<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/NCT02219087</url>
  </required_header>
  <id_info>
    <org_study_id>14-0024</org_study_id>
    <nct_id>NCT02219087</nct_id>
  </id_info>
  <brief_title>Liposomal Bupivacaine Versus Standard of Care in Total Knee Surgery</brief_title>
  <official_title>Local Liposomal Bupivacaine Versus Standard of Care in an Opioid-Sparing Analgesic Approach to Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OhioHealth</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>OhioHealth</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether liposomal bupivacaine is effective in the&#xD;
      management of pain following total knee arthroplasty, as compared to standard of care&#xD;
      analgesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Liposomal bupivacaine (Exparel®) is a local anesthetic made up of liposomal encapsulated&#xD;
      bupivacaine. It is designed to be injected at the time of surgery into the local soft&#xD;
      tissues. Because of its unique liposomal delivery system, Liposomal bupivacaine (Exparel®)&#xD;
      has been shown to provide up to 96 hours of pain relief following surgeries. This makes it an&#xD;
      attractive option in total knee arthroplasty patients. Combined with the proven efficacy of&#xD;
      regional anesthesia, intraoperative liposomal bupivacaine (Exparel®) may provide extended&#xD;
      pain relief following total knee arthroplasty. This has the potential to avoid the need for&#xD;
      opioid medications. With better pain control, medication side effects can be avoided and&#xD;
      patient's length of stay in the hospital can be shortened.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number Physical Therapy Sessions Necessary for Discharge</measure>
    <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
    <description>Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay</measure>
    <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
    <description>VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay (LOS, in Days)</measure>
    <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams)</measure>
    <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay</measure>
    <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
    <description>Nausea&#xD;
Vomiting&#xD;
Constipation&#xD;
Ileus&#xD;
Pruritus&#xD;
Respiratory depression&#xD;
Over-sedation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Cost of Care (Dollars)</measure>
    <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Readmission Not Including Admissions Planned Procedures</measure>
    <time_frame>Participants will be followed for 30 days after leaving the hospital.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>Liposomal Bupivacaine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal bupivacaine</intervention_name>
    <arm_group_label>Liposomal Bupivacaine</arm_group_label>
    <other_name>Exparel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
          -  Scheduled to undergo total knee arthroplasty (TKA) performed by the principal&#xD;
             investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 years&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Non-English-speaking&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  Patients admitted from or discharged to a medical facility (due to likelihood of&#xD;
             limited mobility and/or required minimum lengths of stay, confounding primary&#xD;
             outcome), including other hospitals, skilled nursing facilities, long-term acute care&#xD;
             hospitals, etc.&#xD;
&#xD;
          -  Patients unable to complete a device-assisted 140 foot walk at baseline&#xD;
&#xD;
          -  Patients with contraindication(s) to any bupivacaine or ropivacaine formulation, to&#xD;
             nerve blocks or any of the local agents used (IV morphine, ketorolac, or&#xD;
             methylprednisolone).&#xD;
&#xD;
          -  Patients on a long-acting maintenance opioid prior to admission for surgery (e.g.,&#xD;
             methadone, oxycontin)&#xD;
&#xD;
          -  Patients undergoing simultaneous bilateral TKAs, as this would increase the dose of&#xD;
             Exparel per patient (we are limited to one dose per patient)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert Fada, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OhioHealth</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sara Jordan, PharmD, BCPS</last_name>
    <role>Study Director</role>
    <affiliation>OhioHealth</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OhioHealth Grant Medical Center Bone and Joint Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <results_first_submitted>October 14, 2016</results_first_submitted>
  <results_first_submitted_qc>December 1, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">January 2, 2018</results_first_posted>
  <last_update_submitted>December 1, 2017</last_update_submitted>
  <last_update_submitted_qc>December 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OhioHealth</investigator_affiliation>
    <investigator_full_name>Robert Fada, MD</investigator_full_name>
    <investigator_title>Orthopedic Surgeon</investigator_title>
  </responsible_party>
  <keyword>Total knee arthroplasty</keyword>
  <keyword>Total joint arthroplasty</keyword>
  <keyword>Knee replacement</keyword>
  <keyword>Osteoarthritis of the knee</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Liposomal Bupivacaine</title>
          <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care</title>
          <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="29">Randomization envelope pulled out of sequence for consented patient. Excluded by request of IRB</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Randomization envelope pulled out of seq</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Liposomal Bupivacaine</title>
          <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care</title>
          <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</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="30"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="59"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.0" spread="8.3"/>
                    <measurement group_id="B2" value="61.2" spread="8.9"/>
                    <measurement group_id="B3" value="63.1" spread="8.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number Physical Therapy Sessions Necessary for Discharge</title>
        <description>Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission.</description>
        <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Number Physical Therapy Sessions Necessary for Discharge</title>
          <description>Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission.</description>
          <units>Physical Therapy Sessions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="1.2"/>
                    <measurement group_id="O2" value="3.6" spread="1.3"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.137</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay</title>
        <description>VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated</description>
        <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay</title>
          <description>VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated</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="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="1.3"/>
                    <measurement group_id="O2" value="4.7" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.343</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay (LOS, in Days)</title>
        <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay (LOS, in Days)</title>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="0.8"/>
                    <measurement group_id="O2" value="2.3" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.208</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams)</title>
        <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams)</title>
          <units>Milligrams</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="274.6" spread="121.0"/>
                    <measurement group_id="O2" value="304.8" spread="143.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.385</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay</title>
        <description>Nausea&#xD;
Vomiting&#xD;
Constipation&#xD;
Ileus&#xD;
Pruritus&#xD;
Respiratory depression&#xD;
Over-sedation</description>
        <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay</title>
          <description>Nausea&#xD;
Vomiting&#xD;
Constipation&#xD;
Ileus&#xD;
Pruritus&#xD;
Respiratory depression&#xD;
Over-sedation</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.843</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Cost of Care (Dollars)</title>
        <time_frame>Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Total Cost of Care (Dollars)</title>
          <units>Dollars</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64582.90" lower_limit="55424.50" upper_limit="121583.50"/>
                    <measurement group_id="O2" value="62601.50" lower_limit="52435.90" upper_limit="97367.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.438</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital Readmission Not Including Admissions Planned Procedures</title>
        <time_frame>Participants will be followed for 30 days after leaving the hospital.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital Readmission Not Including Admissions Planned Procedures</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Liposomal Bupivacaine</title>
          <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.&#xD;
Liposomal bupivacaine</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care</title>
          <description>Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.&#xD;
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Oversedation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </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>Sara Jordan Clinical Pharmacist for Surgery Services</name_or_title>
      <organization>OhioHealth</organization>
      <phone>614-461-8174</phone>
      <email>sara.jordan@ohiohealth.com</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/NCT02219087
org study id: 14-0024
nct id: NCT02219087
lead sponsor: 
has dmc: No
The purpose of this study is to determine whether liposomal bupivacaine is effective in the
      management of pain following total knee arthroplasty, as compared to standard of care
      analgesia.
Liposomal bupivacaine (Exparel®) is a local anesthetic made up of liposomal encapsulated
      bupivacaine. It is designed to be injected at the time of surgery into the local soft
      tissues. Because of its unique liposomal delivery system, Liposomal bupivacaine (Exparel®)
      has been shown to provide up to 96 hours of pain relief following surgeries. This makes it an
      attractive option in total knee arthroplasty patients. Combined with the proven efficacy of
      regional anesthesia, intraoperative liposomal bupivacaine (Exparel®) may provide extended
      pain relief following total knee arthroplasty. This has the potential to avoid the need for
      opioid medications. With better pain control, medication side effects can be avoided and
      patient's length of stay in the hospital can be shortened.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Number Physical Therapy Sessions Necessary for Discharge
time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
description: Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission.
measure: Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay
time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
description: VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated
measure: Length of Stay (LOS, in Days)
time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
measure: Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams)
time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
measure: Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay
time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
description: Nausea
Vomiting
Constipation
Ileus
Pruritus
Respiratory depression
Over-sedation
measure: Total Cost of Care (Dollars)
time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
measure: Hospital Readmission Not Including Admissions Planned Procedures
time frame: Participants will be followed for 30 days after leaving the hospital.
arm group label: Liposomal Bupivacaine
arm group type: Experimental
description: Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.
arm group label: Standard of Care
arm group type: Active Comparator
description: Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.
intervention type: Drug
intervention name: Liposomal bupivacaine
arm group label: Liposomal Bupivacaine
other name: Exparel
intervention type: Drug
intervention name: Standard of Care
description: Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert Fada, MD
role: Principal Investigator
affiliation: OhioHealth
last name: Sara Jordan, PharmD, BCPS
role: Study Director
affiliation: OhioHealth
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OhioHealth
investigator full name: Robert Fada, MD
investigator title: Orthopedic Surgeon
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Bupivacaine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 