<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/NCT01685840</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00033097</org_study_id>
    <nct_id>NCT01685840</nct_id>
  </id_info>
  <brief_title>Guiding Evidence Based Therapy Using Biomarker Intensified Treatment</brief_title>
  <acronym>GUIDE-IT</acronym>
  <official_title>Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective is to determine the efficacy of a strategy of biomarker-guided therapy&#xD;
      compared with usual care in high risk patients with left ventricular systolic dysfunction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Heart failure is a common disorder in which the heart cannot pump enough blood to meet the&#xD;
      needs of the rest of the body. Common symptoms of heart failure include shortness of breath,&#xD;
      swelling, and fatigue. Standard treatment for heart failure include diuretics to control&#xD;
      fluid, as well as drugs called &quot;neurohormonal antagonists&quot; (such as beta-blockers and&#xD;
      ACE-inhibitors) that help the heart work more efficiently and prevent worsening of heart&#xD;
      function. Typically, doctors adjust these medicines based on their clinical judgment about&#xD;
      what doses and combination will work best for you. We are testing whether the use of a blood&#xD;
      test called NT-proBNP (which measures a hormone released by the heart) can help doctors do a&#xD;
      better job of adjusting these heart failure medicines over time than clinical judgment alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Project was stopped due to futility&#xD;
  </why_stopped>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">September 20, 2016</completion_date>
  <primary_completion_date type="Actual">September 20, 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>CV Death or Heart Failure Hospitalization</measure>
    <time_frame>24 Months</time_frame>
    <description>Composite of First Heart Failure Hospitalization or Cardiovascular Mortality</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause Mortality</measure>
    <time_frame>24 months</time_frame>
    <description>All-cause mortality by treatment arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Morbidity</measure>
    <time_frame>24 months</time_frame>
    <description>Days alive and not hospitalized for CV reasons</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CV Death</measure>
    <time_frame>24 months</time_frame>
    <description>CV death by treatment arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Hospitalizations for First Heart Failure</measure>
    <time_frame>24 months</time_frame>
    <description>First Heart Failure Hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Hospitalizations for Recurrent Heart Failure</measure>
    <time_frame>24 months</time_frame>
    <description>Recurrent Heart Failure Hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Moderate to Severe Depression</measure>
    <time_frame>Baseline, 3,6, 12 and 24 months</time_frame>
    <description>Percentage of patients with moderate to severe depression as measured by the Center for Epidemiologic Studies Depression Scale (CES-D).&#xD;
CES-D is a 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression. Moderate to severe depression is indicated by a score of 11 or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duke Activity Status Index (DASI)</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EQ-5D Health Index</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>The EQ-5D measures the subjects health status in 5 categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and totals them into 1 score, from -0.59 (worst) to 1 (best).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EQ-5D Visual Analog Scale</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>The EQ-5D VAS records participants self-rated health status on a vertical (0-100) scale with higher scores indicating higher Health-Related Quality of Life, where 0 = worst imaginable health state and 100 = best imaginable health state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score</measure>
    <time_frame>Baseline, 3, 6,12 and 24 months</time_frame>
    <description>This KCCQ overall score represents the mean of the following 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form-36 (SF-36) General Health Subscale</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form-36 (SF-36) Mental Health Subscale</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form-36 (SF-36) Social Functioning Subscale</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form-36 (SF-36) Physiological Functioning Subscale</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form-36 (SF-36) Vitality Subscale</measure>
    <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
    <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resource Utilization</measure>
    <time_frame>24 months</time_frame>
    <description>Observed Resource Use</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resource Utilization Cost</measure>
    <time_frame>24 months</time_frame>
    <description>Observed Hospital-Based Cost.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">894</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Usual Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Biomarker-Guided Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Usual Care</intervention_name>
    <description>Usual Care</description>
    <arm_group_label>Usual Care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Biomarker-guided care NT-proBNP</intervention_name>
    <description>Device: NT-proBNP</description>
    <arm_group_label>Biomarker-Guided Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Most recent LVEF to be ≤ 40% by any method within 12 months of randomization.&#xD;
&#xD;
          -  High risk heart failure as defined by the following criteria:&#xD;
&#xD;
        A Heart Failure Event in the prior 12 months, defined as any one of the following:&#xD;
&#xD;
          -  HF Hospitalization&#xD;
&#xD;
          -  Treatment in the Emergency Department (or equivalent) for Heart Failure&#xD;
&#xD;
          -  Outpatient treatment for heart failure with intravenous diuretics&#xD;
&#xD;
        AND&#xD;
&#xD;
          -  NT-proBNP greater than 2000 pg/mL or BNP greater than 400 pg/mL at any time during the&#xD;
             30 days prior to randomization&#xD;
&#xD;
          -  Willing to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute coronary syndrome (clinical diagnosis) or cardiac revascularization procedure&#xD;
             within 30 days&#xD;
&#xD;
          -  Cardiac resynchronization therapy (CRT) within prior 3 months or current plan to&#xD;
             implant CRT device&#xD;
&#xD;
          -  Active myocarditis, Hypertrophic obstructive cardiomyopathy, pericarditis, or&#xD;
             restrictive cardiomyopathy&#xD;
&#xD;
          -  Severe stenotic valvular disease&#xD;
&#xD;
          -  Anticipated heart transplantation or ventricular assist device within 12 months&#xD;
&#xD;
          -  Chronic inotropic therapy&#xD;
&#xD;
          -  Complex congenital heart disease&#xD;
&#xD;
          -  End stage renal disease with renal replacement therapy&#xD;
&#xD;
          -  Non cardiac terminal illness with expected survival less than 12 months&#xD;
&#xD;
          -  Women who are pregnant or planning to become pregnant&#xD;
&#xD;
          -  Inability to comply with planned study procedures&#xD;
&#xD;
          -  Enrollment or planned enrollment in another clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Felker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Heart Center PC</name>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <zip>35801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Memorial Hospital</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95819</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego Medical Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Medical Group</name>
      <address>
        <city>Coral Springs</city>
        <state>Florida</state>
        <zip>33065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Cardiology Associates, LLC</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Valley Clinical Research Center, LLC</name>
      <address>
        <city>Aurora</city>
        <state>Illinois</state>
        <zip>60504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krannert Institute of Cardiology</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metropolitan Cardiovascular Consultants</name>
      <address>
        <city>Beltsville</city>
        <state>Maryland</state>
        <zip>20705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pentucket Medical Associates</name>
      <address>
        <city>Haverhill</city>
        <state>Massachusetts</state>
        <zip>01830</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>San Luis</city>
        <state>Missouri</state>
        <zip>63112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Associates of the Delaware Valley</name>
      <address>
        <city>Cherry Hill</city>
        <state>New Jersey</state>
        <zip>08034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert Wood Johnson University Hospital</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Associates of the Delaware Valley</name>
      <address>
        <city>Sewell</city>
        <state>New Jersey</state>
        <zip>08080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronx-Lebanon Hospital Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jacobi Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein University Hospital</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Methodist Hospital</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saratoga Cardiology Associates</name>
      <address>
        <city>Saratoga Springs</city>
        <state>New York</state>
        <zip>12866</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Heart and Vascular Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LeBauer Cardiovascular Research Foundation</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capitol Area Research, LLC</name>
      <address>
        <city>Camp Hill</city>
        <state>Pennsylvania</state>
        <zip>17011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Drexel University College of Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny-Singer Research Institute</name>
      <address>
        <city>Pittsburg</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AnMed Health Medical Center</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Associates, Ltd.</name>
      <address>
        <city>Chesapeake</city>
        <state>Virginia</state>
        <zip>23320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver General Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 1Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8L 2X2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Michaels Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <results_first_submitted>September 20, 2017</results_first_submitted>
  <results_first_submitted_qc>November 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 12, 2017</results_first_posted>
  <last_update_submitted>November 10, 2017</last_update_submitted>
  <last_update_submitted_qc>November 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>894 participants were randomized</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Usual Care</title>
          <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
        </group>
        <group group_id="P2">
          <title>Biomarker-Guided Care</title>
          <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="448"/>
                <participants group_id="P2" count="446"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="119"/>
                <participants group_id="P2" count="114"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="329"/>
                <participants group_id="P2" count="332"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
                <participants group_id="P2" count="66"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Futility</title>
              <participants_list>
                <participants group_id="P1" count="197"/>
                <participants group_id="P2" count="200"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Had VAD, Dialysis or Transplant</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Usual Care</title>
          <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
        </group>
        <group group_id="B2">
          <title>Biomarker-Guided Care</title>
          <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="448"/>
            <count group_id="B2" value="446"/>
            <count group_id="B3" value="894"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="62.5" spread="13.4"/>
                    <measurement group_id="B2" value="60.4" spread="14.3"/>
                    <measurement group_id="B3" value="61.5" spread="13.9"/>
                  </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="147"/>
                    <measurement group_id="B2" value="139"/>
                    <measurement group_id="B3" value="286"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="301"/>
                    <measurement group_id="B2" value="307"/>
                    <measurement group_id="B3" value="608"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="420"/>
                    <measurement group_id="B2" value="416"/>
                    <measurement group_id="B3" value="836"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="155"/>
                    <measurement group_id="B2" value="167"/>
                    <measurement group_id="B3" value="322"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="257"/>
                    <measurement group_id="B2" value="228"/>
                    <measurement group_id="B3" value="485"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>CV Death or Heart Failure Hospitalization</title>
        <description>Composite of First Heart Failure Hospitalization or Cardiovascular Mortality</description>
        <time_frame>24 Months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>CV Death or Heart Failure Hospitalization</title>
          <description>Composite of First Heart Failure Hospitalization or Cardiovascular Mortality</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="448"/>
                <count group_id="O2" value="446"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="164"/>
                    <measurement group_id="O2" value="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.88</p_value>
            <p_value_desc>A sample size of 1100 patients was expected to provide approximately 90% power to detect a difference in the primary endpoint with an assumed type I error rate of 0.05, 2-sided. Analysis was adjusted for age, sex, ejection fraction, NT-proBNP and DM.</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.79</ci_lower_limit>
            <ci_upper_limit>1.22</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>All-cause Mortality</title>
        <description>All-cause mortality by treatment arm</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>All-cause Mortality</title>
          <description>All-cause mortality by treatment arm</description>
          <units>deaths</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="448"/>
                <count group_id="O2" value="446"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77"/>
                    <measurement group_id="O2" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.37</p_value>
            <method>Regression, Cox</method>
            <param_type>Cox Proportional Hazard</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>1.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Morbidity</title>
        <description>Days alive and not hospitalized for CV reasons</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Morbidity</title>
          <description>Days alive and not hospitalized for CV reasons</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="448"/>
                <count group_id="O2" value="446"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="616" lower_limit="595" upper_limit="637"/>
                    <measurement group_id="O2" value="626" lower_limit="605" upper_limit="646"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.53</p_value>
            <method>Bang-Tsiatis Partitioned Estimator</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20</ci_lower_limit>
            <ci_upper_limit>39</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CV Death</title>
        <description>CV death by treatment arm</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>CV Death</title>
          <description>CV death by treatment arm</description>
          <units>deaths</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="448"/>
                <count group_id="O2" value="446"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57"/>
                    <measurement group_id="O2" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.75</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.94</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.65</ci_lower_limit>
            <ci_upper_limit>1.37</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Hospitalizations for First Heart Failure</title>
        <description>First Heart Failure Hospitalization</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Hospitalizations for First Heart Failure</title>
          <description>First Heart Failure Hospitalization</description>
          <units>hospitalizations</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="448"/>
                <count group_id="O2" value="446"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="141"/>
                    <measurement group_id="O2" value="147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.76</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.04</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.82</ci_lower_limit>
            <ci_upper_limit>1.31</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Hospitalizations for Recurrent Heart Failure</title>
        <description>Recurrent Heart Failure Hospitalization</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Hospitalizations for Recurrent Heart Failure</title>
          <description>Recurrent Heart Failure Hospitalization</description>
          <units>hospitalizations</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="448"/>
                <count group_id="O2" value="446"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="277"/>
                    <measurement group_id="O2" value="350"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.08</p_value>
            <method>Anderson-Gill Intensity Model</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.29</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.97</ci_lower_limit>
            <ci_upper_limit>1.72</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Moderate to Severe Depression</title>
        <description>Percentage of patients with moderate to severe depression as measured by the Center for Epidemiologic Studies Depression Scale (CES-D).&#xD;
CES-D is a 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression. Moderate to severe depression is indicated by a score of 11 or higher.</description>
        <time_frame>Baseline, 3,6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Moderate to Severe Depression</title>
          <description>Percentage of patients with moderate to severe depression as measured by the Center for Epidemiologic Studies Depression Scale (CES-D).&#xD;
CES-D is a 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression. Moderate to severe depression is indicated by a score of 11 or higher.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="439"/>
                <count group_id="O2" value="437"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="439"/>
                    <count group_id="O2" value="437"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.6"/>
                    <measurement group_id="O2" value="36.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="355"/>
                    <count group_id="O2" value="345"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.2"/>
                    <measurement group_id="O2" value="27.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="293"/>
                    <count group_id="O2" value="301"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.6"/>
                    <measurement group_id="O2" value="27.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="236"/>
                    <count group_id="O2" value="254"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.9"/>
                    <measurement group_id="O2" value="27.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="122"/>
                    <count group_id="O2" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.4"/>
                    <measurement group_id="O2" value="25.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.636</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.628</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.586</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.669</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.949</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duke Activity Status Index (DASI)</title>
        <description>The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity).</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Duke Activity Status Index (DASI)</title>
          <description>The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity).</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="443"/>
                <count group_id="O2" value="435"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="443"/>
                    <count group_id="O2" value="435"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" spread="12.6"/>
                    <measurement group_id="O2" value="12.6" spread="13.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="357"/>
                    <count group_id="O2" value="349"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.9" spread="14.2"/>
                    <measurement group_id="O2" value="17.7" spread="14.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="298"/>
                    <count group_id="O2" value="301"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.9" spread="15.8"/>
                    <measurement group_id="O2" value="19.7" spread="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="243"/>
                    <count group_id="O2" value="260"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.4" spread="16.1"/>
                    <measurement group_id="O2" value="19.3" spread="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="126"/>
                    <count group_id="O2" value="132"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6" spread="17.8"/>
                    <measurement group_id="O2" value="18.2" spread="17.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.404</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.880</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.188</ci_lower_limit>
            <ci_upper_limit>2.947</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.219</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.478</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.881</ci_lower_limit>
            <ci_upper_limit>3.836</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.104</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.099</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.433</ci_lower_limit>
            <ci_upper_limit>4.630</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.228</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.999</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.253</ci_lower_limit>
            <ci_upper_limit>5.250</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EQ-5D Health Index</title>
        <description>The EQ-5D measures the subjects health status in 5 categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and totals them into 1 score, from -0.59 (worst) to 1 (best).</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>EQ-5D Health Index</title>
          <description>The EQ-5D measures the subjects health status in 5 categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and totals them into 1 score, from -0.59 (worst) to 1 (best).</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="439"/>
                <count group_id="O2" value="431"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="439"/>
                    <count group_id="O2" value="431"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="0.3"/>
                    <measurement group_id="O2" value="0.7" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="372"/>
                    <count group_id="O2" value="358"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="0.3"/>
                    <measurement group_id="O2" value="0.7" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="319"/>
                    <count group_id="O2" value="321"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="0.3"/>
                    <measurement group_id="O2" value="0.7" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="261"/>
                    <count group_id="O2" value="269"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="0.3"/>
                    <measurement group_id="O2" value="0.7" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="131"/>
                    <count group_id="O2" value="137"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="0.3"/>
                    <measurement group_id="O2" value="0.7" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.421</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.017</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.025</ci_lower_limit>
            <ci_upper_limit>0.060</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.239</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.028</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.018</ci_lower_limit>
            <ci_upper_limit>0.074</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.402</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.021</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.028</ci_lower_limit>
            <ci_upper_limit>0.070</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.780</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.009</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.057</ci_lower_limit>
            <ci_upper_limit>0.076</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EQ-5D Visual Analog Scale</title>
        <description>The EQ-5D VAS records participants self-rated health status on a vertical (0-100) scale with higher scores indicating higher Health-Related Quality of Life, where 0 = worst imaginable health state and 100 = best imaginable health state.</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>EQ-5D Visual Analog Scale</title>
          <description>The EQ-5D VAS records participants self-rated health status on a vertical (0-100) scale with higher scores indicating higher Health-Related Quality of Life, where 0 = worst imaginable health state and 100 = best imaginable health state.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="446"/>
                <count group_id="O2" value="445"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.2" spread="37.6"/>
                    <measurement group_id="O2" value="59.2" spread="22.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.3" spread="25.9"/>
                    <measurement group_id="O2" value="60.2" spread="27.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.5" spread="26.5"/>
                    <measurement group_id="O2" value="61.5" spread="25.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.7" spread="25.8"/>
                    <measurement group_id="O2" value="62.1" spread="24.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.9" spread="24.0"/>
                    <measurement group_id="O2" value="60.8" spread="24.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.268</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.131</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.902</ci_lower_limit>
            <ci_upper_limit>1.640</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.599</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.069</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.921</ci_lower_limit>
            <ci_upper_limit>5.058</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.852</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.389</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.486</ci_lower_limit>
            <ci_upper_limit>3.707</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.221</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-3.343</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.708</ci_lower_limit>
            <ci_upper_limit>2.022</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score</title>
        <description>This KCCQ overall score represents the mean of the following 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.</description>
        <time_frame>Baseline, 3, 6,12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score</title>
          <description>This KCCQ overall score represents the mean of the following 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="444"/>
                <count group_id="O2" value="441"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="444"/>
                    <count group_id="O2" value="441"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.7" spread="22.4"/>
                    <measurement group_id="O2" value="57.5" spread="21.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="384"/>
                    <count group_id="O2" value="373"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.2" spread="22.8"/>
                    <measurement group_id="O2" value="68.8" spread="22.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="327"/>
                    <count group_id="O2" value="332"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.1" spread="22.2"/>
                    <measurement group_id="O2" value="70.4" spread="21.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="270"/>
                    <count group_id="O2" value="279"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.3" spread="21.9"/>
                    <measurement group_id="O2" value="68.4" spread="24.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="135"/>
                    <count group_id="O2" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.6" spread="24.4"/>
                    <measurement group_id="O2" value="70.2" spread="22.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.615</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.816</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.999</ci_lower_limit>
            <ci_upper_limit>2.367</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.878</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.252</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.977</ci_lower_limit>
            <ci_upper_limit>3.482</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.441</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.406</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.989</ci_lower_limit>
            <ci_upper_limit>2.178</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.653</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.091</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.673</ci_lower_limit>
            <ci_upper_limit>5.856</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short Form-36 (SF-36) General Health Subscale</title>
        <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Short Form-36 (SF-36) General Health Subscale</title>
          <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="441"/>
                <count group_id="O2" value="436"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="441"/>
                    <count group_id="O2" value="436"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.4" spread="11.1"/>
                    <measurement group_id="O2" value="48.6" spread="10.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="348"/>
                    <count group_id="O2" value="336"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.1" spread="12.6"/>
                    <measurement group_id="O2" value="50.0" spread="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="287"/>
                    <count group_id="O2" value="294"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.5" spread="12.7"/>
                    <measurement group_id="O2" value="49.9" spread="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="238"/>
                    <count group_id="O2" value="250"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.0" spread="12.2"/>
                    <measurement group_id="O2" value="50.8" spread="12.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="121"/>
                    <count group_id="O2" value="129"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.8" spread="12.8"/>
                    <measurement group_id="O2" value="50.4" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.199</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.226</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.097</ci_lower_limit>
            <ci_upper_limit>0.645</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.465</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.742</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.735</ci_lower_limit>
            <ci_upper_limit>1.250</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.943</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.074</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.119</ci_lower_limit>
            <ci_upper_limit>1.970</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.294</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.478</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.286</ci_lower_limit>
            <ci_upper_limit>4.241</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short Form-36 (SF-36) Mental Health Subscale</title>
        <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Short Form-36 (SF-36) Mental Health Subscale</title>
          <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="441"/>
                <count group_id="O2" value="438"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="441"/>
                    <count group_id="O2" value="438"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.7" spread="20.4"/>
                    <measurement group_id="O2" value="69.8" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="352"/>
                    <count group_id="O2" value="339"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.6" spread="19.9"/>
                    <measurement group_id="O2" value="76.1" spread="21.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="291"/>
                    <count group_id="O2" value="298"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.7" spread="20.5"/>
                    <measurement group_id="O2" value="77.1" spread="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="233"/>
                    <count group_id="O2" value="250"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.5" spread="20.3"/>
                    <measurement group_id="O2" value="76.2" spread="22.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="122"/>
                    <count group_id="O2" value="129"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.6" spread="17.6"/>
                    <measurement group_id="O2" value="76.6" spread="22.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.294</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.579</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.527</ci_lower_limit>
            <ci_upper_limit>1.369</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.555</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.946</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.096</ci_lower_limit>
            <ci_upper_limit>2.203</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.643</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.798</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.178</ci_lower_limit>
            <ci_upper_limit>2.583</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.757</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.647</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.767</ci_lower_limit>
            <ci_upper_limit>3.472</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short Form-36 (SF-36) Social Functioning Subscale</title>
        <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Short Form-36 (SF-36) Social Functioning Subscale</title>
          <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="440"/>
                <count group_id="O2" value="437"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.2" spread="32.7"/>
                    <measurement group_id="O2" value="64.8" spread="30.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.4" spread="30.8"/>
                    <measurement group_id="O2" value="74.9" spread="31.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.0" spread="32.3"/>
                    <measurement group_id="O2" value="75.0" spread="32.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.4" spread="30.9"/>
                    <measurement group_id="O2" value="74.5" spread="31.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.7" spread="30.3"/>
                    <measurement group_id="O2" value="77.2" spread="31.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.837</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.484</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.102</ci_lower_limit>
            <ci_upper_limit>4.133</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.288</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.693</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.662</ci_lower_limit>
            <ci_upper_limit>2.276</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.567</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.539</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.810</ci_lower_limit>
            <ci_upper_limit>3.732</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.475</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.512</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.394</ci_lower_limit>
            <ci_upper_limit>9.419</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short Form-36 (SF-36) Physiological Functioning Subscale</title>
        <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Short Form-36 (SF-36) Physiological Functioning Subscale</title>
          <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="442"/>
                <count group_id="O2" value="433"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="442"/>
                    <count group_id="O2" value="433"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.6" spread="32.1"/>
                    <measurement group_id="O2" value="31.5" spread="31.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="355"/>
                    <count group_id="O2" value="343"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.5" spread="35.9"/>
                    <measurement group_id="O2" value="43.3" spread="37.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="294"/>
                    <count group_id="O2" value="302"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.4" spread="37.4"/>
                    <measurement group_id="O2" value="45.6" spread="37.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="238"/>
                    <count group_id="O2" value="253"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.9" spread="38.2"/>
                    <measurement group_id="O2" value="47.4" spread="37.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="129"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" spread="38.1"/>
                    <measurement group_id="O2" value="43.2" spread="38.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.696</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.057</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.250</ci_lower_limit>
            <ci_upper_limit>6.364</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.497</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.966</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.715</ci_lower_limit>
            <ci_upper_limit>7.647</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.035</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>6.564</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.456</ci_lower_limit>
            <ci_upper_limit>12.673</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.488</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.857</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.247</ci_lower_limit>
            <ci_upper_limit>10.961</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short Form-36 (SF-36) Vitality Subscale</title>
        <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
        <time_frame>Baseline, 3, 6, 12 and 24 months</time_frame>
        <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
          <group group_id="O2">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
        </group_list>
        <measure>
          <title>Short Form-36 (SF-36) Vitality Subscale</title>
          <description>SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.</description>
          <population>&quot;Number of participants analyzed&quot; is the number of participants who completed the questionnaire</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="441"/>
                <count group_id="O2" value="438"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="441"/>
                    <count group_id="O2" value="438"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.9" spread="22.5"/>
                    <measurement group_id="O2" value="44.3" spread="22.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="353"/>
                    <count group_id="O2" value="339"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.5" spread="23.6"/>
                    <measurement group_id="O2" value="54.6" spread="23.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="291"/>
                    <count group_id="O2" value="296"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.1" spread="24.6"/>
                    <measurement group_id="O2" value="55.8" spread="23.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="234"/>
                    <count group_id="O2" value="250"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.4" spread="23.6"/>
                    <measurement group_id="O2" value="55.2" spread="24.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="129"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.9" spread="24.8"/>
                    <measurement group_id="O2" value="55.9" spread="24.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.992</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.017</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.383</ci_lower_limit>
            <ci_upper_limit>3.417</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.882</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.280</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.409</ci_lower_limit>
            <ci_upper_limit>3.969</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>12 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.647</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.904</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.973</ci_lower_limit>
            <ci_upper_limit>4.782</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>24 month</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.903</p_value>
            <p_value_desc>Adjusted P-value</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.322</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.894</ci_lower_limit>
            <ci_upper_limit>5.538</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Resource Utilization</title>
        <description>Observed Resource Use</description>
        <time_frame>24 months</time_frame>
        <population>US Patients in Economics Substudy</population>
        <group_list>
          <group group_id="O1">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
        </group_list>
        <measure>
          <title>Resource Utilization</title>
          <description>Observed Resource Use</description>
          <population>US Patients in Economics Substudy</population>
          <units>events</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="373"/>
                <count group_id="O2" value="362"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of Hospitalizations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.93" spread="2.80"/>
                    <measurement group_id="O2" value="1.83" spread="2.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of ER only events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.57" spread="1.28"/>
                    <measurement group_id="O2" value="0.56" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Rehab facilities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.35"/>
                    <measurement group_id="O2" value="0.06" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total admissions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.56" spread="3.64"/>
                    <measurement group_id="O2" value="2.45" spread="3.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Hospitalizations</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.74</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>ER only events</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.45</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rehab facilities</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.67</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Total admissions</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.47</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Resource Utilization Cost</title>
        <description>Observed Hospital-Based Cost.</description>
        <time_frame>24 months</time_frame>
        <population>US Patients with billing data</population>
        <group_list>
          <group group_id="O1">
            <title>Biomarker-Guided Care</title>
            <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
          </group>
        </group_list>
        <measure>
          <title>Resource Utilization Cost</title>
          <description>Observed Hospital-Based Cost.</description>
          <population>US Patients with billing data</population>
          <units>2016 US dollars</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="363"/>
                <count group_id="O2" value="350"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hospital Costs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47,055" spread="92,270"/>
                    <measurement group_id="O2" value="34,396" spread="60,842"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physician Fees</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2,291" spread="4,128"/>
                    <measurement group_id="O2" value="1,761" spread="2,601"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Cost</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49,346" spread="96,082"/>
                    <measurement group_id="O2" value="36,157" spread="63,110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Hospital Costs</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.88</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Physician Fees</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.69</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Total Cost</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.88</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Randomization through completion of the final study visit at 24 months</time_frame>
      <desc>SAEs and AEs of Interest that occur from randomization through completion of the final study visit will be reported.</desc>
      <group_list>
        <group group_id="E1">
          <title>Usual Care</title>
          <description>Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.&#xD;
Usual Care: Usual Care</description>
        </group>
        <group group_id="E2">
          <title>Biomarker-Guided Care</title>
          <description>Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.&#xD;
Biomarker-guided care NT-proBNP: Device: NT-proBNP</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>Protocol defined</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="77" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="66" subjects_at_risk="446"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="51" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Symptomatic Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="446"/>
              </event>
              <event>
                <sub_title>Symptomatic Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Other Adverse Events</sub_title>
                <description>Other Adverse Events</description>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening renal function</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>Protocol defined</default_vocab>
        <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="157" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="178" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Symptomatic Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="446"/>
              </event>
              <event>
                <sub_title>Symptomatic Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Other Adverse Events</sub_title>
                <description>Other Adverse Events</description>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="446"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening renal function</sub_title>
                <counts group_id="E1" subjects_affected="83" subjects_at_risk="448"/>
                <counts group_id="E2" subjects_affected="91" subjects_at_risk="446"/>
              </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>G. Michael Felker, M.D.</name_or_title>
      <organization>Duke University Health System</organization>
      <phone>919-668-8919</phone>
      <email>michael.felker@duke.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/NCT01685840
org study id: Pro00033097
nct id: NCT01685840
lead sponsor: 
collaborator: 
has dmc: Yes
The primary objective is to determine the efficacy of a strategy of biomarker-guided therapy
      compared with usual care in high risk patients with left ventricular systolic dysfunction.
Heart failure is a common disorder in which the heart cannot pump enough blood to meet the
      needs of the rest of the body. Common symptoms of heart failure include shortness of breath,
      swelling, and fatigue. Standard treatment for heart failure include diuretics to control
      fluid, as well as drugs called "neurohormonal antagonists" (such as beta-blockers and
      ACE-inhibitors) that help the heart work more efficiently and prevent worsening of heart
      function. Typically, doctors adjust these medicines based on their clinical judgment about
      what doses and combination will work best for you. We are testing whether the use of a blood
      test called NT-proBNP (which measures a hormone released by the heart) can help doctors do a
      better job of adjusting these heart failure medicines over time than clinical judgment alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: CV Death or Heart Failure Hospitalization
time frame: 24 Months
description: Composite of First Heart Failure Hospitalization or Cardiovascular Mortality
measure: All-cause Mortality
time frame: 24 months
description: All-cause mortality by treatment arm
measure: Cumulative Morbidity
time frame: 24 months
description: Days alive and not hospitalized for CV reasons
measure: CV Death
time frame: 24 months
description: CV death by treatment arm
measure: Number of Hospitalizations for First Heart Failure
time frame: 24 months
description: First Heart Failure Hospitalization
measure: Number of Hospitalizations for Recurrent Heart Failure
time frame: 24 months
description: Recurrent Heart Failure Hospitalization
measure: Percentage of Patients With Moderate to Severe Depression
time frame: Baseline, 3,6, 12 and 24 months
description: Percentage of patients with moderate to severe depression as measured by the Center for Epidemiologic Studies Depression Scale (CES-D).
CES-D is a 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression. Moderate to severe depression is indicated by a score of 11 or higher.
measure: Duke Activity Status Index (DASI)
time frame: Baseline, 3, 6, 12 and 24 months
description: The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity).
measure: EQ-5D Health Index
time frame: Baseline, 3, 6, 12 and 24 months
description: The EQ-5D measures the subjects health status in 5 categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and totals them into 1 score, from -0.59 (worst) to 1 (best).
measure: EQ-5D Visual Analog Scale
time frame: Baseline, 3, 6, 12 and 24 months
description: The EQ-5D VAS records participants self-rated health status on a vertical (0-100) scale with higher scores indicating higher Health-Related Quality of Life, where 0 = worst imaginable health state and 100 = best imaginable health state.
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score
time frame: Baseline, 3, 6,12 and 24 months
description: This KCCQ overall score represents the mean of the following 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
measure: Short Form-36 (SF-36) General Health Subscale
time frame: Baseline, 3, 6, 12 and 24 months
description: SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.
measure: Short Form-36 (SF-36) Mental Health Subscale
time frame: Baseline, 3, 6, 12 and 24 months
description: SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.
measure: Short Form-36 (SF-36) Social Functioning Subscale
time frame: Baseline, 3, 6, 12 and 24 months
description: SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.
measure: Short Form-36 (SF-36) Physiological Functioning Subscale
time frame: Baseline, 3, 6, 12 and 24 months
description: SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.
measure: Short Form-36 (SF-36) Vitality Subscale
time frame: Baseline, 3, 6, 12 and 24 months
description: SF-36 measures perceived Quality of Life. The following subscales were used: General Health, Mental Health, Social Functioning, Physiological Functioning, and Vitality Each subscale is scored from 0-100 with 0 indicating lowest quality of life.
measure: Resource Utilization
time frame: 24 months
description: Observed Resource Use
measure: Resource Utilization Cost
time frame: 24 months
description: Observed Hospital-Based Cost.
arm group label: Usual Care
arm group type: Experimental
description: Usual Care group will receive standard heart failure treatment based on the doctor's best judgment and following the recommendation of current guidelines. This will typically include the use of medicines such as beta-blockers, ACE-inhibitors, and diuretics, all of which are approved, recommended treatments for heart failure.
arm group label: Biomarker-Guided Care
arm group type: Experimental
description: Device: Biomarker-Guided care NT-proBNP The Biomarker Guided Therapy group will receive the standard heart failure treatments. In addition, the doctor will use the results of a blood test called NT-proBNP to help adjust the treatments and drug doses.
intervention type: Other
intervention name: Usual Care
description: Usual Care
arm group label: Usual Care
intervention type: Device
intervention name: Biomarker-guided care NT-proBNP
description: Device: NT-proBNP
arm group label: Biomarker-Guided Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Felker, MD
role: Principal Investigator
affiliation: Duke University
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Heart Failure
participant flow: 
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reported events: 
certain agreements: 
point of contact: 