<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/NCT03011307</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00036246</org_study_id>
    <nct_id>NCT03011307</nct_id>
  </id_info>
  <brief_title>Efficacy of Intrathecal Oxytocin to Speed Recovery After Hip Surgery</brief_title>
  <official_title>Efficacy of Intrathecal Oxytocin to Speed Recovery After Hip Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the effect of intrathecal oxytocin on speed of&#xD;
      reduction in pain for the first 60 days after hip surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, NIH funded clinical study at Wake Forest Baptist Medical Center. The&#xD;
      investigators anticipate that intrathecal oxytocin will speed recovery from pain after major&#xD;
      surgery (hip arthroplasty). For this study, the investigators will use a randomized,&#xD;
      controlled and blinded study of intrathecal oxytocin in patients scheduled for hip&#xD;
      arthroplasty, with primary outcome being the slope of change in pain over the first 60 days&#xD;
      following surgery, using growth curve modeling and a ln(time) function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Cessation of funding period prior to completion, due to slow recruitment during the pandemic.&#xD;
  </why_stopped>
  <start_date type="Actual">January 12, 2017</start_date>
  <completion_date type="Actual">August 11, 2021</completion_date>
  <primary_completion_date type="Actual">October 23, 2020</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept</measure>
    <time_frame>The first day after hospital discharge</time_frame>
    <description>Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.&#xD;
Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope</measure>
    <time_frame>Postoperative Day 1 through Postoperative Day 60</time_frame>
    <description>Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.&#xD;
Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept</measure>
    <time_frame>The first day after hospital discharge</time_frame>
    <description>Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol.&#xD;
Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope</measure>
    <time_frame>Postoperative Day 1 through Postoperative Day 60</time_frame>
    <description>Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept</measure>
    <time_frame>Modeled WHODAS 2.0 one week after hospital discharge</time_frame>
    <description>Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.&#xD;
Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope</measure>
    <time_frame>Postoperative Day 7 through Postoperative Day 56</time_frame>
    <description>Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.&#xD;
Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept</measure>
    <time_frame>The first day after hospital discharge</time_frame>
    <description>Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.&#xD;
Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope</measure>
    <time_frame>Postoperative Day 1 through Postoperative Day 60</time_frame>
    <description>Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.&#xD;
Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iowa Gambling Task</measure>
    <time_frame>Preoperative, 2 months after surgery</time_frame>
    <description>This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wisconsin Card Sort Task</measure>
    <time_frame>Preoperative, 2 months after surgery</time_frame>
    <description>This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tampa Scale of Kinesiophobia</measure>
    <time_frame>Preoperative, 2 months after surgery</time_frame>
    <description>This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Postoperative Pain</condition>
  <arm_group>
    <arm_group_label>Oxytocin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oxytocin 100 micrograms administered intrathecally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo injection administered intrathecally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>spinal injection of oxytocin</description>
    <arm_group_label>Oxytocin</arm_group_label>
    <other_name>Pitocin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>spinal injection of placebo</description>
    <arm_group_label>Placebos</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Scheduled for unilateral, primary total hip replacement&#xD;
&#xD;
          -  American Society of Anesthesiologists physical status 1-3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Currently Workman's Comp litigation related to hip replacement&#xD;
&#xD;
          -  Taking greater than 100 milligrams of morphine (or equivalent)&#xD;
&#xD;
          -  Suffering from a psychotic disorder or a recent psychiatric hospitalization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James C Eisenach, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wake Forest Baptist Medical Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <results_first_submitted>August 1, 2022</results_first_submitted>
  <results_first_submitted_qc>November 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 23, 2022</results_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 13, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03011307/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 3, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03011307/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 30, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03011307/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment occurred from January 12, 2017 to August 3, 2020 at the Orthopeadic Clinics of Atrium Wake Forest Baptist and Davie County facilities.</recruitment_details>
      <pre_assignment_details>Enrollment occurred greater or equal to 2 weeks prior to surgery. A total of 28 individuals were excluded prior to assignment to groups during the period prior to surgery because of withdrawal of consent (n=25) or cancellation of the planned surgery (n=3).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Oxytocin</title>
          <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="46"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Did not receive study drug: blood pressure or heart rate instability before spinal injection</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive study drug: unable to place spinal needle</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive study drug: unable to obtain study drug from formulating pharmacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Oxytocin</title>
          <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="44"/>
            <count group_id="B2" value="46"/>
            <count group_id="B3" value="90"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" spread="8.7"/>
                    <measurement group_id="B2" value="59" spread="10"/>
                    <measurement group_id="B3" value="61" spread="9.5"/>
                  </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="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="38"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="90"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="83"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Worst daily pain</title>
          <description>From daily diaries completed for 2 weeks prior to surgery in which the participant rated each day the worst pain in the past 24 hours with 0=no pain and 10=worst 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="5.0" spread="2.9"/>
                    <measurement group_id="B2" value="5.8" spread="2.3"/>
                    <measurement group_id="B3" value="5.4" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Daily steps</title>
          <description>Steps each day for 2 weeks prior to surgery as measured with an activity monitor</description>
          <units>Steps per day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6440" spread="4120"/>
                    <measurement group_id="B2" value="6918" spread="4613"/>
                    <measurement group_id="B3" value="6672" spread="4511"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disability</title>
          <description>Preoperative measure of disability on the World Health Organization Disability Assessment Scale 2.0 where no disability = 12 and severe disability =36</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="20.8" spread="6.1"/>
                    <measurement group_id="B2" value="21.6" spread="5.0"/>
                    <measurement group_id="B3" value="21.2" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept</title>
        <description>Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.&#xD;
Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
        <time_frame>The first day after hospital discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept</title>
          <description>Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.&#xD;
Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
          <units>score on a scale</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" lower_limit="5.8" upper_limit="11.2"/>
                    <measurement group_id="O2" value="8.6" lower_limit="5.9" upper_limit="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.75</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Intercept Difference in score on a scale</param_type>
            <param_value>0.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope</title>
        <description>Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.&#xD;
Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
        <time_frame>Postoperative Day 1 through Postoperative Day 60</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope</title>
          <description>Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.&#xD;
Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
          <units>Score on a scale</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" lower_limit="-2.2" upper_limit="-1.6"/>
                    <measurement group_id="O2" value="-2" lower_limit="-2.3" upper_limit="-1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.057</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope Difference</param_type>
            <param_value>0.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0</ci_lower_limit>
            <ci_upper_limit>0.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept</title>
        <description>Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol.&#xD;
Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
        <time_frame>The first day after hospital discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept</title>
          <description>Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol.&#xD;
Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
          <units>Daily Steps</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="144" lower_limit="-2436" upper_limit="3527"/>
                    <measurement group_id="O2" value="546" lower_limit="-3241" upper_limit="4332"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.41</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Intercept Difference in Daily Steps</param_type>
            <param_value>-402</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1358</ci_lower_limit>
            <ci_upper_limit>553</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope</title>
        <description>Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
        <time_frame>Postoperative Day 1 through Postoperative Day 60</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope</title>
          <description>Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
          <units>Daily steps</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="562" lower_limit="-130" upper_limit="1248"/>
                    <measurement group_id="O2" value="218" lower_limit="-472" upper_limit="907"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.&#xD;
The slope is the number of daily steps divided by the natural log of time in days.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Slope Difference</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>344</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>173</ci_lower_limit>
            <ci_upper_limit>515</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept</title>
        <description>Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.&#xD;
Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
        <time_frame>Modeled WHODAS 2.0 one week after hospital discharge</time_frame>
        <population>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept</title>
          <description>Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.&#xD;
Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
          <population>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</population>
          <units>score on a scale</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.2" lower_limit="9.5" upper_limit="41.2"/>
                    <measurement group_id="O2" value="29.1" lower_limit="13.5" upper_limit="44.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in World Health Organization Disability Assessment Score 2.0 value was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.002</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Intercept Difference: score on a scale</param_type>
            <param_value>-5.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.5</ci_lower_limit>
            <ci_upper_limit>-2.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope</title>
        <description>Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.&#xD;
Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
        <time_frame>Postoperative Day 7 through Postoperative Day 56</time_frame>
        <population>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</population>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope</title>
          <description>Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.&#xD;
Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.</description>
          <population>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</population>
          <units>Score on a scale/ln(days)</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.1" lower_limit="-11" upper_limit="-3.2"/>
                    <measurement group_id="O2" value="-5.6" lower_limit="-9.5" upper_limit="-1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.001</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope Difference</param_type>
            <param_value>1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>2.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept</title>
        <description>Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.&#xD;
Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model.</description>
        <time_frame>The first day after hospital discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept</title>
          <description>Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.&#xD;
Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model.</description>
          <units>Probability of taking opioids</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9995" lower_limit="0.9985" upper_limit="1.0005"/>
                    <measurement group_id="O2" value="0.9998" lower_limit="0.9989" upper_limit="1.0007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.537</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Intercept difference: Opioid probability</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.00035</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-.00085</ci_lower_limit>
            <ci_upper_limit>.0015</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope</title>
        <description>Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.&#xD;
Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model</description>
        <time_frame>Postoperative Day 1 through Postoperative Day 60</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope</title>
          <description>Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.&#xD;
Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model</description>
          <units>Probability of taking opioids/ln(days)</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.953" lower_limit="-0.959" upper_limit="-0.947"/>
                    <measurement group_id="O2" value="-0.787" lower_limit="-0.799" upper_limit="-0.775"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without oxytocin treatment group. A statistically significant result is interpreted as evidence to support that the oxytocin treatment impacts some element of change after surgery (i.e, intercept or slope).</non_inferiority_desc>
            <p_value>0.010</p_value>
            <p_value_desc>P value not adjusted for multiple comparisons, with threshold of statistical significance set at &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope Difference: Opioid probability</param_type>
            <param_value>-0.166</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.172</ci_lower_limit>
            <ci_upper_limit>-0.160</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Iowa Gambling Task</title>
        <description>This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity</description>
        <time_frame>Preoperative, 2 months after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Iowa Gambling Task</title>
          <description>This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13" spread="30"/>
                    <measurement group_id="O2" value="21" spread="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 Months postoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20" spread="38"/>
                    <measurement group_id="O2" value="22" spread="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Scores were compared statistically at baseline and 2 months between groups using a generalized linear model with time as a fixed factor.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.55</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>3</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>14</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Wisconsin Card Sort Task</title>
        <description>This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.</description>
        <time_frame>Preoperative, 2 months after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Wisconsin Card Sort Task</title>
          <description>This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="4.2"/>
                    <measurement group_id="O2" value="6.8" spread="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 Months postoperatively</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.4" spread="4.2"/>
                    <measurement group_id="O2" value="7.7" spread="6.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Groups were compared over time from baseline to 2 months using a generalized linear model with time as a fixed factor.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.46</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.2</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>2.2</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tampa Scale of Kinesiophobia</title>
        <description>This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.</description>
        <time_frame>Preoperative, 2 months after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oxytocin</title>
            <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Tampa Scale of Kinesiophobia</title>
          <description>This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37" spread="4.8"/>
                    <measurement group_id="O2" value="38" spread="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 month postoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36" spread="3.8"/>
                    <measurement group_id="O2" value="36" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Groups were compared between preoperative and 2 month postoperative sessions using linear regression with time as a fixed factor.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.38</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.24</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.84</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Deaths and Serious adverse events were evaluated from baseline through month 6. Non-serious adverse events were evaluated from baseline through month 2.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oxytocin</title>
          <description>Oxytocin 100 micrograms administered intrathecally&#xD;
Oxytocin: spinal injection of oxytocin</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo injection administered intrathecally&#xD;
Placebos: spinal injection of placebo</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="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="46"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="46"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="46"/>
              </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>
    <limitations_and_caveats>The trial was terminated early because of depletion of funding. Power analysis was based on 120 subjects and only 90 were studied before termination of funding .</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. James Eisenach</name_or_title>
      <organization>Wake Forest University School of Medicine</organization>
      <phone>336-716-4182</phone>
      <email>eisenach@wakehealth.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03011307
org study id: IRB00036246
nct id: NCT03011307
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the effect of intrathecal oxytocin on speed of
      reduction in pain for the first 60 days after hip surgery.
This is a single-center, NIH funded clinical study at Wake Forest Baptist Medical Center. The
      investigators anticipate that intrathecal oxytocin will speed recovery from pain after major
      surgery (hip arthroplasty). For this study, the investigators will use a randomized,
      controlled and blinded study of intrathecal oxytocin in patients scheduled for hip
      arthroplasty, with primary outcome being the slope of change in pain over the first 60 days
      following surgery, using growth curve modeling and a ln(time) function.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept
time frame: The first day after hospital discharge
description: Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.
Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
measure: Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope
time frame: Postoperative Day 1 through Postoperative Day 60
description: Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.
Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
measure: Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept
time frame: The first day after hospital discharge
description: Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol.
Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
measure: Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope
time frame: Postoperative Day 1 through Postoperative Day 60
description: Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
measure: Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept
time frame: Modeled WHODAS 2.0 one week after hospital discharge
description: Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.
Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
measure: Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope
time frame: Postoperative Day 7 through Postoperative Day 56
description: Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability.
Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
measure: Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept
time frame: The first day after hospital discharge
description: Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.
Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model.
measure: Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope
time frame: Postoperative Day 1 through Postoperative Day 60
description: Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately.
Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model
measure: Iowa Gambling Task
time frame: Preoperative, 2 months after surgery
description: This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity
measure: Wisconsin Card Sort Task
time frame: Preoperative, 2 months after surgery
description: This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.
measure: Tampa Scale of Kinesiophobia
time frame: Preoperative, 2 months after surgery
description: This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.
arm group label: Oxytocin
arm group type: Experimental
description: Oxytocin 100 micrograms administered intrathecally
arm group label: Placebos
arm group type: Placebo Comparator
description: Placebo injection administered intrathecally
intervention type: Drug
intervention name: Oxytocin
description: spinal injection of oxytocin
arm group label: Oxytocin
other name: Pitocin
intervention type: Drug
intervention name: Placebo
description: spinal injection of placebo
arm group label: Placebos
other name: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: James C Eisenach, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Oxytocin
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The trial was terminated early because of depletion of funding. Power analysis was based on 120 subjects and only 90 were studied before termination of funding .
point of contact: 