<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/NCT03271151</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0655</org_study_id>
    <nct_id>NCT03271151</nct_id>
  </id_info>
  <brief_title>Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty</brief_title>
  <official_title>Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty: A Double-blinded Randomized Control Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital for Special Surgery, New York</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Post-discharge pain after total knee arthroplasty remains problematic; many patients have&#xD;
      excessive pain at the 2 week time point (and often thereafter). Reduction in opioid use has&#xD;
      become a national goal, due to the 'epidemic' in opioid misuse.&#xD;
&#xD;
      In addition to enrolling non-opioid users, we will enroll up to 15 chronic opioid users.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 28, 2017</start_date>
  <completion_date type="Actual">February 10, 2021</completion_date>
  <primary_completion_date type="Actual">December 3, 2020</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Opioid Use</measure>
    <time_frame>Post-operative day 14</time_frame>
    <description>Opioid use (measured in cumulative morphine equivalents)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain Scores</measure>
    <time_frame>Post-operative day 14</time_frame>
    <description>Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Phenotype</measure>
    <time_frame>Day of surgery</time_frame>
    <description>2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Joint Disease</condition>
  <condition>Pain, Acute</condition>
  <condition>Pain, Chronic</condition>
  <arm_group>
    <arm_group_label>Duloxetine (&quot;Cymbalta&quot;)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo to compare pain scores and opioid use againts Duloxetine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cymbalta</intervention_name>
    <description>Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
    <arm_group_label>Duloxetine (&quot;Cymbalta&quot;)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo to compare outcomes against Duloxetine</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 25 to 75 years&#xD;
&#xD;
          -  Planned use of regional anesthesia&#xD;
&#xD;
          -  Ability to follow study protocol&#xD;
&#xD;
          -  English speaking (Primary outcome obtained via telephone call and secondary outcomes&#xD;
             include questionnaires validated in English only)&#xD;
&#xD;
          -  Patients planning on being discharged home or to a rehabilitation center that has&#xD;
             agreed to participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current Use of duloxetine or other SNRIs, SSRIs, MAOIs, Tricyclic antidepressants,&#xD;
             triptans (sumatriptan, rizatriptan, naratriptan, eletriptan, almotriptan,&#xD;
             frovatriptan), lithium, buspirone, St. John's Wort&#xD;
&#xD;
          -  Hepatic insufficiency&#xD;
&#xD;
             o Hepatoxicity is reported as a side effect of duloxetine. &quot;Median time to detection&#xD;
             of transaminase elevation was about two months&quot; (package insert 5.2&#xD;
&#xD;
          -  Renal insufficiency (ESRD, HD, estimated creatinine clearance &lt; 50 ml/min)&#xD;
&#xD;
               -  Severe CRI may impair duloxetine clearance&#xD;
&#xD;
               -  CLcr=[(140-age (years)] x weight (kg)x0.85 (for female patients)/[72xserum&#xD;
                  creatinine (mg/dL)]&#xD;
&#xD;
          -  Patients younger than 25 years old and older than 75&#xD;
&#xD;
          -  Patients intending to receive general anesthesia&#xD;
&#xD;
          -  Allergy or intolerance to one of the study medications&#xD;
&#xD;
          -  Patients with an ASA of IV&#xD;
&#xD;
          -  Chronic gabapentin/pregabalin use (regular use for longer than 3 months)&#xD;
&#xD;
          -  Patients with major prior ipsilateral open knee surgery.&#xD;
&#xD;
          -  Chronic opioid use (taking opioids for longer than 3 months)&#xD;
&#xD;
               -  However, patients using chronic opioids may enroll in a parallel pilot study&#xD;
                  entitled 'effect of duloxetine on opioid use after total knee athroplasty among&#xD;
                  patients exposed to opioids- a pilot study'. The chronic opioid users will be&#xD;
                  allowed to continue their customary analgesics. The pilot study is otherwise&#xD;
                  identical to the main study.&#xD;
&#xD;
               -  This study will enroll up to 15 chronic opioid users. After that, all chronic&#xD;
                  opioid users are excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jacques T YaDeau, MD, Phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <results_first_submitted>March 29, 2022</results_first_submitted>
  <results_first_submitted_qc>March 29, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 26, 2022</results_first_posted>
  <last_update_submitted>March 29, 2022</last_update_submitted>
  <last_update_submitted_qc>March 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 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>Joint Diseases</mesh_term>
    <mesh_term>Acute Pain</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Duloxetine Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 27, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03271151/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Duloxetine (&quot;Cymbalta&quot;)</title>
          <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.&#xD;
Cymbalta: Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo to compare pain scores and opioid use againts Duloxetine&#xD;
Placebo: Placebo to compare outcomes against Duloxetine</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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>Duloxetine (&quot;Cymbalta&quot;)</title>
          <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.&#xD;
Cymbalta: Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo to compare pain scores and opioid use againts Duloxetine&#xD;
Placebo: Placebo to compare outcomes against Duloxetine</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="80"/>
            <count group_id="B2" value="80"/>
            <count group_id="B3" value="160"/>
          </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="41"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="77"/>
                  </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="63" spread="11"/>
                    <measurement group_id="B2" value="64" spread="7"/>
                    <measurement group_id="B3" value="63" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="154"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Opioid Use</title>
        <description>Opioid use (measured in cumulative morphine equivalents)</description>
        <time_frame>Post-operative day 14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duloxetine (&quot;Cymbalta&quot;)</title>
            <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.&#xD;
Cymbalta: Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo to compare pain scores and opioid use againts Duloxetine&#xD;
Placebo: Placebo to compare outcomes against Duloxetine</description>
          </group>
        </group_list>
        <measure>
          <title>Opioid Use</title>
          <description>Opioid use (measured in cumulative morphine equivalents)</description>
          <units>Oral Morphine Equivalent (mg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="288" spread="226"/>
                    <measurement group_id="O2" value="432.5" spread="374"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pain Scores</title>
        <description>Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.</description>
        <time_frame>Post-operative day 14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duloxetine (&quot;Cymbalta&quot;)</title>
            <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.&#xD;
Cymbalta: Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo to compare pain scores and opioid use againts Duloxetine&#xD;
Placebo: Placebo to compare outcomes against Duloxetine</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Scores</title>
          <description>Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.</description>
          <units>score on a scale (NRS)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="2"/>
                    <measurement group_id="O2" value="4.8" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Phenotype</title>
        <description>2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.</description>
        <time_frame>Day of surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duloxetine (&quot;Cymbalta&quot;)</title>
            <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.&#xD;
Cymbalta: Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo to compare pain scores and opioid use againts Duloxetine&#xD;
Placebo: Placebo to compare outcomes against Duloxetine</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Phenotype</title>
          <description>2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="O2" value="2" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Duloxetine (&quot;Cymbalta&quot;)</title>
          <description>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (&quot;Cymbalta&quot;) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.&#xD;
Cymbalta: Duloxetine (&quot;Cymbalta&quot;) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo to compare pain scores and opioid use againts Duloxetine&#xD;
Placebo: Placebo to compare outcomes against Duloxetine</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="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucinations</sub_title>
                <description>Patient reported experiencing hallucinations. Unclear if related to study medication and/or opioid</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Increased diaphoresis, blood pressure, complaints of diarrhea decreased unration and tooth pain</sub_title>
                <description>Not typical duloxetine side effects; unclear if study related</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <description>Patient reported acne on chest and back, 14 days after surgery. Unclear if due to study</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Unable to Ejaculate</sub_title>
                <description>Unclear if related to study medication and/or opioid medication</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jacques Yadeau</name_or_title>
      <organization>Anesthesiology Critical Care &amp; Pain Management</organization>
      <phone>2127742224</phone>
      <email>Yadeauj@hss.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/NCT03271151
org study id: 2017-0655
nct id: NCT03271151
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Post-discharge pain after total knee arthroplasty remains problematic; many patients have
      excessive pain at the 2 week time point (and often thereafter). Reduction in opioid use has
      become a national goal, due to the 'epidemic' in opioid misuse.

      In addition to enrolling non-opioid users, we will enroll up to 15 chronic opioid users.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Opioid Use
time frame: Post-operative day 14
description: Opioid use (measured in cumulative morphine equivalents)
measure: Pain Scores
time frame: Post-operative day 14
description: Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.
measure: Pain Phenotype
time frame: Day of surgery
description: 2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.
arm group label: Duloxetine ("Cymbalta")
arm group type: Experimental
description: Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine ("Cymbalta") in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo to compare pain scores and opioid use againts Duloxetine
intervention type: Drug
intervention name: Cymbalta
description: Duloxetine ("Cymbalta") is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain
arm group label: Duloxetine ("Cymbalta")
intervention type: Other
intervention name: Placebo
description: Placebo to compare outcomes against Duloxetine
arm group label: Placebo
criteria: 
gender: All
minimum age: 25 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jacques T YaDeau, MD, Phd
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
facility: 
country: United States
responsible party type: Sponsor
mesh term: Joint Diseases
mesh term: Acute Pain
mesh term: Chronic Pain
mesh term: Duloxetine Hydrochloride
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 