<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/NCT03257683</url>
  </required_header>
  <id_info>
    <org_study_id>STH 16-012</org_study_id>
    <nct_id>NCT03257683</nct_id>
  </id_info>
  <brief_title>RANOLAZINE STUDY: Speckle Tracking Derived Myocardial Strain</brief_title>
  <official_title>RANOLAZINE STUDY: The Effect of Ranolazine on Speckle Tracking Derived Myocardial Strain in Regions of Non-Revascularizable Ischemic Myocardium</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Saint Thomas Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Saint Thomas Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to collect data to determine if the medication, Ranolazine,&#xD;
      effects heart muscle function in patients who have areas of non-revascularizable heart&#xD;
      muscle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many cardiac patients with severe coronary artery disease have areas of ischemic LV&#xD;
      myocardium that cannot be revascularized (Non-R). The investigators propose to identify such&#xD;
      patients via retrospective case review of CMRI data, as well as identify the exact regions&#xD;
      which specify Non-R coronary anatomy. This selected study group will have a specific&#xD;
      echocardiographic imaging protocol performed, which includes the known ischemic regions. All&#xD;
      segments will be collected and analyzed as a pre-therapeutic baseline using specialized STE&#xD;
      software to derive strain values. Following eight (8) weeks of ranolazine therapy, each&#xD;
      subject will be re-interrogated with the same echocardiographic imaging protocol and have&#xD;
      identical measurements of regional strain performed. Ranolazine will be added to the&#xD;
      patients' usual medical therapy. Each patient will serve as their own control, from baseline&#xD;
      to post therapeutic state.&#xD;
&#xD;
      It is the hypothesis of the investigators, that additional therapeutic dosing of ranolazine&#xD;
      will improve regional and perhaps global myocardial function. Improvement in LV mechanical&#xD;
      function (regional and global) will be quantitated and objectively elucidated by STE derived&#xD;
      myocardial strain as described further in this document.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">April 14, 2017</start_date>
  <completion_date type="Actual">February 16, 2018</completion_date>
  <primary_completion_date type="Actual">November 16, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of strain</measure>
    <time_frame>8 weeks</time_frame>
    <description>Changes in 3D regional left ventricular myocardial strain assessed by speckle-tracking</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left ventricular function</measure>
    <time_frame>8 weeks</time_frame>
    <description>2D global longitudinal strain and various other echo parameters of left ventricular function</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Severe Coronary Artery Disease</condition>
  <condition>Ischaemic Myocardial Dysfunction</condition>
  <arm_group>
    <arm_group_label>Selected group with cardiac ischemia</arm_group_label>
    <description>This selected study group will have a specific echocardiographic imaging protocol performed, which includes the known ischemic regions. All segments will be collected and analyzed as a pre-therapeutic baseline using specialized STE software to derive strain values. Following eight (8) weeks of ranolazine therapy, each subject will be re-interrogated with the same echocardiographic imaging protocol and have identical measurements of regional strain performed. Ranolazine will be added to the patients' usual medical therapy. Each patient will serve as their own control, from baseline to post therapeutic state.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranolazine</intervention_name>
    <description>Study group will receive additional therapeutic dosing of drug.</description>
    <arm_group_label>Selected group with cardiac ischemia</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Study population will be either male or female, age 18 or greater with stable GDMT for 60&#xD;
        days prior to enrollment. They will be in normal sinus rhythm with coronary artery&#xD;
        revascularization more than 60 days prior to enrollment, with a non-revascularizable area&#xD;
        of myocardial ischemia as determined by stress MRI. They will be able to perform the&#xD;
        bicycle stress echocardiogram and able to provide written informed consent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt; 18 Stable GDMT for 60 days prior to enrollment Normal sinus rhythm Coronary&#xD;
             artery revascularization &gt; 60 days prior to enrollment Non-revascularizable area of&#xD;
             myocardial ischemia as determined by stress MRI Able to perform the bicycle stress&#xD;
             echocardiograms Able to provide written, informed consent Women of childbearing&#xD;
             potential with negative pregnancy test at the index visit, and consent to use&#xD;
             effective contraception throughout the study period and up to at least 14 days&#xD;
             following the last dose of study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  More than 1+MR, aortic stenosis, aortic insufficiency, mitral stenosis Serious&#xD;
             co-morbidities with predicted life expectancy &lt;1 year Patients not in normal sinus&#xD;
             rhythm (NSR) Patients who have undergone coronary artery revascularization (PCI, CABG)&#xD;
             within 60 days Pregnant or unknown pregnancy status Liver cirrhosis Patients&#xD;
             unwilling/unable to provide written, informed consent Concomitant use of QTc&#xD;
             prolonging drugs, potassium channel variants resulting in a long QT interval, patients&#xD;
             with a family history of (or congenital) long QT syndrome, and patients with known&#xD;
             acquired QT interval prolongation Concomitant use of strong CYP3A inhibitors including&#xD;
             ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir,&#xD;
             indinavir, and saquinavir Concomitant use of CYP3A4 inducers such as rifampin,&#xD;
             rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort&#xD;
             Breast feeding Atrial fibrillation or frequent atrial or ventricular ectopy Moderate&#xD;
             CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin) P-gp inhibitors (e.g.,&#xD;
             cyclosporine) which increase ranolazine exposure Renal failure. Patients with&#xD;
             Creatinine clearance less than 30ml/min . Safety Considerations for patients with the&#xD;
             following drugs/conditions CYP3A substrates: Limit simvastatin to 20 mg when used with&#xD;
             ranolazine. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A&#xD;
             substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus)&#xD;
             may need to be reduced with ranolazine OCT2 substrates: Limit the dose of metformin to&#xD;
             1700 mg daily when used with ranolazine 1000 mg twice daily. Doses of other OCT2&#xD;
             substrates may require adjusted doses Drugs transported by P-gp (e.g., digoxin), or&#xD;
             drugs metabolized by CYP2D6 (e.g., tricyclic antidepressants) may need reduced doses&#xD;
             when used with ranolazine Renal failure: Patients with creatinine clearance less than&#xD;
             30ml/min are excluded from participation in this study. Monitor renal function after&#xD;
             initiation and periodically in patients with moderate to severe renal impairment (CrCL&#xD;
             &lt; 60 mL/min). If acute renal failure develops, discontinue ranolazine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Douglas J Pearce, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Saint Thomas Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Saint Thomas Heart at Saint Thomas West</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>April 6, 2018</last_update_submitted>
  <last_update_submitted_qc>April 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranolazine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03257683
org study id: STH 16-012
nct id: NCT03257683
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to collect data to determine if the medication, Ranolazine,
      effects heart muscle function in patients who have areas of non-revascularizable heart
      muscle.
Many cardiac patients with severe coronary artery disease have areas of ischemic LV
      myocardium that cannot be revascularized (Non-R). The investigators propose to identify such
      patients via retrospective case review of CMRI data, as well as identify the exact regions
      which specify Non-R coronary anatomy. This selected study group will have a specific
      echocardiographic imaging protocol performed, which includes the known ischemic regions. All
      segments will be collected and analyzed as a pre-therapeutic baseline using specialized STE
      software to derive strain values. Following eight (8) weeks of ranolazine therapy, each
      subject will be re-interrogated with the same echocardiographic imaging protocol and have
      identical measurements of regional strain performed. Ranolazine will be added to the
      patients' usual medical therapy. Each patient will serve as their own control, from baseline
      to post therapeutic state.

      It is the hypothesis of the investigators, that additional therapeutic dosing of ranolazine
      will improve regional and perhaps global myocardial function. Improvement in LV mechanical
      function (regional and global) will be quantitated and objectively elucidated by STE derived
      myocardial strain as described further in this document.
observational model: Case-Only
time perspective: Prospective
measure: Measurement of strain
time frame: 8 weeks
description: Changes in 3D regional left ventricular myocardial strain assessed by speckle-tracking
measure: Left ventricular function
time frame: 8 weeks
description: 2D global longitudinal strain and various other echo parameters of left ventricular function
arm group label: Selected group with cardiac ischemia
description: This selected study group will have a specific echocardiographic imaging protocol performed, which includes the known ischemic regions. All segments will be collected and analyzed as a pre-therapeutic baseline using specialized STE software to derive strain values. Following eight (8) weeks of ranolazine therapy, each subject will be re-interrogated with the same echocardiographic imaging protocol and have identical measurements of regional strain performed. Ranolazine will be added to the patients' usual medical therapy. Each patient will serve as their own control, from baseline to post therapeutic state.
intervention type: Drug
intervention name: Ranolazine
description: Study group will receive additional therapeutic dosing of drug.
arm group label: Selected group with cardiac ischemia
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Douglas J Pearce, MD
role: Principal Investigator
affiliation: Saint Thomas Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Ranolazine
sharing ipd: No