<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/NCT01705509</url>
  </required_header>
  <id_info>
    <org_study_id>20121250</org_study_id>
    <nct_id>NCT01705509</nct_id>
  </id_info>
  <brief_title>The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)</brief_title>
  <acronym>ERIC</acronym>
  <official_title>The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardiovascular Institute of the South Clinical Research Corporation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cardiovascular Institute of the South Clinical Research Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a proof of concept trial using ranolazine, a medication, in patients with known&#xD;
      Coronary Artery Disease and reduced left ventricular function, EF &lt; 40%. We propose that&#xD;
      ranolazine therapy will result in demonstrative improvements in cardiac function that can be&#xD;
      objectively assessed using the parameters measured with CPET. We propose that demonstrative&#xD;
      improvement in CPET parameters on ranolazine will translate into improved patient outcomes&#xD;
      for this patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Selected patients will undergo a CPET evaluation. The initial CPET will identify patients&#xD;
      with underlying ischemia and serve as a baseline study. Ischemia will be assessed using: 1)&#xD;
      peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood&#xD;
      is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units&#xD;
      of VO2; 3) the O2-pulse measurements at the AT peak VO2: estimate stroke volume at those&#xD;
      levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides&#xD;
      information on the ability of the cardiac output to increase. Patients whoseCPET results meet&#xD;
      the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week&#xD;
      +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum&#xD;
      therapy. CPET results before and after therapy will undergo a statistical comparison. The&#xD;
      initial off treatment CPET measurement will serve as the control to assess changes found&#xD;
      during therapy. No medication changes or revascularization procedures will occur during the&#xD;
      study. If patients require and undergo a medication change or a revascularization procedure,&#xD;
      they will be excluded from the study.&#xD;
&#xD;
      Patients will be contacted at the completion of week one prior to up titration, then at the&#xD;
      end of week two to ensure tolerance and compliance with the 1000mg BID dose. Patients will&#xD;
      perform the second CPET study at week four +/- 1 week. The trial medication will be assessed&#xD;
      and counted to ensure that patients have taken there allotted pill count for the duration of&#xD;
      the study. Patients who are found to be noncompliant of less than 80% will be excluded from&#xD;
      the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to lack of resources.&#xD;
  </why_stopped>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">March 31, 2017</completion_date>
  <primary_completion_date type="Actual">March 31, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiopulmonary Exercise Test Parameters (CPET).</measure>
    <time_frame>30 days</time_frame>
    <description>CPET parameters assessed will include the peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units of VO2; 3) the O2-pulse measurements at the AT and peak VO2: estimate stroke volume at those levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides information on the ability of the cardiac output to increase.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Ranolazine Treatment Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All patients who meet the criteria of ischemia will receive ranolazine after enrollment. The initial CPET will serve as the control. The second CPET after 30-days of therapy will serve as the therapy arm. CPET parameters will be assessed and compared both on and off therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranolazine</intervention_name>
    <description>The intervention will be ranolazine therapy after the initial CPET. The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison. The initial off treatment CPET measurement will serve as the control to assess changes found during therapy.</description>
    <arm_group_label>Ranolazine Treatment Arm</arm_group_label>
    <other_name>Ranexa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt; 18 years of age will be enrolled in the trial.&#xD;
&#xD;
          -  Stable patients without hospitalizations, medication changes or cardiac intervention&#xD;
             within one month of the study will be enrolled.&#xD;
&#xD;
          -  Patients must be able to complete the CPET protocol and must have demonstrable&#xD;
             ischemia on the initial CPET evaluation.&#xD;
&#xD;
          -  Patients must have a documented ejection fraction &lt; 40%&#xD;
&#xD;
             a. LV function can be assessed via: i. Echocardiogram ii. MUGA or Nuclear Perfusion&#xD;
             Scan iii. Left ventriculogram&#xD;
&#xD;
          -  Patients must be Ranexa naive and without contraindication for Ranexa therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  QTc&gt;500 msec on resting EKG&#xD;
&#xD;
          -  Hepatic Impairment (Child-Pugh class A, B or C)&#xD;
&#xD;
          -  Have received prior treatment with ranolazine&#xD;
&#xD;
          -  Treatment with QT prolonging drugs as class 1A (e.g., quinidine), class III (e.g.,&#xD;
             sotalol, dofetilide) anti-arrhythmics, amiodarone and anti-psychotics (e.g.,&#xD;
             thioridazine, ziprasidone)&#xD;
&#xD;
          -  Treatment with potent or moderately potent CYP3A inhibitors including ketoconazole and&#xD;
             other azole antifungals, diltiazem, verapamil, macrolide antibiotics, HIV protease&#xD;
             inhibitors or consumption of grapefruit juice or grapefruit juice containing products&#xD;
&#xD;
          -  Have participated in another trial of an investigational device or drug within 30 days&#xD;
             of screening&#xD;
&#xD;
          -  Have end stage renal disease requiring dialysis&#xD;
&#xD;
          -  Have any chronic illness likely to effect compliance with the protocol&#xD;
&#xD;
          -  Have second or third degree atrioventricular block in the absence of a functioning&#xD;
             ventricular pacemaker&#xD;
&#xD;
          -  Have uncontrolled clinically significant cardiac arrhythmias, or a history of&#xD;
             ventricular fibrillation, torsade de pointes, or other life-threatening ventricular&#xD;
             arrhythmias&#xD;
&#xD;
          -  Uncontrolled HTN defined as BP &gt; /= 160/100 mm Hg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Agostino G Ingraldi, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardiovascular Institute of the South</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cardiovascular Institute of the South</name>
      <address>
        <city>Lafayette</city>
        <state>Louisiana</state>
        <zip>70506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):948-54. doi: 10.1161/CIRCULATIONAHA.109.192666. No abstract available. Erratum In: Circulation. 2010 Mar 30;121(12):e259.</citation>
    <PMID>20177011</PMID>
  </reference>
  <reference>
    <citation>McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart failure: public and private health burden. Eur Heart J. 1998 Dec;19 Suppl P:P9-16.</citation>
    <PMID>9886707</PMID>
  </reference>
  <reference>
    <citation>Wenger NK, Chaitman B, Vetrovec GW. Gender comparison of efficacy and safety of ranolazine for chronic angina pectoris in four randomized clinical trials. Am J Cardiol. 2007 Jan 1;99(1):11-8. doi: 10.1016/j.amjcard.2006.07.052. Epub 2006 Nov 2.</citation>
    <PMID>17196454</PMID>
  </reference>
  <reference>
    <citation>Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006 Jul;92 Suppl 4(Suppl 4):iv6-iv14. doi: 10.1136/hrt.2005.078790.</citation>
    <PMID>16775092</PMID>
  </reference>
  <reference>
    <citation>Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. No abstract available.</citation>
    <PMID>16717165</PMID>
  </reference>
  <reference>
    <citation>Belardinelli R, Lacalaprice F, Carle F, Minnucci A, Cianci G, Perna G, D'Eusanio G. Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing. Eur Heart J. 2003 Jul;24(14):1304-13. doi: 10.1016/s0195-668x(03)00210-0.</citation>
    <PMID>12871687</PMID>
  </reference>
  <reference>
    <citation>Contini M, Andreini D, Agostoni P. Cardiopulmonary exercise test evidence of isolated right coronary artery disease. Int J Cardiol. 2006 Nov 10;113(2):281-2. doi: 10.1016/j.ijcard.2005.09.033. Epub 2005 Nov 28.</citation>
    <PMID>16316693</PMID>
  </reference>
  <reference>
    <citation>Klainman E, Fink G, Lebzelter J, Zafrir N. Assessment of functional results after percutaneous transluminal coronary angioplasty by cardiopulmonary exercise test. Cardiology. 1998 May;89(4):257-62. doi: 10.1159/000006797.</citation>
    <PMID>9643272</PMID>
  </reference>
  <reference>
    <citation>Itoh, H et al. Oxygen uptake abnormalities during exercise in coronary artery disease. In Cardiopulmonary Exercise Testing and Cardiovascular Health. Edited by K. Wasserman, Published by Futura Publishing Company, Armonk NY, 2002.</citation>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <results_first_submitted>August 29, 2019</results_first_submitted>
  <results_first_submitted_qc>February 5, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 18, 2020</results_first_posted>
  <last_update_submitted>February 5, 2020</last_update_submitted>
  <last_update_submitted_qc>February 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>The Effects of Ranolazine on CPET Parameters in Ischemic</keyword>
  <keyword>Cardiomyopathy Patients</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranolazine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 10, 2012</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT01705509/ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 24, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT01705509/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CPET Control / CPET With Ranexa</title>
          <description>The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Inclusion CPET</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screen Failure</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>CPET w/ Ranexa</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screen Failure</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CPET Control / CPET With Ranexa</title>
          <description>Enrolled patients will undergo a CPET evaluation. Beta Blockers will be held day prior to and day of CPET. The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg B ID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison. The initial off treatment CPET measurement will serve as the control to assess changes found during therapy. No medication changes or revascularization procedures will occur during the study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68" lower_limit="58" upper_limit="79"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cardiopulmonary Exercise Test Parameters (CPET).</title>
        <description>CPET parameters assessed will include the peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units of VO2; 3) the O2-pulse measurements at the AT and peak VO2: estimate stroke volume at those levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides information on the ability of the cardiac output to increase.</description>
        <time_frame>30 days</time_frame>
        <population>Number of Participants who Reached CPET Milestones</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>All patients who meet the criteria of ischemia will receive ranolazine after enrollment. The initial CPET will serve as the control. The second CPET after 30-days of therapy will serve as the therapy arm. CPET parameters will be assessed and compared both on and off therapy.&#xD;
Ranolazine: The intervention will be ranolazine therapy after the initial CPET. The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison. The initial off treatment CPET measurement will serve as the control to assess changes found during therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiopulmonary Exercise Test Parameters (CPET).</title>
          <description>CPET parameters assessed will include the peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units of VO2; 3) the O2-pulse measurements at the AT and peak VO2: estimate stroke volume at those levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides information on the ability of the cardiac output to increase.</description>
          <population>Number of Participants who Reached CPET Milestones</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Failed Initial CPET</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Withdrew Prior to CPET</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Screenfailed due to Ranolazine Intolerance</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Completed</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CPET Control / CPET With Ranexa</title>
          <description>The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy.</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="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="4" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>CAD (Ranexa 1000mg BID Treatment)</sub_title>
                <description>Coronary artery disease</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Ranexa Intolerant (Ranexa 1000mg BID Treatment)</sub_title>
                <description>Subject intolerant to Ranexa.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Headache (Ranexa 1000mg BID Treatment)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Agostino Ingraldi, MD, FACC</name_or_title>
      <organization>Cardiovascular Institute of the South</organization>
      <phone>337-988-1585</phone>
      <email>Agostino.Ingraldi@cardio.com</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/NCT01705509
org study id: 20121250
nct id: NCT01705509
lead sponsor: 
collaborator: 
has dmc: No
This is a proof of concept trial using ranolazine, a medication, in patients with known
      Coronary Artery Disease and reduced left ventricular function, EF < 40%. We propose that
      ranolazine therapy will result in demonstrative improvements in cardiac function that can be
      objectively assessed using the parameters measured with CPET. We propose that demonstrative
      improvement in CPET parameters on ranolazine will translate into improved patient outcomes
      for this patient population.
Selected patients will undergo a CPET evaluation. The initial CPET will identify patients
      with underlying ischemia and serve as a baseline study. Ischemia will be assessed using: 1)
      peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood
      is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units
      of VO2; 3) the O2-pulse measurements at the AT peak VO2: estimate stroke volume at those
      levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides
      information on the ability of the cardiac output to increase. Patients whoseCPET results meet
      the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week
      +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum
      therapy. CPET results before and after therapy will undergo a statistical comparison. The
      initial off treatment CPET measurement will serve as the control to assess changes found
      during therapy. No medication changes or revascularization procedures will occur during the
      study. If patients require and undergo a medication change or a revascularization procedure,
      they will be excluded from the study.

      Patients will be contacted at the completion of week one prior to up titration, then at the
      end of week two to ensure tolerance and compliance with the 1000mg BID dose. Patients will
      perform the second CPET study at week four +/- 1 week. The trial medication will be assessed
      and counted to ensure that patients have taken there allotted pill count for the duration of
      the study. Patients who are found to be noncompliant of less than 80% will be excluded from
      the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Cardiopulmonary Exercise Test Parameters (CPET).
time frame: 30 days
description: CPET parameters assessed will include the peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units of VO2; 3) the O2-pulse measurements at the AT and peak VO2: estimate stroke volume at those levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides information on the ability of the cardiac output to increase.
arm group label: Ranolazine Treatment Arm
arm group type: Other
description: All patients who meet the criteria of ischemia will receive ranolazine after enrollment. The initial CPET will serve as the control. The second CPET after 30-days of therapy will serve as the therapy arm. CPET parameters will be assessed and compared both on and off therapy.
intervention type: Drug
intervention name: Ranolazine
description: The intervention will be ranolazine therapy after the initial CPET. The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison. The initial off treatment CPET measurement will serve as the control to assess changes found during therapy.
arm group label: Ranolazine Treatment Arm
other name: Ranexa
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Agostino G Ingraldi, M.D.
role: Principal Investigator
affiliation: Cardiovascular Institute of the South
facility: 
country: United States
citation: Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):948-54. doi: 10.1161/CIRCULATIONAHA.109.192666. No abstract available. Erratum In: Circulation. 2010 Mar 30;121(12):e259.
PMID: 20177011
citation: McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart failure: public and private health burden. Eur Heart J. 1998 Dec;19 Suppl P:P9-16.
PMID: 9886707
citation: Wenger NK, Chaitman B, Vetrovec GW. Gender comparison of efficacy and safety of ranolazine for chronic angina pectoris in four randomized clinical trials. Am J Cardiol. 2007 Jan 1;99(1):11-8. doi: 10.1016/j.amjcard.2006.07.052. Epub 2006 Nov 2.
PMID: 17196454
citation: Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006 Jul;92 Suppl 4(Suppl 4):iv6-iv14. doi: 10.1136/hrt.2005.078790.
PMID: 16775092
citation: Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. No abstract available.
PMID: 16717165
citation: Belardinelli R, Lacalaprice F, Carle F, Minnucci A, Cianci G, Perna G, D'Eusanio G. Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing. Eur Heart J. 2003 Jul;24(14):1304-13. doi: 10.1016/s0195-668x(03)00210-0.
PMID: 12871687
citation: Contini M, Andreini D, Agostoni P. Cardiopulmonary exercise test evidence of isolated right coronary artery disease. Int J Cardiol. 2006 Nov 10;113(2):281-2. doi: 10.1016/j.ijcard.2005.09.033. Epub 2005 Nov 28.
PMID: 16316693
citation: Klainman E, Fink G, Lebzelter J, Zafrir N. Assessment of functional results after percutaneous transluminal coronary angioplasty by cardiopulmonary exercise test. Cardiology. 1998 May;89(4):257-62. doi: 10.1159/000006797.
PMID: 9643272
citation: Itoh, H et al. Oxygen uptake abnormalities during exercise in coronary artery disease. In Cardiopulmonary Exercise Testing and Cardiovascular Health. Edited by K. Wasserman, Published by Futura Publishing Company, Armonk NY, 2002.
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Ranolazine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 