<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/NCT03044028</url>
  </required_header>
  <id_info>
    <org_study_id>#16-1293</org_study_id>
    <nct_id>NCT03044028</nct_id>
  </id_info>
  <brief_title>Neuromuscular Electrical Stimulation (NMES) for Improving Outcomes Following Total Knee Arthroplasty (TKA)</brief_title>
  <official_title>Prospective Evaluation of Neuromuscular Electrical Stimulation (NMES) for Improving Outcomes Following Total Knee Arthroplasty (TKA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current standard for rehabilitation after TKA consists of guided exercise therapy for up&#xD;
      to 12 weeks after surgery. This includes inpatient, home, and outpatient therapy. The surgery&#xD;
      and rehabilitation are highly successful at reducing or eliminating pain experienced&#xD;
      preoperatively. However, quadriceps femoris muscle (QFM) strength, overall function, and knee&#xD;
      range of motion are often worse than preoperative levels for as long as 6 months after&#xD;
      surgery and in some cases may persist for many years after that. Such quadriceps strength&#xD;
      impairments after TKA have been largely attributed to voluntary activation deficits and can&#xD;
      lead to a decrease in functional performance such as decreased gait speed, decreased balance&#xD;
      which can lead to falls, and decreased stair climbing &amp; chair rise abilities.&#xD;
&#xD;
      Since therapy alone does not adequately restore or improve upon the preoperative functional&#xD;
      capabilities in a consistent and timely manner, it has been suggested that NMES used&#xD;
      adjunctively with postoperative rehabilitation will alleviate the quadriceps muscle&#xD;
      activation deficits. Early NMES use after TKA has been shown to: reduce knee extensor lag,&#xD;
      increase walking speed, and improve QFM strength, knee range of motion, and function.&#xD;
      However, NMES initiated one month after TKA did not lead to improved QFM strength or function&#xD;
      beyond the standard benefits gained from exercise alone, thus suggesting that the timing of&#xD;
      NMES application after TKA is important.&#xD;
&#xD;
      It has previously been shown that preoperative QFM strength is predictive of postoperative&#xD;
      function [6] but the benefit of prehabilitation remains in question. To date, there has only&#xD;
      been one pilot study assessing the benefits of NMES when initiated preoperatively. This study&#xD;
      only included 14 patients (9 NMES, 5 control) but was able to show that preoperative NMES&#xD;
      usage may lead to greater QFM strength gains after TKA. Therefore, it will be important to&#xD;
      assess the benefits of NMES both preoperatively and postoperatively in order to determine how&#xD;
      it will be most beneficial to TKA patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study duration will be until 12 weeks ± 1 week postoperatively. Data will be collected&#xD;
      (1) 4 weeks preoperatively, (2) prior to hospital admission for TKA, and (3) at 3, 6, and 12&#xD;
      weeks postoperatively. The research coordinator at the site will identify, recruit, and&#xD;
      prospectively follow the 66 patients at his/her site.&#xD;
&#xD;
      All data will be entered and maintained in REDCap, an electronic data capture tools hosted at&#xD;
      Cleveland Clinic. REDCap (Research Electronic Data Capture) is a secure, web-based&#xD;
      application designed to support data capture for research studies, providing 1) an intuitive&#xD;
      interface for validated data entry; 2) audit trails for tracking data manipulation and export&#xD;
      procedures; 3) automated export procedures for seamless data downloads to common statistical&#xD;
      packages; and 4) procedures for importing data from external sources. Only members of the&#xD;
      study team (i.e. the personnel listed on the institutional review board (IRB) application)&#xD;
      will have access to protected health information of patients included in this study.&#xD;
&#xD;
      Pretreatment Assessments&#xD;
&#xD;
      Before treatment, the following assessments/tests will be performed and the results will be&#xD;
      recorded on the appropriate pages of the (case report form) CRF, and or Microsoft excel,&#xD;
      Microsoft Word, and REDCap:&#xD;
&#xD;
        -  Informed consent&#xD;
&#xD;
        -  Age, gender, height/weight/(body mass index) BMI&#xD;
&#xD;
        -  Concomitant diseases&#xD;
&#xD;
        -  Physical examination&#xD;
&#xD;
        -  Baseline range of motion of affected knee&#xD;
&#xD;
        -  Baseline timed up and go test (TUG test, detailed in Appendix A and as described by&#xD;
           Podsiadlo et al.)&#xD;
&#xD;
        -  Baseline Stair Climb test&#xD;
&#xD;
        -  Baseline QFM strength&#xD;
&#xD;
        -  Baseline Modified Knee Injury and Osteoarthritis Outcome Score (KOOS) and Veterans Rand&#xD;
           12(VR-12) assessments&#xD;
&#xD;
        -  Baseline VAS (visual analog scale)pain score&#xD;
&#xD;
        -  Current medications&#xD;
&#xD;
        -  Any use of ambulation assist device&#xD;
&#xD;
      Presurgery Assessments&#xD;
&#xD;
      Before surgery, the following assessments/tests will be performed and the results will be&#xD;
      recorded on the appropriate pages of the CRF, and or Microsoft excel, Microsoft Word, and&#xD;
      REDCap:&#xD;
&#xD;
        -  Device usage patterns (thru app for preop NMES group)&#xD;
&#xD;
        -  Range of motion of affected knee&#xD;
&#xD;
        -  TUG test&#xD;
&#xD;
        -  Stair Climb test&#xD;
&#xD;
        -  QFM strength&#xD;
&#xD;
        -  Modified KOOS and VR-12 assessments&#xD;
&#xD;
        -  VAS pain score&#xD;
&#xD;
        -  Current medications&#xD;
&#xD;
        -  Activity levels using Misfit Wearables® fitness monitor will be uploaded and&#xD;
           incorporated into online app&#xD;
&#xD;
      Operative Assessments&#xD;
&#xD;
      The following will be collected from the Operative and Anesthesia Records and recorded on the&#xD;
      appropriate pages of the CRF, and or Microsoft excel, Microsoft Word, and REDCap:&#xD;
&#xD;
        -  Surgeon name&#xD;
&#xD;
        -  Approach used&#xD;
&#xD;
        -  Randomization assignment&#xD;
&#xD;
        -  Diagnosis&#xD;
&#xD;
        -  Length of surgery&#xD;
&#xD;
        -  Estimated blood loss&#xD;
&#xD;
        -  Type of anesthesia&#xD;
&#xD;
        -  Implant type&#xD;
&#xD;
      Postoperative Assessments After surgery, one or more of the following will be collected&#xD;
      through the online app and at follow-up visits.&#xD;
&#xD;
        -  Device usage patterns (thru app)&#xD;
&#xD;
        -  Range of motion of affected knee (thru app and at follow-up)&#xD;
&#xD;
        -  TUG test&#xD;
&#xD;
        -  Stair Climb test&#xD;
&#xD;
        -  QFM strength&#xD;
&#xD;
        -  Modified KOOS and VR-12 assessments&#xD;
&#xD;
        -  VAS pain score&#xD;
&#xD;
        -  Length of stay (hospital, extended care facility)&#xD;
&#xD;
        -  90 day readmission rate&#xD;
&#xD;
        -  Discharge Disposition (home vs skilled nursing facility vs inpatient rehabilitation)&#xD;
&#xD;
        -  Patient Satisfaction measures&#xD;
&#xD;
        -  Any use of an ambulation assist aid&#xD;
&#xD;
        -  Activity levels using Misfit Wearables® fitness monitor will be uploaded and&#xD;
           incorporated into online app&#xD;
&#xD;
      As a last resort, if a patient is unable to keep one of these appointments, he/she will be&#xD;
      either be mailed or emailed the patient reported outcome forms so the patient can fill them&#xD;
      out. The patient will date and time the forms. Participants will then send the form back in a&#xD;
      pre-addressed envelope. The patients email will be verified by the patient during a clinical&#xD;
      visit to ensure accuracy of the correct recipient. Patients not responding to the initial&#xD;
      mailer will be contacted by phone and forms may be administered over the phone. The mailers&#xD;
      and/or phone calls will allow us to collect all data except the physical function measures.&#xD;
&#xD;
      All data will be entered and maintained in Redcap&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quadriceps Femoris Muscle (QFM) Strength (Dynamometer Quad Strength Lbs)</measure>
    <time_frame>6 weeks</time_frame>
    <description>measure change in muscle strength (QFM) - difference from baseline measure to 6 weeks postoperative</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Knee Active Range of Motion (Extension, Flexion) in Degrees</measure>
    <time_frame>12 weeks</time_frame>
    <description>Measure rage of motion differences between the treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Analogue Scale (VAS) Pain Level (0-10 Scale)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Differences in VAS scores between the treatment groups from baseline to 12 weeks postop. Higher score represents worse pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Length of Stay (Days)</measure>
    <time_frame>12 weeks</time_frame>
    <description>differences in length of stay between the treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Discharged to Extended Care Facility</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patent discharge other than &quot;home&quot; to extended care facility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Readmitted to Hospital</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of all-cause readmissions to the hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Outpatient Therapy Visits (Patient Questionnaire)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Difference in number of outpatient therapy visits among the treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KOOS - PS</measure>
    <time_frame>12 weeks</time_frame>
    <description>Functional outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS) Physical Function Shortform (PS) questionnaire. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KOOS Pain</measure>
    <time_frame>12 weeks</time_frame>
    <description>Measure pain at 12 weeks postoperative using Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscore. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Arthropathy of Knee Joint</condition>
  <arm_group>
    <arm_group_label>NMES preoperative and postoperative</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use preoperative and will continue to use postoperatively until end of study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NMES postoperative only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use postoperatively and will continue to use until end of study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No intervention</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subject will not be given device and will undergo the standard rehab protocol alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CyMedica Orthopedics QB1 e-vive™ system</intervention_name>
    <description>a multifunctional electrotherapy device providing neuromuscular electrical stimulation (NMES), for improving quadriceps strength and improving functional outcomes accelerating functional recovery in patients managed with total knee arthroplasty (TKA).</description>
    <arm_group_label>NMES postoperative only</arm_group_label>
    <arm_group_label>NMES preoperative and postoperative</arm_group_label>
    <other_name>NMES Neuromuscular electrical stimulation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients undergoing unilateral primary total knee arthroplasty&#xD;
&#xD;
          2. Patients who are between the ages of 18 - 85 years&#xD;
&#xD;
          3. Patient has signed informed consent&#xD;
&#xD;
          4. Patient has access to a smartphone or tablet (Android or iOS)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. BMI ≥ 40&#xD;
&#xD;
          2. Inflammatory arthritis&#xD;
&#xD;
          3. Patients who are expected to be in extended care facilities after surgery&#xD;
&#xD;
          4. Patients who have used an at-home NMES device in the past&#xD;
&#xD;
          5. Preoperative daily use of narcotics (i.e., high tolerance)&#xD;
&#xD;
          6. Already enrolled in another research study, including the present study for&#xD;
             contralateral knee&#xD;
&#xD;
          7. Other lower-extremity orthopaedic conditions which could interfere with limb function,&#xD;
             especially those with significant pain requiring daily analgesic intake&#xD;
&#xD;
          8. Patients with concurrent abdominal, inguinal or femoral hernias&#xD;
&#xD;
          9. Cutaneous lesions in areas of electrode pad placement&#xD;
&#xD;
         10. Patients with a history of epilepsy&#xD;
&#xD;
         11. Patients with a cardiac pacemaker/defibrillator&#xD;
&#xD;
         12. Allergy to adhesives&#xD;
&#xD;
         13. Inability to meet follow-up visits required for the study&#xD;
&#xD;
         14. Patients who are a risk for poor compliance or have a poor understanding of the use of&#xD;
             the NMES device&#xD;
&#xD;
         15. Condition deemed by physician or medical staff to be non-conducive to patient's&#xD;
             ability to complete the study, or a potential risk to the patient's health and&#xD;
             well-being&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Mont</last_name>
    <role>Study Chair</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Stevens-Lapsley JE, Balter JE, Wolfe P, Eckhoff DG, Kohrt WM. Early neuromuscular electrical stimulation to improve quadriceps muscle strength after total knee arthroplasty: a randomized controlled trial. Phys Ther. 2012 Feb;92(2):210-26. doi: 10.2522/ptj.20110124. Epub 2011 Nov 17.</citation>
    <PMID>22095207</PMID>
  </reference>
  <reference>
    <citation>Levine M, McElroy K, Stakich V, Cicco J. Comparing conventional physical therapy rehabilitation with neuromuscular electrical stimulation after TKA. Orthopedics. 2013 Mar;36(3):e319-24. doi: 10.3928/01477447-20130222-20.</citation>
    <PMID>23464951</PMID>
  </reference>
  <reference>
    <citation>Gotlin RS, Hershkowitz S, Juris PM, Gonzalez EG, Scott WN, Insall JN. Electrical stimulation effect on extensor lag and length of hospital stay after total knee arthroplasty. Arch Phys Med Rehabil. 1994 Sep;75(9):957-9.</citation>
    <PMID>8085929</PMID>
  </reference>
  <reference>
    <citation>Avramidis K, Karachalios T, Popotonasios K, Sacorafas D, Papathanasiades AA, Malizos KN. Does electric stimulation of the vastus medialis muscle influence rehabilitation after total knee replacement? Orthopedics. 2011 Mar 11;34(3):175. doi: 10.3928/01477447-20110124-06.</citation>
    <PMID>21410130</PMID>
  </reference>
  <reference>
    <citation>Petterson SC, Mizner RL, Stevens JE, Raisis L, Bodenstab A, Newcomb W, Snyder-Mackler L. Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with an imbedded prospective cohort. Arthritis Rheum. 2009 Feb 15;61(2):174-83. doi: 10.1002/art.24167.</citation>
    <PMID>19177542</PMID>
  </reference>
  <reference>
    <citation>Mizner RL, Petterson SC, Stevens JE, Axe MJ, Snyder-Mackler L. Preoperative quadriceps strength predicts functional ability one year after total knee arthroplasty. J Rheumatol. 2005 Aug;32(8):1533-9.</citation>
    <PMID>16078331</PMID>
  </reference>
  <reference>
    <citation>D'Lima DD, Colwell CW Jr, Morris BA, Hardwick ME, Kozin F. The effect of preoperative exercise on total knee replacement outcomes. Clin Orthop Relat Res. 1996 May;(326):174-82. doi: 10.1097/00003086-199605000-00020.</citation>
    <PMID>8620638</PMID>
  </reference>
  <reference>
    <citation>Villadsen A. Neuromuscular exercise prior to joint arthroplasty in patients with osteoarthritis of the hip or knee. Dan Med J. 2016 Apr;63(4):B5235. No abstract available.</citation>
    <PMID>27034190</PMID>
  </reference>
  <reference>
    <citation>Rodgers JA, Garvin KL, Walker CW, Morford D, Urban J, Bedard J. Preoperative physical therapy in primary total knee arthroplasty. J Arthroplasty. 1998 Jun;13(4):414-21. doi: 10.1016/s0883-5403(98)90007-9.</citation>
    <PMID>9645522</PMID>
  </reference>
  <reference>
    <citation>Walls RJ, McHugh G, O'Gorman DJ, Moyna NM, O'Byrne JM. Effects of preoperative neuromuscular electrical stimulation on quadriceps strength and functional recovery in total knee arthroplasty. A pilot study. BMC Musculoskelet Disord. 2010 Jun 14;11:119. doi: 10.1186/1471-2474-11-119.</citation>
    <PMID>20540807</PMID>
  </reference>
  <reference>
    <citation>Klika AK, Gehrig M, Boukis L, Milidonis MK, Smith DA, Murray TG, Barsoum WK. A Rapid Recovery Program After Total Knee Arthroplasty. Semin Arthro. 2009; 20:40-44.</citation>
  </reference>
  <reference>
    <citation>Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998 Aug;28(2):88-96. doi: 10.2519/jospt.1998.28.2.88.</citation>
    <PMID>9699158</PMID>
  </reference>
  <reference>
    <citation>Brazier JE, Roberts J. The estimation of a preference-based measure of health from the SF-12. Med Care. 2004 Sep;42(9):851-9. doi: 10.1097/01.mlr.0000135827.18610.0d.</citation>
    <PMID>15319610</PMID>
  </reference>
  <reference>
    <citation>Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1983 Sep;17(1):45-56. doi: 10.1016/0304-3959(83)90126-4.</citation>
    <PMID>6226917</PMID>
  </reference>
  <reference>
    <citation>Podsiadlo D, Richardson S. The timed &quot;Up &amp; Go&quot;: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.</citation>
    <PMID>1991946</PMID>
  </reference>
  <reference>
    <citation>Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.</citation>
    <PMID>18929686</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <results_first_submitted>September 27, 2019</results_first_submitted>
  <results_first_submitted_qc>February 21, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 5, 2020</results_first_posted>
  <last_update_submitted>February 21, 2020</last_update_submitted>
  <last_update_submitted_qc>February 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Carlos Higuera-Rueda</investigator_full_name>
    <investigator_title>Staff Surgeon</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Diseases</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>January 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03044028/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NMES Preoperative and Postoperative</title>
          <description>Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use preoperative and will continue to use postoperatively until end of study&#xD;
CyMedica Orthopedics QB1 e-vive™ system: a multifunctional electrotherapy device providing neuromuscular electrical stimulation (NMES), for improving quadriceps strength and improving functional outcomes accelerating functional recovery in patients managed with total knee arthroplasty (TKA).</description>
        </group>
        <group group_id="P2">
          <title>NMES Postoperative Only</title>
          <description>Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use postoperatively and will continue to use until end of study&#xD;
CyMedica Orthopedics QB1 e-vive™ system: a multifunctional electrotherapy device providing neuromuscular electrical stimulation (NMES), for improving quadriceps strength and improving functional outcomes accelerating functional recovery in patients managed with total knee arthroplasty (TKA).</description>
        </group>
        <group group_id="P3">
          <title>No Intervention</title>
          <description>Subject will not be given device and will undergo the standard rehab protocol alone</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NMES Preoperative and Postoperative</title>
          <description>Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use preoperative and will continue to use postoperatively until end of study&#xD;
CyMedica Orthopedics QB1 e-vive™ system: a multifunctional electrotherapy device providing neuromuscular electrical stimulation (NMES), for improving quadriceps strength and improving functional outcomes accelerating functional recovery in patients managed with total knee arthroplasty (TKA).</description>
        </group>
        <group group_id="B2">
          <title>NMES Postoperative Only</title>
          <description>Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use postoperatively and will continue to use until end of study&#xD;
CyMedica Orthopedics QB1 e-vive™ system: a multifunctional electrotherapy device providing neuromuscular electrical stimulation (NMES), for improving quadriceps strength and improving functional outcomes accelerating functional recovery in patients managed with total knee arthroplasty (TKA).</description>
        </group>
        <group group_id="B3">
          <title>No Intervention</title>
          <description>Subject will not be given device and will undergo the standard rehab protocol alone</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="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="22"/>
            <count group_id="B4" value="46"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="22"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.0" spread="5.2"/>
                    <measurement group_id="B2" value="66.6" spread="6.3"/>
                    <measurement group_id="B3" value="64.5" spread="7.6"/>
                    <measurement group_id="B4" value="64.9" spread="6.7"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="22"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Race not collected</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="22"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Quadriceps Femoris Muscle (QFM) Strength (Dynamometer Quad Strength Lbs)</title>
        <description>measure change in muscle strength (QFM) - difference from baseline measure to 6 weeks postoperative</description>
        <time_frame>6 weeks</time_frame>
        <population>Numbers do not match Participant Flow because data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Quadriceps Femoris Muscle (QFM) Strength (Dynamometer Quad Strength Lbs)</title>
          <description>measure change in muscle strength (QFM) - difference from baseline measure to 6 weeks postoperative</description>
          <population>Numbers do not match Participant Flow because data were missing.</population>
          <units>lbs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.35" spread="20.70"/>
                    <measurement group_id="O2" value="15.95" spread="14.61"/>
                    <measurement group_id="O3" value="-5.48" spread="16.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Knee Active Range of Motion (Extension, Flexion) in Degrees</title>
        <description>Measure rage of motion differences between the treatment groups</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Knee Active Range of Motion (Extension, Flexion) in Degrees</title>
          <description>Measure rage of motion differences between the treatment groups</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.50" spread="13.22"/>
                    <measurement group_id="O2" value="6.67" spread="15.40"/>
                    <measurement group_id="O3" value="-1.50" spread="12.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Visual Analogue Scale (VAS) Pain Level (0-10 Scale)</title>
        <description>Differences in VAS scores between the treatment groups from baseline to 12 weeks postop. Higher score represents worse pain.</description>
        <time_frame>12 weeks</time_frame>
        <population>Numbers do not match Participant Flow because data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Analogue Scale (VAS) Pain Level (0-10 Scale)</title>
          <description>Differences in VAS scores between the treatment groups from baseline to 12 weeks postop. Higher score represents worse pain.</description>
          <population>Numbers do not match Participant Flow because data were missing.</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="12"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" spread="2.92"/>
                    <measurement group_id="O2" value="1.80" spread="2.04"/>
                    <measurement group_id="O3" value="1.18" spread="2.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital Length of Stay (Days)</title>
        <description>differences in length of stay between the treatment groups</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital Length of Stay (Days)</title>
          <description>differences in length of stay between the treatment groups</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.83" spread="0.72"/>
                    <measurement group_id="O2" value="1.75" spread="0.45"/>
                    <measurement group_id="O3" value="1.68" spread="0.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Discharged to Extended Care Facility</title>
        <description>Patent discharge other than &quot;home&quot; to extended care facility</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Discharged to Extended Care Facility</title>
          <description>Patent discharge other than &quot;home&quot; to extended care facility</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Readmitted to Hospital</title>
        <description>Number of all-cause readmissions to the hospital</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Readmitted to Hospital</title>
          <description>Number of all-cause readmissions to the hospital</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Outpatient Therapy Visits (Patient Questionnaire)</title>
        <description>Difference in number of outpatient therapy visits among the treatment groups</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Outpatient Therapy Visits (Patient Questionnaire)</title>
          <description>Difference in number of outpatient therapy visits among the treatment groups</description>
          <units>visits</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.86" spread="4.95"/>
                    <measurement group_id="O2" value="16.25" spread="7.29"/>
                    <measurement group_id="O3" value="11.67" spread="5.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>KOOS - PS</title>
        <description>Functional outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS) Physical Function Shortform (PS) questionnaire. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.</description>
        <time_frame>12 weeks</time_frame>
        <population>Numbers do not match Participant Flow because data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>KOOS - PS</title>
          <description>Functional outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS) Physical Function Shortform (PS) questionnaire. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.</description>
          <population>Numbers do not match Participant Flow because data were missing.</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="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.43" spread="14.76"/>
                    <measurement group_id="O2" value="20.39" spread="12.70"/>
                    <measurement group_id="O3" value="26.62" spread="9.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>KOOS Pain</title>
        <description>Measure pain at 12 weeks postoperative using Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscore. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.</description>
        <time_frame>12 weeks</time_frame>
        <population>Numbers do not match Participant Flow because data were missing.</population>
        <group_list>
          <group group_id="O1">
            <title>NMES Preoperative and Postoperative</title>
            <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
          </group>
          <group group_id="O2">
            <title>NMES Postoperative Only</title>
            <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
          </group>
          <group group_id="O3">
            <title>Control - no NMES</title>
            <description>Control - no NMES, patients did not use the device</description>
          </group>
        </group_list>
        <measure>
          <title>KOOS Pain</title>
          <description>Measure pain at 12 weeks postoperative using Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscore. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.</description>
          <population>Numbers do not match Participant Flow because data were missing.</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="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.22" spread="19.64"/>
                    <measurement group_id="O2" value="78.89" spread="16.57"/>
                    <measurement group_id="O3" value="80.38" spread="15.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected through 12 weeks postoperative.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>NMES Preoperative and Postoperative</title>
          <description>NMES Preoperative and Postoperative, patients used the device a minimum of 900 minutes total preoperatively, and 200 min/wk postoperatively</description>
        </group>
        <group group_id="E2">
          <title>NMES Postoperative Only</title>
          <description>NMES Postoperative only, patients used the device a minimum of 200 min/wk postoperatively</description>
        </group>
        <group group_id="E3">
          <title>Control - no NMES</title>
          <description>Control - no NMES, patients did not use the device</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Readmission</sub_title>
                <description>Patient was having abdominal pain and was admitted to hospital. Problem unrelated to study and resolved.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </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>Carlos Higuera</name_or_title>
      <organization>Cleveland Clinic</organization>
      <phone>954-659-5430</phone>
      <email>higuerc@ccf.org</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/NCT03044028
org study id: #16-1293
nct id: NCT03044028
lead sponsor: 
has dmc: Yes
The current standard for rehabilitation after TKA consists of guided exercise therapy for up
      to 12 weeks after surgery. This includes inpatient, home, and outpatient therapy. The surgery
      and rehabilitation are highly successful at reducing or eliminating pain experienced
      preoperatively. However, quadriceps femoris muscle (QFM) strength, overall function, and knee
      range of motion are often worse than preoperative levels for as long as 6 months after
      surgery and in some cases may persist for many years after that. Such quadriceps strength
      impairments after TKA have been largely attributed to voluntary activation deficits and can
      lead to a decrease in functional performance such as decreased gait speed, decreased balance
      which can lead to falls, and decreased stair climbing & chair rise abilities.

      Since therapy alone does not adequately restore or improve upon the preoperative functional
      capabilities in a consistent and timely manner, it has been suggested that NMES used
      adjunctively with postoperative rehabilitation will alleviate the quadriceps muscle
      activation deficits. Early NMES use after TKA has been shown to: reduce knee extensor lag,
      increase walking speed, and improve QFM strength, knee range of motion, and function.
      However, NMES initiated one month after TKA did not lead to improved QFM strength or function
      beyond the standard benefits gained from exercise alone, thus suggesting that the timing of
      NMES application after TKA is important.

      It has previously been shown that preoperative QFM strength is predictive of postoperative
      function [6] but the benefit of prehabilitation remains in question. To date, there has only
      been one pilot study assessing the benefits of NMES when initiated preoperatively. This study
      only included 14 patients (9 NMES, 5 control) but was able to show that preoperative NMES
      usage may lead to greater QFM strength gains after TKA. Therefore, it will be important to
      assess the benefits of NMES both preoperatively and postoperatively in order to determine how
      it will be most beneficial to TKA patients.
The study duration will be until 12 weeks ± 1 week postoperatively. Data will be collected
      (1) 4 weeks preoperatively, (2) prior to hospital admission for TKA, and (3) at 3, 6, and 12
      weeks postoperatively. The research coordinator at the site will identify, recruit, and
      prospectively follow the 66 patients at his/her site.

      All data will be entered and maintained in REDCap, an electronic data capture tools hosted at
      Cleveland Clinic. REDCap (Research Electronic Data Capture) is a secure, web-based
      application designed to support data capture for research studies, providing 1) an intuitive
      interface for validated data entry; 2) audit trails for tracking data manipulation and export
      procedures; 3) automated export procedures for seamless data downloads to common statistical
      packages; and 4) procedures for importing data from external sources. Only members of the
      study team (i.e. the personnel listed on the institutional review board (IRB) application)
      will have access to protected health information of patients included in this study.

      Pretreatment Assessments

      Before treatment, the following assessments/tests will be performed and the results will be
      recorded on the appropriate pages of the (case report form) CRF, and or Microsoft excel,
      Microsoft Word, and REDCap:

        -  Informed consent

        -  Age, gender, height/weight/(body mass index) BMI

        -  Concomitant diseases

        -  Physical examination

        -  Baseline range of motion of affected knee

        -  Baseline timed up and go test (TUG test, detailed in Appendix A and as described by
           Podsiadlo et al.)

        -  Baseline Stair Climb test

        -  Baseline QFM strength

        -  Baseline Modified Knee Injury and Osteoarthritis Outcome Score (KOOS) and Veterans Rand
           12(VR-12) assessments

        -  Baseline VAS (visual analog scale)pain score

        -  Current medications

        -  Any use of ambulation assist device

      Presurgery Assessments

      Before surgery, the following assessments/tests will be performed and the results will be
      recorded on the appropriate pages of the CRF, and or Microsoft excel, Microsoft Word, and
      REDCap:

        -  Device usage patterns (thru app for preop NMES group)

        -  Range of motion of affected knee

        -  TUG test

        -  Stair Climb test

        -  QFM strength

        -  Modified KOOS and VR-12 assessments

        -  VAS pain score

        -  Current medications

        -  Activity levels using Misfit Wearables® fitness monitor will be uploaded and
           incorporated into online app

      Operative Assessments

      The following will be collected from the Operative and Anesthesia Records and recorded on the
      appropriate pages of the CRF, and or Microsoft excel, Microsoft Word, and REDCap:

        -  Surgeon name

        -  Approach used

        -  Randomization assignment

        -  Diagnosis

        -  Length of surgery

        -  Estimated blood loss

        -  Type of anesthesia

        -  Implant type

      Postoperative Assessments After surgery, one or more of the following will be collected
      through the online app and at follow-up visits.

        -  Device usage patterns (thru app)

        -  Range of motion of affected knee (thru app and at follow-up)

        -  TUG test

        -  Stair Climb test

        -  QFM strength

        -  Modified KOOS and VR-12 assessments

        -  VAS pain score

        -  Length of stay (hospital, extended care facility)

        -  90 day readmission rate

        -  Discharge Disposition (home vs skilled nursing facility vs inpatient rehabilitation)

        -  Patient Satisfaction measures

        -  Any use of an ambulation assist aid

        -  Activity levels using Misfit Wearables® fitness monitor will be uploaded and
           incorporated into online app

      As a last resort, if a patient is unable to keep one of these appointments, he/she will be
      either be mailed or emailed the patient reported outcome forms so the patient can fill them
      out. The patient will date and time the forms. Participants will then send the form back in a
      pre-addressed envelope. The patients email will be verified by the patient during a clinical
      visit to ensure accuracy of the correct recipient. Patients not responding to the initial
      mailer will be contacted by phone and forms may be administered over the phone. The mailers
      and/or phone calls will allow us to collect all data except the physical function measures.

      All data will be entered and maintained in Redcap
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Quadriceps Femoris Muscle (QFM) Strength (Dynamometer Quad Strength Lbs)
time frame: 6 weeks
description: measure change in muscle strength (QFM) - difference from baseline measure to 6 weeks postoperative
measure: Knee Active Range of Motion (Extension, Flexion) in Degrees
time frame: 12 weeks
description: Measure rage of motion differences between the treatment groups
measure: Visual Analogue Scale (VAS) Pain Level (0-10 Scale)
time frame: 12 weeks
description: Differences in VAS scores between the treatment groups from baseline to 12 weeks postop. Higher score represents worse pain.
measure: Hospital Length of Stay (Days)
time frame: 12 weeks
description: differences in length of stay between the treatment groups
measure: Number of Patients Discharged to Extended Care Facility
time frame: 12 weeks
description: Patent discharge other than "home" to extended care facility
measure: Number of Patients Readmitted to Hospital
time frame: 12 weeks
description: Number of all-cause readmissions to the hospital
measure: Number of Outpatient Therapy Visits (Patient Questionnaire)
time frame: 12 weeks
description: Difference in number of outpatient therapy visits among the treatment groups
measure: KOOS - PS
time frame: 12 weeks
description: Functional outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS) Physical Function Shortform (PS) questionnaire. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.
measure: KOOS Pain
time frame: 12 weeks
description: Measure pain at 12 weeks postoperative using Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscore. Change in total score from baseline to 12 weeks postoperative score. Minimum value is 0, maximum value is 100, and higher values mean greater improvement over baseline total score.
arm group label: NMES preoperative and postoperative
arm group type: Experimental
description: Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use preoperative and will continue to use postoperatively until end of study
arm group label: NMES postoperative only
arm group type: Experimental
description: Subject will be given NMES CyMedica Orthopedics QB1 e-vive™ system device to use postoperatively and will continue to use until end of study
arm group label: No intervention
arm group type: No Intervention
description: Subject will not be given device and will undergo the standard rehab protocol alone
intervention type: Device
intervention name: CyMedica Orthopedics QB1 e-vive™ system
description: a multifunctional electrotherapy device providing neuromuscular electrical stimulation (NMES), for improving quadriceps strength and improving functional outcomes accelerating functional recovery in patients managed with total knee arthroplasty (TKA).
arm group label: NMES postoperative only
arm group label: NMES preoperative and postoperative
other name: NMES Neuromuscular electrical stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Michael Mont
role: Study Chair
affiliation: The Cleveland Clinic
facility: 
country: United States
citation: Stevens-Lapsley JE, Balter JE, Wolfe P, Eckhoff DG, Kohrt WM. Early neuromuscular electrical stimulation to improve quadriceps muscle strength after total knee arthroplasty: a randomized controlled trial. Phys Ther. 2012 Feb;92(2):210-26. doi: 10.2522/ptj.20110124. Epub 2011 Nov 17.
PMID: 22095207
citation: Levine M, McElroy K, Stakich V, Cicco J. Comparing conventional physical therapy rehabilitation with neuromuscular electrical stimulation after TKA. Orthopedics. 2013 Mar;36(3):e319-24. doi: 10.3928/01477447-20130222-20.
PMID: 23464951
citation: Gotlin RS, Hershkowitz S, Juris PM, Gonzalez EG, Scott WN, Insall JN. Electrical stimulation effect on extensor lag and length of hospital stay after total knee arthroplasty. Arch Phys Med Rehabil. 1994 Sep;75(9):957-9.
PMID: 8085929
citation: Avramidis K, Karachalios T, Popotonasios K, Sacorafas D, Papathanasiades AA, Malizos KN. Does electric stimulation of the vastus medialis muscle influence rehabilitation after total knee replacement? Orthopedics. 2011 Mar 11;34(3):175. doi: 10.3928/01477447-20110124-06.
PMID: 21410130
citation: Petterson SC, Mizner RL, Stevens JE, Raisis L, Bodenstab A, Newcomb W, Snyder-Mackler L. Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with an imbedded prospective cohort. Arthritis Rheum. 2009 Feb 15;61(2):174-83. doi: 10.1002/art.24167.
PMID: 19177542
citation: Mizner RL, Petterson SC, Stevens JE, Axe MJ, Snyder-Mackler L. Preoperative quadriceps strength predicts functional ability one year after total knee arthroplasty. J Rheumatol. 2005 Aug;32(8):1533-9.
PMID: 16078331
citation: D'Lima DD, Colwell CW Jr, Morris BA, Hardwick ME, Kozin F. The effect of preoperative exercise on total knee replacement outcomes. Clin Orthop Relat Res. 1996 May;(326):174-82. doi: 10.1097/00003086-199605000-00020.
PMID: 8620638
citation: Villadsen A. Neuromuscular exercise prior to joint arthroplasty in patients with osteoarthritis of the hip or knee. Dan Med J. 2016 Apr;63(4):B5235. No abstract available.
PMID: 27034190
citation: Rodgers JA, Garvin KL, Walker CW, Morford D, Urban J, Bedard J. Preoperative physical therapy in primary total knee arthroplasty. J Arthroplasty. 1998 Jun;13(4):414-21. doi: 10.1016/s0883-5403(98)90007-9.
PMID: 9645522
citation: Walls RJ, McHugh G, O'Gorman DJ, Moyna NM, O'Byrne JM. Effects of preoperative neuromuscular electrical stimulation on quadriceps strength and functional recovery in total knee arthroplasty. A pilot study. BMC Musculoskelet Disord. 2010 Jun 14;11:119. doi: 10.1186/1471-2474-11-119.
PMID: 20540807
citation: Klika AK, Gehrig M, Boukis L, Milidonis MK, Smith DA, Murray TG, Barsoum WK. A Rapid Recovery Program After Total Knee Arthroplasty. Semin Arthro. 2009; 20:40-44.
citation: Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998 Aug;28(2):88-96. doi: 10.2519/jospt.1998.28.2.88.
PMID: 9699158
citation: Brazier JE, Roberts J. The estimation of a preference-based measure of health from the SF-12. Med Care. 2004 Sep;42(9):851-9. doi: 10.1097/01.mlr.0000135827.18610.0d.
PMID: 15319610
citation: Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1983 Sep;17(1):45-56. doi: 10.1016/0304-3959(83)90126-4.
PMID: 6226917
citation: Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.
PMID: 1991946
citation: Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.
PMID: 18929686
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Carlos Higuera-Rueda
investigator title: Staff Surgeon
mesh term: Joint Diseases
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 