<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/NCT02237911</url>
  </required_header>
  <id_info>
    <org_study_id>PRO14080261</org_study_id>
    <secondary_id>CER-1310-06994</secondary_id>
    <nct_id>NCT02237911</nct_id>
  </id_info>
  <brief_title>Comparison of Treatments Following Total Knee Replacement</brief_title>
  <official_title>A Comparison of Treatment Methods for Patients Following Total Knee Replacement.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Patient-Centered Outcomes Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although total knee replacement (TKR) improves pain in numerous patients, it does not resolve&#xD;
      many of the substantial functional limitations and physical inactivity that existed for a&#xD;
      long time prior to the surgery. Exercise is an intervention that could improve these&#xD;
      long-term limitations. To promote these improvements, exercise should be implemented at later&#xD;
      stage post TKR when patients can tolerate doses of exercise sufficiently high to promote&#xD;
      substantial changes. To date, we just don't have enough good research to tell us which type&#xD;
      of exercise works best for which patients and under which circumstances at later stage post&#xD;
      TKR. This research study will provide evidence for recommended interventions during the later&#xD;
      stage post TKR. The specific research questions are: (1) How do group exercise in the&#xD;
      community and individual exercise in rehabilitation clinic compare with usual medical care on&#xD;
      physical function and activity outcomes? (2) Who are the patients most likely to respond to&#xD;
      each exercise intervention? (3) Are the approaches safe?&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a comparative effectiveness study, designed as a 3-group single-blind randomized&#xD;
      clinical trial. Two hundred forty older adults who underwent TKR at least 2 months prior and&#xD;
      are otherwise eligible will be randomized into one of three treatment approaches: 1)&#xD;
      clinic-based individual outpatient rehabilitative exercise; 2) community-based group exercise&#xD;
      classes; or 3) usual medical care. Subjects will be treated for 3 months. Data will be&#xD;
      collected before intervention, after intervention (3 months), and 6 months after&#xD;
      randomization. Physical function is a primary outcome and will be assessed by the Western&#xD;
      Ontario and McMaster Universities Arthritis Index and a battery of performance-based tests&#xD;
      germane to patients post TKR that includes ability to walk, manage stairs, lift from the&#xD;
      floor and the chair, and one-leg balance. We will also use an accelerometer-based monitor&#xD;
      that provides a real-time measure of physical activity during normal daily living and is able&#xD;
      to accurately capture most levels of activity. Linear mixed models will be fitted to compare&#xD;
      the changes in outcome across groups. Logistic regression will identify patient&#xD;
      characteristics that predict functional recovery in the exercise groups. Survival analysis&#xD;
      and instrumental variable methods will be used to compare attrition, adherence and adverse&#xD;
      events between groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">September 7, 2017</completion_date>
  <primary_completion_date type="Actual">September 7, 2017</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>The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF).</measure>
    <time_frame>Baseline, 3 and 6 months</time_frame>
    <description>WOMAC-PF is a patient reported outcome with 17 items. Each item is scored on a 5-point Likert-type Scale with descriptors from 0-4 (none, mild, moderate, severe, and extreme difficulty) and summed for a maximum score of 68. Higher scores indicate worse physical function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite Score of Performed-based Tests of Physical Function.</measure>
    <time_frame>Baseline, 3 and 6 months</time_frame>
    <description>Scores on 6 performance-based tests (i.e., the 6-minute walk test, 40-meter gait speed, stair ascend/descend test, single leg stance balance test, chair stand test, and floor sitting-rising) were combined into a composite score formed with the unit-weighted Z scores of constituent tests to provide a more representative and stable measure of the subjects' underlying functional performance. The unit weights refer to averaging standardized scores (e.g., the scores for each performance-based test are converted to Z-scores before applying equal weights). Higher Z-scores represent better functional performance. The Z-scores for each participant can be interpreted as deviations from the baseline average of the whole group. We considered a change in Z-score of 0.2 as clinically important because it represents approximately 20% of a standard deviation relative to the baseline average of the whole group.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear).</measure>
    <time_frame>Baseline, 3 and 6 months</time_frame>
    <description>Real-time measure of daily energy expenditure physical activity assessed by portable activity monitor.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">240</enrollment>
  <condition>Degeneration; Articular Cartilage, Knee</condition>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>Clinic-based outpatient exercise group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will participate in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session will last about 60 minutes. Treatment sessions will utilize a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Community-based exercise group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will attend to exercise classes (community-based) 2 times per week during 3 months. The exercise classes last approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Wait-listed usual medical care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Wait-listed usual medical care - no intervention provided by study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinic-based outpatient exercise group</intervention_name>
    <description>Subjects will participate in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session will last about 60 minutes. Treatment sessions will utilize a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
    <arm_group_label>Clinic-based outpatient exercise group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Community-based exercise group</intervention_name>
    <description>Subjects will attend to exercise classes (community-based) 2 times per week during 3 months. The exercise classes last approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
    <arm_group_label>Community-based exercise group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unilateral TKR 2 to 4 months prior&#xD;
&#xD;
          -  Older than 60 years of age&#xD;
&#xD;
          -  Experience functional limitation in daily activities (score in WOMAC-PF of at least 9&#xD;
             points)&#xD;
&#xD;
          -  Speak sufficient English to understand study instructions&#xD;
&#xD;
          -  Have medical clearance to participate in the study&#xD;
&#xD;
          -  Are willing to be randomized to one of the 3 treatment arms&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have absolute or relative contraindications to exercise&#xD;
&#xD;
          -  Have history of uncontrolled cardiovascular disease or hypertension&#xD;
&#xD;
          -  Are unable to walk 50 meters without an assistive device&#xD;
&#xD;
          -  Have history of muscular or neurological disorder that affect lower extremity function&#xD;
&#xD;
          -  Regular participation in exercise&#xD;
&#xD;
          -  Terminal illness&#xD;
&#xD;
          -  Planning to have another joint replacement during the next 12 months&#xD;
&#xD;
          -  Plan not to be around during the next 12 months&#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>Sara R Piva, PT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Physical Therapy, University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <results_first_submitted>December 31, 2017</results_first_submitted>
  <results_first_submitted_qc>November 16, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 11, 2019</results_first_posted>
  <last_update_submitted>November 16, 2018</last_update_submitted>
  <last_update_submitted_qc>November 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Sara R. Piva</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>total knee replacement</keyword>
  <keyword>rehabilitation</keyword>
  <keyword>exercise program</keyword>
  <keyword>total knee arthroplasty</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <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>August 31, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT02237911/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Potential subjects were identified from their surgeons' office or via public announcement in the greater Pittsburgh area, from December 2014 through February 2017. If interested in the study, subjects called the research team to obtain more information about the study, and were then screened for study eligibility.</recruitment_details>
      <pre_assignment_details>A total of 1372 subjects called for study information: 89 could not be contacted and 1283 were screened over the telephone. From those, 1032 were not eligible/willing to participate and 251 completed in-person screening. Eleven subjects failed in-person screening, resulting in 240 eligible subjects that were randomized into one of the study arms.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Clinic-based Outpatient Exercise Group</title>
          <description>Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and included the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
        </group>
        <group group_id="P2">
          <title>Community-based Exercise Group</title>
          <description>Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consisted of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
        </group>
        <group group_id="P3">
          <title>Wait-listed Usual Medical Care</title>
          <description>Wait-listed usual medical care - no intervention provided by study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
                <participants group_id="P2" count="96"/>
                <participants group_id="P3" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>3 Months</title>
              <participants_list>
                <participants group_id="P1" count="90"/>
                <participants group_id="P2" count="87"/>
                <participants group_id="P3" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>6 Months</title>
              <participants_list>
                <participants group_id="P1" count="89"/>
                <participants group_id="P2" count="88"/>
                <participants group_id="P3" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="89"/>
                <participants group_id="P2" count="88"/>
                <participants group_id="P3" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Clinic-based Outpatient Exercise Group</title>
          <description>Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and included exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
        </group>
        <group group_id="B2">
          <title>Community-based Exercise Group</title>
          <description>Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consisted of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
        </group>
        <group group_id="B3">
          <title>Wait-listed Usual Medical Care</title>
          <description>Wait-listed usual medical care - no intervention provided by study.</description>
        </group>
        <group group_id="B4">
          <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="96"/>
            <count group_id="B2" value="96"/>
            <count group_id="B3" value="48"/>
            <count group_id="B4" value="240"/>
          </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="69" spread="6.3"/>
                    <measurement group_id="B2" value="70" spread="7.0"/>
                    <measurement group_id="B3" value="70" spread="6.6"/>
                    <measurement group_id="B4" value="70" spread="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="148"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="92"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="96"/>
                    <measurement group_id="B2" value="95"/>
                    <measurement group_id="B3" value="47"/>
                    <measurement group_id="B4" value="238"/>
                  </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 group_id="B4" 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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="86"/>
                    <measurement group_id="B2" value="77"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="200"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Less than college</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete college or technical training</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="57"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other/missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Marital status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Married</title>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="62"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="157"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Divorced</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Widowed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Never Married</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.8" spread="5.3"/>
                    <measurement group_id="B2" value="31.1" spread="6.3"/>
                    <measurement group_id="B3" value="31.5" spread="5.1"/>
                    <measurement group_id="B4" value="31.1" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cumulative Illness Rating Scale</title>
          <units>Number of comorbidities</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.3" spread="2.0"/>
                    <measurement group_id="B2" value="4.4" spread="1.7"/>
                    <measurement group_id="B3" value="4.6" spread="1.9"/>
                    <measurement group_id="B4" value="4.4" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total Knee Replacement Due To</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Osteoarthritis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="92"/>
                    <measurement group_id="B3" value="48"/>
                    <measurement group_id="B4" value="232"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Inflammatory Arthritis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Surgical Knee Flexion</title>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="124" spread="11"/>
                    <measurement group_id="B2" value="123" spread="11"/>
                    <measurement group_id="B3" value="124" spread="10"/>
                    <measurement group_id="B4" value="124" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Surgical knee pain</title>
          <description>Numeric Pain Rating Scale (NPRS). Current pain intensity was measure by NRPS. Score ranged from 0 to 10, 0 representing no pain, and 10 representing worse pain imaginable.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.7" spread="2.1"/>
                    <measurement group_id="B2" value="2.3" spread="1.7"/>
                    <measurement group_id="B3" value="2.2" spread="1.8"/>
                    <measurement group_id="B4" value="2.4" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF).</title>
        <description>WOMAC-PF is a patient reported outcome with 17 items. Each item is scored on a 5-point Likert-type Scale with descriptors from 0-4 (none, mild, moderate, severe, and extreme difficulty) and summed for a maximum score of 68. Higher scores indicate worse physical function.</description>
        <time_frame>Baseline, 3 and 6 months</time_frame>
        <population>Intention-to-treat approach was used among participants with follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Clinic-based Outpatient Exercise Group</title>
            <description>Clinic-based outpatient exercise group: Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
          </group>
          <group group_id="O2">
            <title>Community-based Exercise Group</title>
            <description>Community-based exercise group: Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
          </group>
          <group group_id="O3">
            <title>Wait-listed Usual Medical Care</title>
            <description>Wait-listed usual medical care - no intervention provided by study.</description>
          </group>
        </group_list>
        <measure>
          <title>The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF).</title>
          <description>WOMAC-PF is a patient reported outcome with 17 items. Each item is scored on a 5-point Likert-type Scale with descriptors from 0-4 (none, mild, moderate, severe, and extreme difficulty) and summed for a maximum score of 68. Higher scores indicate worse physical function.</description>
          <population>Intention-to-treat approach was used among participants with follow-up data.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="96"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="96"/>
                    <count group_id="O3" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.9" spread="7.9"/>
                    <measurement group_id="O2" value="20.4" spread="7.4"/>
                    <measurement group_id="O3" value="20.2" spread="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="90"/>
                    <count group_id="O2" value="87"/>
                    <count group_id="O3" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.1" spread="6.6"/>
                    <measurement group_id="O2" value="12.2" spread="7.9"/>
                    <measurement group_id="O3" value="11.9" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                    <count group_id="O2" value="88"/>
                    <count group_id="O3" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="7.2"/>
                    <measurement group_id="O2" value="10.8" spread="7.9"/>
                    <measurement group_id="O3" value="11.8" spread="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.071</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.1</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.9</ci_lower_limit>
            <ci_upper_limit>0.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Contrasts from a linear mixed models analysis at 6 months adjusted by baseline age, gender, BMI, WOMAC-PF, knee flexion.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.074</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.1</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.0</ci_lower_limit>
            <ci_upper_limit>0.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Contrasts from a linear mixed models analysis at 3 months adjusted by baseline age, gender, BMI, WOMAC-PF, knee flexion.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.930</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.1</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.7</ci_lower_limit>
            <ci_upper_limit>2.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.491</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.7</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
          <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>0.021</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.2</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.5</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
          </analysis>
          <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>0.179</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.3</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.6</ci_lower_limit>
            <ci_upper_limit>1.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Score of Performed-based Tests of Physical Function.</title>
        <description>Scores on 6 performance-based tests (i.e., the 6-minute walk test, 40-meter gait speed, stair ascend/descend test, single leg stance balance test, chair stand test, and floor sitting-rising) were combined into a composite score formed with the unit-weighted Z scores of constituent tests to provide a more representative and stable measure of the subjects' underlying functional performance. The unit weights refer to averaging standardized scores (e.g., the scores for each performance-based test are converted to Z-scores before applying equal weights). Higher Z-scores represent better functional performance. The Z-scores for each participant can be interpreted as deviations from the baseline average of the whole group. We considered a change in Z-score of 0.2 as clinically important because it represents approximately 20% of a standard deviation relative to the baseline average of the whole group.</description>
        <time_frame>Baseline, 3 and 6 months</time_frame>
        <population>Intention-to-treat approach was used among participants with follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Clinic-based Outpatient Exercise Group</title>
            <description>Clinic-based outpatient exercise group: Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
          </group>
          <group group_id="O2">
            <title>Community-based Exercise Group</title>
            <description>Community-based exercise group: Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
          </group>
          <group group_id="O3">
            <title>Wait-listed Usual Medical Care</title>
            <description>Wait-listed usual medical care - no intervention provided by study.</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Score of Performed-based Tests of Physical Function.</title>
          <description>Scores on 6 performance-based tests (i.e., the 6-minute walk test, 40-meter gait speed, stair ascend/descend test, single leg stance balance test, chair stand test, and floor sitting-rising) were combined into a composite score formed with the unit-weighted Z scores of constituent tests to provide a more representative and stable measure of the subjects' underlying functional performance. The unit weights refer to averaging standardized scores (e.g., the scores for each performance-based test are converted to Z-scores before applying equal weights). Higher Z-scores represent better functional performance. The Z-scores for each participant can be interpreted as deviations from the baseline average of the whole group. We considered a change in Z-score of 0.2 as clinically important because it represents approximately 20% of a standard deviation relative to the baseline average of the whole group.</description>
          <population>Intention-to-treat approach was used among participants with follow-up data.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="96"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="96"/>
                    <count group_id="O3" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02" spread="0.8"/>
                    <measurement group_id="O2" value="-0.06" spread="0.8"/>
                    <measurement group_id="O3" value="-0.11" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                    <count group_id="O2" value="87"/>
                    <count group_id="O3" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49" spread="0.7"/>
                    <measurement group_id="O2" value="0.3" spread="0.8"/>
                    <measurement group_id="O3" value="0.13" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="76"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.8"/>
                    <measurement group_id="O2" value="0.36" spread="0.9"/>
                    <measurement group_id="O3" value="0.25" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.3</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1</ci_lower_limit>
            <ci_upper_limit>0.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.012</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.2</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.01</ci_lower_limit>
            <ci_upper_limit>0.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.2</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.02</ci_lower_limit>
            <ci_upper_limit>0.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.052</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.2</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.003</ci_lower_limit>
            <ci_upper_limit>0.3</ci_upper_limit>
          </analysis>
          <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>0.015</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.2</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.02</ci_lower_limit>
            <ci_upper_limit>0.3</ci_upper_limit>
          </analysis>
          <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>0.489</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.02</param_value>
            <ci_percent>98.3</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.003</ci_lower_limit>
            <ci_upper_limit>0.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear).</title>
        <description>Real-time measure of daily energy expenditure physical activity assessed by portable activity monitor.</description>
        <time_frame>Baseline, 3 and 6 months</time_frame>
        <population>Intention-to-treat approach was used among participants with follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Clinic-based Outpatient Exercise Group</title>
            <description>Clinic-based outpatient exercise group: Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
          </group>
          <group group_id="O2">
            <title>Community-based Exercise Group</title>
            <description>Community-based exercise group: Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
          </group>
          <group group_id="O3">
            <title>Wait-listed Usual Medical Care</title>
            <description>Wait-listed usual medical care - no intervention provided by study.</description>
          </group>
        </group_list>
        <measure>
          <title>Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear).</title>
          <description>Real-time measure of daily energy expenditure physical activity assessed by portable activity monitor.</description>
          <population>Intention-to-treat approach was used among participants with follow-up data.</population>
          <units>Kcal/day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="96"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="95"/>
                    <count group_id="O3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="511" spread="411"/>
                    <measurement group_id="O2" value="541" spread="419"/>
                    <measurement group_id="O3" value="459" spread="352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="85"/>
                    <count group_id="O2" value="86"/>
                    <count group_id="O3" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="566" spread="451"/>
                    <measurement group_id="O2" value="547" spread="407"/>
                    <measurement group_id="O3" value="525" spread="411"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="84"/>
                    <count group_id="O2" value="79"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="538" spread="403"/>
                    <measurement group_id="O2" value="480" spread="420"/>
                    <measurement group_id="O3" value="509" spread="518"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.943</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-106</ci_lower_limit>
            <ci_upper_limit>114</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.814</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-112</ci_lower_limit>
            <ci_upper_limit>142</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.787</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-125</ci_lower_limit>
            <ci_upper_limit>95</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.581</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-164</ci_lower_limit>
            <ci_upper_limit>92</ci_upper_limit>
          </analysis>
          <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>0.676</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 3 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>19</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-71</ci_lower_limit>
            <ci_upper_limit>109</ci_upper_limit>
          </analysis>
          <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>0.330</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Contrasts from a linear mixed models analysis at 6 months adjusted for randomization factors (age, gender, BMI, WOMAC-PF, knee flexion).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-52</ci_lower_limit>
            <ci_upper_limit>154</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The adverse events were collected during subjects participation in the study (over 6 months).</time_frame>
      <desc>The study used a standard questionnaire to monitor AEs every 1.5 months.</desc>
      <group_list>
        <group group_id="E1">
          <title>Clinic-based Outpatient Exercise Group</title>
          <description>Clinic-based outpatient exercise group: Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.</description>
        </group>
        <group group_id="E2">
          <title>Community-based Exercise Group</title>
          <description>Community-based exercise group: Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.</description>
        </group>
        <group group_id="E3">
          <title>Wait-listed Usual Medical Care</title>
          <description>Wait-listed usual medical care - no intervention provided by study.</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="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroesophageal Reflux Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Injury, poisoning and procedural complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep apnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="18" subjects_at_risk="96"/>
                <counts group_id="E2" events="18" subjects_affected="17" subjects_at_risk="96"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="96"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="96"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Other musculoskeletal and connective tissue disorder</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="96"/>
                <counts group_id="E2" events="13" subjects_affected="13" subjects_at_risk="96"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="48"/>
              </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. Sara Piva</name_or_title>
      <organization>University of Pittsburgh</organization>
      <phone>(412) 383-6712</phone>
      <email>spiva@pitt.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/NCT02237911
org study id: PRO14080261
secondary id: CER-1310-06994
nct id: NCT02237911
lead sponsor: 
collaborator: 
has dmc: Yes
Although total knee replacement (TKR) improves pain in numerous patients, it does not resolve
      many of the substantial functional limitations and physical inactivity that existed for a
      long time prior to the surgery. Exercise is an intervention that could improve these
      long-term limitations. To promote these improvements, exercise should be implemented at later
      stage post TKR when patients can tolerate doses of exercise sufficiently high to promote
      substantial changes. To date, we just don't have enough good research to tell us which type
      of exercise works best for which patients and under which circumstances at later stage post
      TKR. This research study will provide evidence for recommended interventions during the later
      stage post TKR. The specific research questions are: (1) How do group exercise in the
      community and individual exercise in rehabilitation clinic compare with usual medical care on
      physical function and activity outcomes? (2) Who are the patients most likely to respond to
      each exercise intervention? (3) Are the approaches safe?
This is a comparative effectiveness study, designed as a 3-group single-blind randomized
      clinical trial. Two hundred forty older adults who underwent TKR at least 2 months prior and
      are otherwise eligible will be randomized into one of three treatment approaches: 1)
      clinic-based individual outpatient rehabilitative exercise; 2) community-based group exercise
      classes; or 3) usual medical care. Subjects will be treated for 3 months. Data will be
      collected before intervention, after intervention (3 months), and 6 months after
      randomization. Physical function is a primary outcome and will be assessed by the Western
      Ontario and McMaster Universities Arthritis Index and a battery of performance-based tests
      germane to patients post TKR that includes ability to walk, manage stairs, lift from the
      floor and the chair, and one-leg balance. We will also use an accelerometer-based monitor
      that provides a real-time measure of physical activity during normal daily living and is able
      to accurately capture most levels of activity. Linear mixed models will be fitted to compare
      the changes in outcome across groups. Logistic regression will identify patient
      characteristics that predict functional recovery in the exercise groups. Survival analysis
      and instrumental variable methods will be used to compare attrition, adherence and adverse
      events between groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF).
time frame: Baseline, 3 and 6 months
description: WOMAC-PF is a patient reported outcome with 17 items. Each item is scored on a 5-point Likert-type Scale with descriptors from 0-4 (none, mild, moderate, severe, and extreme difficulty) and summed for a maximum score of 68. Higher scores indicate worse physical function.
measure: Composite Score of Performed-based Tests of Physical Function.
time frame: Baseline, 3 and 6 months
description: Scores on 6 performance-based tests (i.e., the 6-minute walk test, 40-meter gait speed, stair ascend/descend test, single leg stance balance test, chair stand test, and floor sitting-rising) were combined into a composite score formed with the unit-weighted Z scores of constituent tests to provide a more representative and stable measure of the subjects' underlying functional performance. The unit weights refer to averaging standardized scores (e.g., the scores for each performance-based test are converted to Z-scores before applying equal weights). Higher Z-scores represent better functional performance. The Z-scores for each participant can be interpreted as deviations from the baseline average of the whole group. We considered a change in Z-score of 0.2 as clinically important because it represents approximately 20% of a standard deviation relative to the baseline average of the whole group.
measure: Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear).
time frame: Baseline, 3 and 6 months
description: Real-time measure of daily energy expenditure physical activity assessed by portable activity monitor.
arm group label: Clinic-based outpatient exercise group
arm group type: Experimental
description: Subjects will participate in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session will last about 60 minutes. Treatment sessions will utilize a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.
arm group label: Community-based exercise group
arm group type: Active Comparator
description: Subjects will attend to exercise classes (community-based) 2 times per week during 3 months. The exercise classes last approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.
arm group label: Wait-listed usual medical care
arm group type: No Intervention
description: Wait-listed usual medical care - no intervention provided by study.
intervention type: Other
intervention name: Clinic-based outpatient exercise group
description: Subjects will participate in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session will last about 60 minutes. Treatment sessions will utilize a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.
arm group label: Clinic-based outpatient exercise group
intervention type: Other
intervention name: Community-based exercise group
description: Subjects will attend to exercise classes (community-based) 2 times per week during 3 months. The exercise classes last approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.
arm group label: Community-based exercise group
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Sara R Piva, PT, PhD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Sara R. Piva
investigator title: Dr.
mesh term: Osteoarthritis, Knee
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 