<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/NCT02196038</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00028221</org_study_id>
    <secondary_id>R01AG045551</secondary_id>
    <nct_id>NCT02196038</nct_id>
  </id_info>
  <brief_title>A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients</brief_title>
  <acronym>REHAB-HF</acronym>
  <official_title>REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients, is a&#xD;
      multicenter, randomized, attention-controlled, single-blind trial designed to examine the&#xD;
      hypothesis that, in addition to standard care, a novel, tailored, progressive, multi-domain&#xD;
      rehabilitation intervention administered to older patients with acute decompensated heart&#xD;
      failure (ADHF) beginning early during hospitalization and continuing for 12 weeks will&#xD;
      improve physical function and key clinical outcomes, including the rate of rehospitalization.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There will be three lead centers, Wake Forest Baptist Health along with Thomas Jefferson&#xD;
      University and Hospital-Co-Investigator Dr. David Whellan, and Duke University Medical&#xD;
      Center-Co-Investigator Dr. Christopher O'Connor. Each center may recruit up to 3&#xD;
      geographically close, tightly affiliated 'satellite' sites under their management and&#xD;
      budgetary control. Together, these sites will recruit a total of 352 consenting patients ≥ 60&#xD;
      years old hospitalized with ADHF. Following informed consent and baseline testing, the&#xD;
      participants will be randomized in a 1:1 fashion to receive a 12-week novel, progressive,&#xD;
      multi-domain rehabilitation and exercise training intervention or attention control. The&#xD;
      multi-domain rehabilitation intervention will include endurance, mobility, strength, and&#xD;
      balance training and will be tailored based on participant performance in each of these&#xD;
      domains. It will begin upon randomization during the hospitalization and will continue 3&#xD;
      times per week in an outpatient setting. Participants randomized to the attention control arm&#xD;
      will receive all services ordered by their primary physician and will be contacted bi-weekly&#xD;
      by study staff. All participants will undergo measures of physical function and quality of&#xD;
      life at baseline, 1 month, and 3 months. Clinical events will be monitored for 6 months&#xD;
      following the index hospitalization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">July 27, 2020</completion_date>
  <primary_completion_date type="Actual">June 15, 2020</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Short Physical Performance Battery (SPPB) at Month 3</measure>
    <time_frame>Month 3</time_frame>
    <description>The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-Cause Rehospitalization</measure>
    <time_frame>Month 6</time_frame>
    <description>Number of all-cause rehospitalizations 6 months from index hospital discharge.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>6-minute Walk Distance</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. Distance walked in 6 minutes.</description>
  </other_outcome>
  <other_outcome>
    <measure>Handgrip Strength</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. Handgrip strength is measured in kilograms by a handgrip dynamometer.</description>
  </other_outcome>
  <other_outcome>
    <measure>Frailty Status (Fried Frailty Criteria) at Month 3</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. Frailty is assessed by the Fried criteria consisting of 5 components: low physical activity, exhaustion, weakness, slowness, and unintentional weight loss. Presence of 3 or more Fried criteria indicates frailty, 1-2 criteria indicates pre-frailty, and 0 criteria indicates no frailty.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status.</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical Limitation as Assessed by the KCCQ Physical Limitation Score</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. The Physical Limitation Score of the KCCQ questionnaire is a subscore evaluating disease-specific physical limitation. Scores range 0-100 with a higher score indicating less physical limitation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12)</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. The SF-12 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Life Assessed by the EuroQol 5-dimension 5-level (EQ-5D-5L)</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. The EQ-5D-5L is a quality of life tool with 5 components designed to detect health utilities: mobility, usual activities, self-care, pain/discomfort, and anxiety/depression. All components are rated on a scale of 1-5 with higher scores indicating worse health status.</description>
  </other_outcome>
  <other_outcome>
    <measure>Depression Measured by the Geriatric Depression Scale</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. The Geriatric Depression Scale is a 15-item questionnaire evaluating depressive symptoms. Scores range from 0-15 with a higher score indicating more severe depressive symptoms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. The Montreal Cognitive Assessment is a tool for assessing multiple domains of cognitive function. Scores range 0-30 with higher scores indicating better cognitive function. A score greater than or equal to 26 is considered normal cognitive function.</description>
  </other_outcome>
  <other_outcome>
    <measure>All-cause Rehospitalizations at Month 1</measure>
    <time_frame>Month 1</time_frame>
    <description>Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge.</description>
  </other_outcome>
  <other_outcome>
    <measure>All-cause Rehospitalizations at Month 3</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>All-cause Combined Rehospitalization and Death at Month 6</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Combined number of all-cause rehospitalizations and death 6 months after discharge from index hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>Heart Failure Rehospitalizations at Month 6</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>Hospitalization Days Post-randomization</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Total days spent hospitalized after date of randomization.</description>
  </other_outcome>
  <other_outcome>
    <measure>Facility-free Days Alive</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcomes. Total days alive spent outside of hospital, observation unit, acute rehab setting, and skilled nursing facility 6 months after discharge from index hospitalization.</description>
  </other_outcome>
  <other_outcome>
    <measure>Emergency Department Visits</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcomes. Number of emergency department visits after 6 months from hospital discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Observation Unit Stays &lt;24 Hours</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Number of observation unit stays &lt;24 hours 6 months after discharge from index hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>Unscheduled Urgent Medical Visits</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>Global Rank Score of Short Physical Performance Battery Score + All-cause Rehospitalization + Death</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. The global rank composite outcome combines non-commensurate endpoints including death, number of all-cause rehospitalizations, and month 3 SPPB into a single non-parametric outcome in a hierarchical manner with death being ranked first and SPPB being ranked last. Participants are ranked from the most adverse response (lowest rank) to the most favorable response (highest rank).</description>
  </other_outcome>
  <other_outcome>
    <measure>Placement at Skilled Nursing Facility</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization.</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical Activity Assessed by Accelerometry</measure>
    <time_frame>Month 6</time_frame>
    <description>Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day.</description>
  </other_outcome>
  <other_outcome>
    <measure>Generalized Optimism Assessed by the Life Orientation Test-Revised</measure>
    <time_frame>Month 3</time_frame>
    <description>Exploratory outcome. The Life Orientation Test-Revised is a assessment of generalized optimism scored on a scale of 0-24 with higher scores indicating higher optimism.</description>
  </other_outcome>
  <other_outcome>
    <measure>Economic Analysis</measure>
    <time_frame>Month 6</time_frame>
    <description>Assess direct medical costs, direct non-medical costs, indirect patient time costs, short-term cost-analysis, long-term cost analysis, and sustainability of the intervention.</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Month 3</time_frame>
    <description>Two well-accepted biomarkers of HF disease severity and prognosis, NT-proBNP and galectin-3, and increased biomarkers in older HF patients Tumor necrosis factor alpha, C-reactive protein, and interleukin-6.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">349</enrollment>
  <condition>Acute Decompensated Heart Failure</condition>
  <arm_group>
    <arm_group_label>Attention Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Usual care group with bi-weekly contact from study staff</description>
  </arm_group>
  <arm_group>
    <arm_group_label>multi-domain rehabilitation intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Individual, tailored, progressive, physical function rehabilitation intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>multi-domain rehabilitation intervention</intervention_name>
    <description>Individual, tailored, progressive physical function rehabilitation intervention</description>
    <arm_group_label>multi-domain rehabilitation intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Attention Control</intervention_name>
    <description>Usual care with bi-weekly contact from study staff</description>
    <arm_group_label>Attention Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 60 years old&#xD;
&#xD;
          -  In the hospital setting &gt;24 hours for the management of ADHF, or diagnosed with ADHF&#xD;
             after being hospitalized for another reason. ADHF will be confirmed by the study&#xD;
             physician, and will be defined according to the Food and Drug Administration&#xD;
             definition of hospitalized heart failure as a combination of symptoms, signs, and&#xD;
             HF-specific medical treatments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute myocardial infarction&#xD;
&#xD;
          -  Planned discharge other than to home or a facility where the participant will live&#xD;
             independently&#xD;
&#xD;
          -  Already actively participating in formal, facility-based cardiac rehabilitation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dalane W. Kitzman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <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>Wake Forest Baptist Health</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University and Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>May 28, 2021</results_first_submitted>
  <results_first_submitted_qc>May 28, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2021</results_first_posted>
  <last_update_submitted>June 22, 2021</last_update_submitted>
  <last_update_submitted_qc>June 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2021</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT02196038/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT02196038/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Attention Control</title>
          <description>Usual care group with bi-weekly contact</description>
        </group>
        <group group_id="P2">
          <title>Rehabilitation Intervention</title>
          <description>Individual, tailored, progressive, multi-domain physical function rehabilitation intervention</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="174"/>
                <participants group_id="P2" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="157"/>
                <participants group_id="P2" count="153"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Attention Control</title>
          <description>Usual care group with bi-weekly contact</description>
        </group>
        <group group_id="B2">
          <title>Rehabilitation Intervention</title>
          <description>Individual, tailored, progressive, multi-domain physical function rehabilitation intervention</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="174"/>
            <count group_id="B2" value="175"/>
            <count group_id="B3" value="349"/>
          </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="72.2" spread="7.7"/>
                    <measurement group_id="B2" value="73.1" spread="8.5"/>
                    <measurement group_id="B3" value="72.7" spread="8.1"/>
                  </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="98"/>
                    <measurement group_id="B2" value="85"/>
                    <measurement group_id="B3" value="183"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="166"/>
                  </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="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="170"/>
                    <measurement group_id="B2" value="172"/>
                    <measurement group_id="B3" value="342"/>
                  </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="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="73"/>
                    <measurement group_id="B3" value="154"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="83"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="173"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </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>Short Physical Performance Battery</title>
          <description>The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.</description>
          <units>Score on a Scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.1" spread="2.6"/>
                    <measurement group_id="B2" value="6.0" spread="2.8"/>
                    <measurement group_id="B3" value="6.1" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Short Physical Performance Battery (SPPB) at Month 3</title>
        <description>The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.</description>
        <time_frame>Month 3</time_frame>
        <population>Analysis completed on all participants alive with Month 3 SPPB obtained (n=304).</population>
        <group_list>
          <group group_id="O1">
            <title>Attention Control</title>
            <description>Usual care group with bi-weekly contact</description>
          </group>
          <group group_id="O2">
            <title>Rehabilitation Intervention</title>
            <description>Individual, tailored, progressive, multi-domain physical function rehabilitation intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Short Physical Performance Battery (SPPB) at Month 3</title>
          <description>The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.</description>
          <population>Analysis completed on all participants alive with Month 3 SPPB obtained (n=304).</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="155"/>
                <count group_id="O2" value="149"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" spread="0.2"/>
                    <measurement group_id="O2" value="8.3" spread="0.2"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>joint model</method>
            <method_desc>Joint model of ANCOVA plus survival</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>All-Cause Rehospitalization</title>
        <description>Number of all-cause rehospitalizations 6 months from index hospital discharge.</description>
        <time_frame>Month 6</time_frame>
        <population>All participants, regardless of participation in the intervention or Month 3 follow-up were followed for all-cause rehospitalizations. Analysis completed on all participants, including deaths, except participants lost to follow-up (n=1) and participants withdrawn from study (n=1).</population>
        <group_list>
          <group group_id="O1">
            <title>Attention Control</title>
            <description>Usual care group with bi-weekly contact</description>
          </group>
          <group group_id="O2">
            <title>Rehabilitation Intervention</title>
            <description>Individual, tailored, progressive, multi-domain physical function rehabilitation intervention</description>
          </group>
        </group_list>
        <measure>
          <title>All-Cause Rehospitalization</title>
          <description>Number of all-cause rehospitalizations 6 months from index hospital discharge.</description>
          <population>All participants, regardless of participation in the intervention or Month 3 follow-up were followed for all-cause rehospitalizations. Analysis completed on all participants, including deaths, except participants lost to follow-up (n=1) and participants withdrawn from study (n=1).</population>
          <units>rehospitalizations</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="173"/>
                <count group_id="O2" value="174"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="213"/>
                    <measurement group_id="O2" value="194"/>
                  </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</non_inferiority_type>
            <p_value>0.59</p_value>
            <method>Joint Model</method>
            <method_desc>Joint model of Poisson regression and survival</method_desc>
            <param_type>Rate Ratio</param_type>
            <param_value>0.93</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.66</ci_lower_limit>
            <ci_upper_limit>1.19</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>6-minute Walk Distance</title>
        <description>Exploratory outcome. Distance walked in 6 minutes.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Handgrip Strength</title>
        <description>Exploratory outcome. Handgrip strength is measured in kilograms by a handgrip dynamometer.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Frailty Status (Fried Frailty Criteria) at Month 3</title>
        <description>Exploratory outcome. Frailty is assessed by the Fried criteria consisting of 5 components: low physical activity, exhaustion, weakness, slowness, and unintentional weight loss. Presence of 3 or more Fried criteria indicates frailty, 1-2 criteria indicates pre-frailty, and 0 criteria indicates no frailty.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score</title>
        <description>Exploratory outcome. The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Physical Limitation as Assessed by the KCCQ Physical Limitation Score</title>
        <description>Exploratory outcome. The Physical Limitation Score of the KCCQ questionnaire is a subscore evaluating disease-specific physical limitation. Scores range 0-100 with a higher score indicating less physical limitation.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12)</title>
        <description>Exploratory outcome. The SF-12 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Quality of Life Assessed by the EuroQol 5-dimension 5-level (EQ-5D-5L)</title>
        <description>Exploratory outcome. The EQ-5D-5L is a quality of life tool with 5 components designed to detect health utilities: mobility, usual activities, self-care, pain/discomfort, and anxiety/depression. All components are rated on a scale of 1-5 with higher scores indicating worse health status.</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Depression Measured by the Geriatric Depression Scale</title>
        <description>Exploratory outcome. The Geriatric Depression Scale is a 15-item questionnaire evaluating depressive symptoms. Scores range from 0-15 with a higher score indicating more severe depressive symptoms.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)</title>
        <description>Exploratory outcome. The Montreal Cognitive Assessment is a tool for assessing multiple domains of cognitive function. Scores range 0-30 with higher scores indicating better cognitive function. A score greater than or equal to 26 is considered normal cognitive function.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>All-cause Rehospitalizations at Month 1</title>
        <description>Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge.</description>
        <time_frame>Month 1</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>All-cause Rehospitalizations at Month 3</title>
        <description>Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>All-cause Combined Rehospitalization and Death at Month 6</title>
        <description>Exploratory outcome. Combined number of all-cause rehospitalizations and death 6 months after discharge from index hospitalization</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Heart Failure Rehospitalizations at Month 6</title>
        <description>Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hospitalization Days Post-randomization</title>
        <description>Exploratory outcome. Total days spent hospitalized after date of randomization.</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Facility-free Days Alive</title>
        <description>Exploratory outcomes. Total days alive spent outside of hospital, observation unit, acute rehab setting, and skilled nursing facility 6 months after discharge from index hospitalization.</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Emergency Department Visits</title>
        <description>Exploratory outcomes. Number of emergency department visits after 6 months from hospital discharge</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Observation Unit Stays &lt;24 Hours</title>
        <description>Exploratory outcome. Number of observation unit stays &lt;24 hours 6 months after discharge from index hospitalization</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Unscheduled Urgent Medical Visits</title>
        <description>Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Global Rank Score of Short Physical Performance Battery Score + All-cause Rehospitalization + Death</title>
        <description>Exploratory outcome. The global rank composite outcome combines non-commensurate endpoints including death, number of all-cause rehospitalizations, and month 3 SPPB into a single non-parametric outcome in a hierarchical manner with death being ranked first and SPPB being ranked last. Participants are ranked from the most adverse response (lowest rank) to the most favorable response (highest rank).</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Placement at Skilled Nursing Facility</title>
        <description>Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization.</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Physical Activity Assessed by Accelerometry</title>
        <description>Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day.</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Generalized Optimism Assessed by the Life Orientation Test-Revised</title>
        <description>Exploratory outcome. The Life Orientation Test-Revised is a assessment of generalized optimism scored on a scale of 0-24 with higher scores indicating higher optimism.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Economic Analysis</title>
        <description>Assess direct medical costs, direct non-medical costs, indirect patient time costs, short-term cost-analysis, long-term cost analysis, and sustainability of the intervention.</description>
        <time_frame>Month 6</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Biomarkers</title>
        <description>Two well-accepted biomarkers of HF disease severity and prognosis, NT-proBNP and galectin-3, and increased biomarkers in older HF patients Tumor necrosis factor alpha, C-reactive protein, and interleukin-6.</description>
        <time_frame>Month 3</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs collected from date of discharge from index hospitalization through Month 6.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Attention Control</title>
          <description>Usual care group with bi-weekly contact</description>
        </group>
        <group group_id="E2">
          <title>Rehabilitation Intervention</title>
          <description>Individual, tailored, progressive, multi-domain physical function rehabilitation intervention</description>
        </group>
      </group_list>
      <serious_events>
        <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="16" subjects_at_risk="174"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="115" subjects_at_risk="174"/>
                <counts group_id="E2" subjects_affected="106" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>epitaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>aortic valve disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>atrial flutter</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>heart failure exacerbation</sub_title>
                <counts group_id="E1" events="107" subjects_affected="64" subjects_at_risk="174"/>
                <counts group_id="E2" events="99" subjects_affected="57" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>mitral stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>mitral valve repair</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>myocardial infarction</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>sudden cardiac death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>ventricular tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>colonic fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>duodenal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>gastrointestinal bleed</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>gastroparesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>multiple organ failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>small bowel obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="174"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hepatotoxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>liver cirrhosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>primary amyloidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>bacterial endocarditis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>osteomyelitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>upper respiratory infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>wound infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>injurious fall</sub_title>
                <counts group_id="E1" events="18" subjects_affected="16" subjects_at_risk="174"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>intracranial hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>oxycontin overdose</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>serotonin syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>spinal compression fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>tacrolimus toxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypoglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>gout flare</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>chronic lymphocytic leukemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>metastatic cancer</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pancreatic adenocarcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>dysarthia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>stroke</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="174"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>syncope</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>transient ischemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>sucidal ideation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>acute kidney injury</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>vaginal discharge</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COPD exacerbation</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>dyspnea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>interstitial lung disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pleural effusion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pulmonary edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pulmonary fibrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>diabetic foot ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>ablation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>arteriovenous fistula placement</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>bronchoscopy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>cateract surgery</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>implantable cardioverter defibrillator implantation</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pacemaker implantation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>remodulin pump implantation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>renal artery angioplasty</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>hematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypotension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="69" subjects_at_risk="174"/>
                <counts group_id="E2" subjects_affected="60" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>elevated international normalized ratio</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>epitaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>heart failure exacerbation</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="174"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>suprventricular tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>sudden vision loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>gastrointestinal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>melena</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="174"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>upper respiratory infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>abrasion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>compression fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>ear injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>fall (self-reported)</sub_title>
                <counts group_id="E1" events="112" subjects_affected="62" subjects_at_risk="174"/>
                <counts group_id="E2" events="94" subjects_affected="48" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>foot wound</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>ICD device complications</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>post-prodecural complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>fluid retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypoglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>gout flare</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>muscle strain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>musculoskeletal pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="174"/>
                <counts group_id="E2" events="13" subjects_affected="10" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>altered mental status</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>elevated creatinine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>kidney stone</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>urinary retention</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COPD exacerbation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>skin lesion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="174"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>venous stasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="174"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </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>Dr. Dalane Kitzman</name_or_title>
      <organization>Wake Forest School of Medicine</organization>
      <phone>336-716-3274</phone>
      <email>dkitzman@wakehealth.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/NCT02196038
org study id: IRB00028221
secondary id: R01AG045551
nct id: NCT02196038
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients, is a
      multicenter, randomized, attention-controlled, single-blind trial designed to examine the
      hypothesis that, in addition to standard care, a novel, tailored, progressive, multi-domain
      rehabilitation intervention administered to older patients with acute decompensated heart
      failure (ADHF) beginning early during hospitalization and continuing for 12 weeks will
      improve physical function and key clinical outcomes, including the rate of rehospitalization.
There will be three lead centers, Wake Forest Baptist Health along with Thomas Jefferson
      University and Hospital-Co-Investigator Dr. David Whellan, and Duke University Medical
      Center-Co-Investigator Dr. Christopher O'Connor. Each center may recruit up to 3
      geographically close, tightly affiliated 'satellite' sites under their management and
      budgetary control. Together, these sites will recruit a total of 352 consenting patients ≥ 60
      years old hospitalized with ADHF. Following informed consent and baseline testing, the
      participants will be randomized in a 1:1 fashion to receive a 12-week novel, progressive,
      multi-domain rehabilitation and exercise training intervention or attention control. The
      multi-domain rehabilitation intervention will include endurance, mobility, strength, and
      balance training and will be tailored based on participant performance in each of these
      domains. It will begin upon randomization during the hospitalization and will continue 3
      times per week in an outpatient setting. Participants randomized to the attention control arm
      will receive all services ordered by their primary physician and will be contacted bi-weekly
      by study staff. All participants will undergo measures of physical function and quality of
      life at baseline, 1 month, and 3 months. Clinical events will be monitored for 6 months
      following the index hospitalization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Short Physical Performance Battery (SPPB) at Month 3
time frame: Month 3
description: The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.
measure: All-Cause Rehospitalization
time frame: Month 6
description: Number of all-cause rehospitalizations 6 months from index hospital discharge.
measure: 6-minute Walk Distance
time frame: Month 3
description: Exploratory outcome. Distance walked in 6 minutes.
measure: Handgrip Strength
time frame: Month 3
description: Exploratory outcome. Handgrip strength is measured in kilograms by a handgrip dynamometer.
measure: Frailty Status (Fried Frailty Criteria) at Month 3
time frame: Month 3
description: Exploratory outcome. Frailty is assessed by the Fried criteria consisting of 5 components: low physical activity, exhaustion, weakness, slowness, and unintentional weight loss. Presence of 3 or more Fried criteria indicates frailty, 1-2 criteria indicates pre-frailty, and 0 criteria indicates no frailty.
measure: Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
time frame: Month 3
description: Exploratory outcome. The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status.
measure: Physical Limitation as Assessed by the KCCQ Physical Limitation Score
time frame: Month 3
description: Exploratory outcome. The Physical Limitation Score of the KCCQ questionnaire is a subscore evaluating disease-specific physical limitation. Scores range 0-100 with a higher score indicating less physical limitation.
measure: Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12)
time frame: Month 3
description: Exploratory outcome. The SF-12 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status.
measure: Quality of Life Assessed by the EuroQol 5-dimension 5-level (EQ-5D-5L)
time frame: Month 6
description: Exploratory outcome. The EQ-5D-5L is a quality of life tool with 5 components designed to detect health utilities: mobility, usual activities, self-care, pain/discomfort, and anxiety/depression. All components are rated on a scale of 1-5 with higher scores indicating worse health status.
measure: Depression Measured by the Geriatric Depression Scale
time frame: Month 3
description: Exploratory outcome. The Geriatric Depression Scale is a 15-item questionnaire evaluating depressive symptoms. Scores range from 0-15 with a higher score indicating more severe depressive symptoms.
measure: Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)
time frame: Month 3
description: Exploratory outcome. The Montreal Cognitive Assessment is a tool for assessing multiple domains of cognitive function. Scores range 0-30 with higher scores indicating better cognitive function. A score greater than or equal to 26 is considered normal cognitive function.
measure: All-cause Rehospitalizations at Month 1
time frame: Month 1
description: Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge.
measure: All-cause Rehospitalizations at Month 3
time frame: Month 3
description: Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization
measure: All-cause Combined Rehospitalization and Death at Month 6
time frame: Month 6
description: Exploratory outcome. Combined number of all-cause rehospitalizations and death 6 months after discharge from index hospitalization
measure: Heart Failure Rehospitalizations at Month 6
time frame: Month 6
description: Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization
measure: Hospitalization Days Post-randomization
time frame: Month 6
description: Exploratory outcome. Total days spent hospitalized after date of randomization.
measure: Facility-free Days Alive
time frame: Month 6
description: Exploratory outcomes. Total days alive spent outside of hospital, observation unit, acute rehab setting, and skilled nursing facility 6 months after discharge from index hospitalization.
measure: Emergency Department Visits
time frame: Month 6
description: Exploratory outcomes. Number of emergency department visits after 6 months from hospital discharge
measure: Observation Unit Stays <24 Hours
time frame: Month 6
description: Exploratory outcome. Number of observation unit stays <24 hours 6 months after discharge from index hospitalization
measure: Unscheduled Urgent Medical Visits
time frame: Month 6
description: Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization
measure: Global Rank Score of Short Physical Performance Battery Score + All-cause Rehospitalization + Death
time frame: Month 6
description: Exploratory outcome. The global rank composite outcome combines non-commensurate endpoints including death, number of all-cause rehospitalizations, and month 3 SPPB into a single non-parametric outcome in a hierarchical manner with death being ranked first and SPPB being ranked last. Participants are ranked from the most adverse response (lowest rank) to the most favorable response (highest rank).
measure: Placement at Skilled Nursing Facility
time frame: Month 6
description: Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization.
measure: Physical Activity Assessed by Accelerometry
time frame: Month 6
description: Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day.
measure: Generalized Optimism Assessed by the Life Orientation Test-Revised
time frame: Month 3
description: Exploratory outcome. The Life Orientation Test-Revised is a assessment of generalized optimism scored on a scale of 0-24 with higher scores indicating higher optimism.
measure: Economic Analysis
time frame: Month 6
description: Assess direct medical costs, direct non-medical costs, indirect patient time costs, short-term cost-analysis, long-term cost analysis, and sustainability of the intervention.
measure: Biomarkers
time frame: Month 3
description: Two well-accepted biomarkers of HF disease severity and prognosis, NT-proBNP and galectin-3, and increased biomarkers in older HF patients Tumor necrosis factor alpha, C-reactive protein, and interleukin-6.
arm group label: Attention Control
arm group type: Other
description: Usual care group with bi-weekly contact from study staff
arm group label: multi-domain rehabilitation intervention
arm group type: Active Comparator
description: Individual, tailored, progressive, physical function rehabilitation intervention
intervention type: Behavioral
intervention name: multi-domain rehabilitation intervention
description: Individual, tailored, progressive physical function rehabilitation intervention
arm group label: multi-domain rehabilitation intervention
intervention type: Behavioral
intervention name: Attention Control
description: Usual care with bi-weekly contact from study staff
arm group label: Attention Control
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Dalane W. Kitzman, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 