, van Werkhoven JM, Kajander S, Jukema JW, Schreur JH, Heijenbrok MW, Trines SA, Gaemperli O, Turta O, Kaufmann PA, Knuuti J, Schalij MJ, Bax JJ. Prevalence of coronary artery disease assessed by multislice computed tomography coronary angiography in patients with paroxysmal or persistent atrial fibrillation. Circ Cardiovasc Imaging. 2009 Mar;2(2):100-6. doi: 10.1161/CIRCIMAGING.108.795328. Epub 2009 Jan 26.</citation>
    <PMID>19808575</PMID>
  </reference>
  <reference>
    <citation>Abidov A, Hachamovitch R, Rozanski A, Hayes SW, Santos MM, Sciammarella MG, Cohen I, Gerlach J, Friedman JD, Germano G, Berman DS. Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography. J Am Coll Cardiol. 2004 Sep 1;44(5):1062-70. doi: 10.1016/j.jacc.2004.05.076.</citation>
    <PMID>15337220</PMID>
  </reference>
  <reference>
    <citation>Smit MD, Tio RA, Slart RH, Zijlstra F, Van Gelder IC. Myocardial perfusion imaging does not adequately assess the risk of coronary artery disease in patients with atrial fibrillation. Europace. 2010 May;12(5):643-8. doi: 10.1093/europace/eup404. Epub 2009 Dec 17.</citation>
    <PMID>20022875</PMID>
  </reference>
  <reference>
    <citation>Nandalur KR, Dwamena BA, Choudhri AF, Nandalur MR, Carlos RC. Diagnostic performance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol. 2007 Oct 2;50(14):1343-53. doi: 10.1016/j.jacc.2007.06.030. Epub 2007 Sep 17.</citation>
    <PMID>17903634</PMID>
  </reference>
  <reference>
    <citation>Hamon M, Fau G, Nee G, Ehtisham J, Morello R, Hamon M. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010 May 19;12(1):29. doi: 10.1186/1532-429X-12-29.</citation>
    <PMID>20482819</PMID>
  </reference>
  <reference>
    <citation>Ablitt NA, Gao J, Keegan J, Stegger L, Firmin DN, Yang GZ. Predictive cardiac motion modeling and correction with partial least squares regression. IEEE Trans Med Imaging. 2004 Oct;23(10):1315-24. doi: 10.1109/TMI.2004.834622.</citation>
    <PMID>15493698</PMID>
  </reference>
  <reference>
    <citation>S. E. Litwin, J. Fluckiger, L. Chen, T. H. Kim, N. Pack, B. Matthews, C. McGann, R. Jiji, et al. Does fixed-dose regadenoson induce comparable myocarial perfusion reserve in patients of widely varying body size? A quantitative MRI study. American Heart Association, chicago, 2010.</citation>
  </reference>
  <reference>
    <citation>O. J. Booker, P. Bandettini, P. Kellman, J. Wilson, S. Leung, S. Vasu, S. Shanbhag, J. Henry, et al. Time resolved measure of coronary sinus flow following regadenoson administration. Journal of cardiovascular magnetic resonance, 13(1): O74, 2011.</citation>
  </reference>
  <reference>
    <citation>Harper R, Reeves B. Reporting of precision of estimates for diagnostic accuracy: a review. BMJ. 1999 May 15;318(7194):1322-3. doi: 10.1136/bmj.318.7194.1322. No abstract available.</citation>
    <PMID>10323817</PMID>
  </reference>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 19, 2012</study_first_posted>
  <results_first_submitted>October 11, 2017</results_first_submitted>
  <results_first_submitted_qc>October 11, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">November 7, 2017</results_first_posted>
  <last_update_submitted>November 17, 2017</last_update_submitted>
  <last_update_submitted_qc>November 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Brent Wilson</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>MRI</keyword>
  <keyword>Atrial Fibrillation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Regadenoson</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Regadenoson MRI</title>
          <description>Participants with atrial fibrillation receiving regadenoson stress MRI</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Regadenoson MRI</title>
          <description>Participants with atrial fibrillation receiving regadenoson stress MRI</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Sensitivity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</title>
        <description>Determination of sensitivity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
        <time_frame>one MRI, up to 1 hour</time_frame>
        <population>Results for 4 subjects are unevaluable due to delays in blinded reading of MRI scans and non-comparable due to personnel turnover in blinded MRI readers</population>
        <group_list>
          <group group_id="O1">
            <title>Regadenoson MRI</title>
            <description>Participants with atrial fibrillation receiving regadenoson stress MRI</description>
          </group>
        </group_list>
        <measure>
          <title>Sensitivity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</title>
          <description>Determination of sensitivity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
          <population>Results for 4 subjects are unevaluable due to delays in blinded reading of MRI scans and non-comparable due to personnel turnover in blinded MRI readers</population>
          <units>Percentage of true positive cases</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="30" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Specificity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</title>
        <description>Determination of specificity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
        <time_frame>one MRI, up to 1 hour</time_frame>
        <population>Results for 4 subjects are unevaluable due to delays in blinded reading of MRI scans and non-comparable due to personnel turnover in blinded MRI readers</population>
        <group_list>
          <group group_id="O1">
            <title>Regadenoson MRI</title>
            <description>Participants with atrial fibrillation receiving regadenoson stress MRI</description>
          </group>
        </group_list>
        <measure>
          <title>Specificity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</title>
          <description>Determination of specificity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
          <population>Results for 4 subjects are unevaluable due to delays in blinded reading of MRI scans and non-comparable due to personnel turnover in blinded MRI readers</population>
          <units>Percentage of true negative cases</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="81" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accuracy of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</title>
        <description>Determination of accuracy of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Accuracy is the percentage of correctly classified subjects (true positive + true negative) among all subjects (true positive + true negative + false positive + false negative). Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
        <time_frame>one MRI, up to 1 hour</time_frame>
        <population>Results for 4 subjects are unevaluable due to delays in blinded reading of MRI scans and non-comparable due to personnel turnover in blinded MRI readers</population>
        <group_list>
          <group group_id="O1">
            <title>Regadenoson MRI</title>
            <description>Participants with atrial fibrillation receiving regadenoson stress MRI</description>
          </group>
        </group_list>
        <measure>
          <title>Accuracy of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)</title>
          <description>Determination of accuracy of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Accuracy is the percentage of correctly classified subjects (true positive + true negative) among all subjects (true positive + true negative + false positive + false negative). Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.</description>
          <population>Results for 4 subjects are unevaluable due to delays in blinded reading of MRI scans and non-comparable due to personnel turnover in blinded MRI readers</population>
          <units>Percentage of correct total cases</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96" lower_limit="78" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Subjects monitored for safety events during the entire magnetic resonance imaging session; up to 1 hour</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Regadenoson MRI</title>
          <description>Participants with atrial fibrillation receiving regadenoson stress MRI</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Jaw Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of Breath</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chest Pressure</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Edward DiBella, Ph.D.</name_or_title>
      <organization>University of Utah, Dept. of Radiology Research</organization>
      <phone>801-585-5543</phone>
      <email>edward.dibella@hsc.utah.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01710254
org study id: REGA-12F08
nct id: NCT01710254
lead sponsor: 
has dmc: Yes
Atrial fibrillation (AF) is growing into an epidemic affecting 1 in 4 adults. There is a need
      for research to elucidate the prevalence of ischemic cardiomyopathy in patients diagnosed
      with AF. The objective of this study is to demonstrate the utility of MRI in assessment of
      coronary artery disease. The specific objective is to demonstrate sensitivity/specificity
      comparable to that reported in meta-analyses of non-AF patients and adenosine (90% /80%) in
      an AF population using the time-efficient vasodilator regadenoson that requires only a single
      intravenous (IV).
Scientific Background/Rationale:

      Atrial fibrillation (AF) is a large and growing healthcare problem worldwide. Over 7 million
      people in the U.S. and Europe currently suffer from atrial fibrillation, and this number is
      expected to double before 2050. The lifetime risk of AF is high: ~24% at age 40, and this
      risk remains fairly constant at older ages, with 22% lifetime risk at age 80 [1]. AF
      significantly increases the risk of stroke and mortality, and can greatly limit quality of
      life. Little research has been done on AF and ischemic cardiomyopathy, though it is a
      relatively common co-morbidity. CT found increased prevalence (41% vs 27%) of coronary artery
      disease (CAD) in patients with AF compared to patients with similar pre-test risk but no AF
      [2]. AF patients with a positive SPECT scan for CAD have a worse prognosis for cardiac events
      than patients with positive SPECT but without AF [3]. It was recently reported that in a
      study of 253 AF patients, that AF patients with positive SPECT studies had a very high number
      of false positives - only 15% of patients had significant CAD by angiography (compared to 67%
      in the control group) [4, 5]. Just over half of the patients were in sinus rhythm at SPECT,
      but since similar numbers of positives were seen in each half, the authors did not feel that
      imaging during AF was the cause of the poor specificity.

      Use of MRI for assessment of CAD is a growing area that entails no radiation exposure to the
      patient. Advances in MRI have made it possible to accurately detect CAD, either as well or
      better than SPECT in unselected populations [6, 7]. However, adoption of MRI myocardial
      perfusion scans has been limited in part due to the challenges associated with the use of
      adenosine. Adenosine requires starting a second IV, and to use either a special expensive
      MRI-compatible infusion pump to deliver the drug, or long lengths of tubing to run to a pump
      outside the scanner room. Neither solution is ideal, and regadenoson would not require any
      such pumps or the starting of a second IV. Here the investigators propose to determine the
      sensitivity/specificity for dynamic contrast-enhanced myocardial perfusion MRI with the
      vasodilator regadenoson in a subpopulation of patients - those with atrial fibrillation.

      The investigators have a great deal of experience with stress and rest myocardial perfusion
      MRI. In a preliminary study imaging three patients with AF that then went to X-ray
      angiography (cath), two of the three subjects had significant stenoses by cath, and one did
      not. This agreed with the regadenoson stress perfusion MRI findings. These MRI acquisitions
      were performed on a Siemens Verio MRI scanner. The Verio operates at twice the magnetic field
      strength (3 Tesla, or 3T) of most MRI scanners, which operate at 1.5T. The higher magnetic
      field offers images with significantly less noise (almost twice the signal-to-noise ratio).

      Objective: To demonstrate sensitivity/specificity comparable to that reported in
      meta-analyses of non-AF patients and adenosine (90%/80% [6, 7]), in an atrial fibrillation
      population while using the time-efficient vasodilator regadenoson that requires only a single
      IV.

      Study Design: This will be a prospective, open-label, comparative trial using MRI.
      Non-invasive MRI measurements of resting flow and flow at regadenoson stress will be obtained
      in each subject during a one hour MRI exam using our advanced MRI acquisition techniques.
      Sensitivity/specificity of regadenoson stress MRI will be determined using x-ray angiography
      as the standard. X-ray angiography will be done as standard-of-care, and is not an
      intervention of this clinical trial.

      Study Procedure: Each subject will undergo a single MRI scanning session. Caffeine will be
      stopped 12 hours prior to the procedure. One IV will be started and subjects positioned in
      the scanner. Resting perfusion with Multihance Gd-BOPTA contrast agent will be performed
      first. The perfusion acquisition acquires 3-6 short axis slices each heartbeat and lasts for
      one minute. Then a standard regadenoson injection of 400ug/5cc will be given and MR imaging
      performed with a Gd-BOPTA contrast agent bolus 60-100 seconds later [9] [10].
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Sensitivity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)
time frame: one MRI, up to 1 hour
description: Determination of sensitivity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.
measure: Specificity of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)
time frame: one MRI, up to 1 hour
description: Determination of specificity of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.
measure: Accuracy of Regadenoson Stress-MRI for Detection of Coronary Artery Disease (CAD)
time frame: one MRI, up to 1 hour
description: Determination of accuracy of Regadenoson stress-MRI in the detection of CAD, using x-ray angiography as the standard. Accuracy is the percentage of correctly classified subjects (true positive + true negative) among all subjects (true positive + true negative + false positive + false negative). Perfusion images interpreted by three blinded readers as normal or abnormal; majority results of the three blinded readers are reported.
arm group label: Regadenoson MRI
arm group type: Experimental
description: Participants with AF receiving regadenoson stress MRI, using Gadobenate dimeglumine
intervention type: Drug
intervention name: Regadenoson MRI
description: AF patients will be provided with a regadenoson stress MRI to see if coronary artery disease can be detected with more sensitivity /specificity.
arm group label: Regadenoson MRI
other name: Lexiscan
intervention type: Drug
intervention name: Gadobenate dimeglumine
description: Resting perfusion with Multihance Gd-BOPTA contrast agent will be performed first, then a regadenoson injection will be given and MR imaging performed with a Gd-BOPTA contrast agent bolus 60-100 seconds later.
arm group label: Regadenoson MRI
other name: Gd-BOPTA
other name: Multihance
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Brent Wilson, MD
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
citation: Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004 Aug 31;110(9):1042-6. doi: 10.1161/01.CIR.0000140263.20897.42. Epub 2004 Aug 16.
PMID: 15313941
citation: Nucifora G, Schuijf JD, Tops LF, van Werkhoven JM, Kajander S, Jukema JW, Schreur JH, Heijenbrok MW, Trines SA, Gaemperli O, Turta O, Kaufmann PA, Knuuti J, Schalij MJ, Bax JJ. Prevalence of coronary artery disease assessed by multislice computed tomography coronary angiography in patients with paroxysmal or persistent atrial fibrillation. Circ Cardiovasc Imaging. 2009 Mar;2(2):100-6. doi: 10.1161/CIRCIMAGING.108.795328. Epub 2009 Jan 26.
PMID: 19808575
citation: Abidov A, Hachamovitch R, Rozanski A, Hayes SW, Santos MM, Sciammarella MG, Cohen I, Gerlach J, Friedman JD, Germano G, Berman DS. Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography. J Am Coll Cardiol. 2004 Sep 1;44(5):1062-70. doi: 10.1016/j.jacc.2004.05.076.
PMID: 15337220
citation: Smit MD, Tio RA, Slart RH, Zijlstra F, Van Gelder IC. Myocardial perfusion imaging does not adequately assess the risk of coronary artery disease in patients with atrial fibrillation. Europace. 2010 May;12(5):643-8. doi: 10.1093/europace/eup404. Epub 2009 Dec 17.
PMID: 20022875
citation: Nandalur KR, Dwamena BA, Choudhri AF, Nandalur MR, Carlos RC. Diagnostic performance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol. 2007 Oct 2;50(14):1343-53. doi: 10.1016/j.jacc.2007.06.030. Epub 2007 Sep 17.
PMID: 17903634
citation: Hamon M, Fau G, Nee G, Ehtisham J, Morello R, Hamon M. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010 May 19;12(1):29. doi: 10.1186/1532-429X-12-29.
PMID: 20482819
citation: Ablitt NA, Gao J, Keegan J, Stegger L, Firmin DN, Yang GZ. Predictive cardiac motion modeling and correction with partial least squares regression. IEEE Trans Med Imaging. 2004 Oct;23(10):1315-24. doi: 10.1109/TMI.2004.834622.
PMID: 15493698
citation: S. E. Litwin, J. Fluckiger, L. Chen, T. H. Kim, N. Pack, B. Matthews, C. McGann, R. Jiji, et al. Does fixed-dose regadenoson induce comparable myocarial perfusion reserve in patients of widely varying body size? A quantitative MRI study. American Heart Association, chicago, 2010.
citation: O. J. Booker, P. Bandettini, P. Kellman, J. Wilson, S. Leung, S. Vasu, S. Shanbhag, J. Henry, et al. Time resolved measure of coronary sinus flow following regadenoson administration. Journal of cardiovascular magnetic resonance, 13(1): O74, 2011.
citation: Harper R, Reeves B. Reporting of precision of estimates for diagnostic accuracy: a review. BMJ. 1999 May 15;318(7194):1322-3. doi: 10.1136/bmj.318.7194.1322. No abstract available.
PMID: 10323817
responsible party type: Principal Investigator
investigator affiliation: University of Utah
investigator full name: Brent Wilson
investigator title: Associate Professor
mesh term: Atrial Fibrillation
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Regadenoson
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 