<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/NCT03001453</url>
  </required_header>
  <id_info>
    <org_study_id>AHI-001</org_study_id>
    <nct_id>NCT03001453</nct_id>
  </id_info>
  <brief_title>Intraoperative Liposomal Bupivacaine vs. Bupivacaine for Total Hip Replacement Pain Management</brief_title>
  <official_title>Post-surgical Pain Care Pathways During Enhanced Recovery Surgery Using Exparel (Bupivacaine Liposome Injectable Suspension) Plus Bupivacaine With Epinephrine Versus Bupivacaine.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>American Hip Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>American Hip Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare two medications currently injected intra-operatively&#xD;
      to help decrease pain after surgery in patients undergoing a primary total hip replacement&#xD;
      (THR). The two medications are Exparel® (bupivacaine liposome injectable suspension) plus&#xD;
      bupivacaine with epinephrine versus bupivacaine with epinephrine. This study is looking to&#xD;
      see if one medication works better than the other in managing post-operative pain after THR.&#xD;
      The study hypothesis is that Exparel® plus bupivacaine with epinephrine will demonstrate&#xD;
      better pain management in THR patients post-operatively. Both medications are FDA-approved&#xD;
      for post-operative analgesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All surgeries were performed by the same orthopaedic surgeon. Two groups, one receiving&#xD;
      Exparel® (bupivacaine liposome injectable suspension) plus bupivacaine with epinephrine (LB&#xD;
      group) and the other receiving bupivacaine with epinephrine (Control group), will be compared&#xD;
      using post-operative pain scores, hospital length of stay, time to ambulation, falls,&#xD;
      narcotic use, and narcotic-related adverse effects. Aside from hospital length of stay, all&#xD;
      outcomes were recorded for up to 72 hours following surgery. An a priori power analysis was&#xD;
      performed to calculate the total number of patients that needed to be enrolled to achieve a&#xD;
      minimum 90% power, with the threshold of statistical significance set to 0.05. Based on a&#xD;
      previous study reporting a mean oral opioid consumption of 57.04mg ± 25.6 at 24 hours post&#xD;
      THR, a mean difference of 17.14mg was considered to be clinically significant. Thus, at least&#xD;
      26 patients were necessary in each group for an adequately powered assessment. The diagnosis&#xD;
      for osteoarthritis was determined by patient history, physical examination, and imaging&#xD;
      findings. Each patient received a thorough explanation of the protocol, and willing patients&#xD;
      signed an informed consent form. All patients underwent a personal preoperative education&#xD;
      program regarding pre, intra-, and post-procedural information including physical therapy,&#xD;
      expectations, discharge goals, home therapy, and pain management. After written consent was&#xD;
      collected, the form was sent to the hospital pharmacy for randomization. Envelopes were&#xD;
      randomized, sealed, numbered, and given to the pharmacy staff, ultimately dispensing the&#xD;
      envelopes to the nurse in the operating room in numerical order. The pharmacy documented the&#xD;
      required information, selected medication, and drug accountability forms according to the&#xD;
      contents of the envelopes.&#xD;
&#xD;
      A nurse delivered study drugs to the operating room in a sealed, non-descriptive envelope.&#xD;
      During the standard anterior approach procedure, an anesthesiologist administered fentanyl or&#xD;
      hydromorphone as needed for analgesia. The local anesthetics were administered after&#xD;
      reduction of the implants. Patients in the LB group received 20cc liposomal bupivacaine, 40cc&#xD;
      0.25% bupivacaine with epinephrine, and 20cc of normal saline. Each patient in the control&#xD;
      group received 60cc of 0.25% bupivacaine with epinephrine. Using a 20-gauge spinal needle,&#xD;
      the local anesthetics were injected using a deep tissue administration technique. Structures&#xD;
      innervated by the femoral nerve, superior gluteal nerve, or lateral femoral cutaneous nerve&#xD;
      were considered suitable for injection. Throughout administration, frequent aspirations were&#xD;
      performed to check for blood and minimize the risk of intravascular injection. The patients,&#xD;
      surgical team, and floor staff was blinded to the local anesthetic drugs given.&#xD;
&#xD;
      During hospitalization, patients were observed, evaluated and treated according to&#xD;
      postoperative protocols. Patients received opioids for pain management as needed, which was&#xD;
      routinely documented by hospital staff. Opioids included fentanyl, hydromorphone, oxycodone,&#xD;
      codeine, tramadol, morphine, and hydrocodone. All opioid dosages were converted into morphine&#xD;
      equivalent dosages for analysis. Each patient began physical therapy within the first 24&#xD;
      hours postoperatively. Patients were discharged when they were able to begin self-care, their&#xD;
      pain was controlled utilizing an oral regimen, and they were able to tolerate oral medication&#xD;
      intake.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>Patient Morphine Equivalent Consumption</measure>
    <time_frame>72 hours postoperation, divided into six 12-hour periods</time_frame>
    <description>All opioid doses were administered to the patient at 12-hour intervals post-surgery. Doses were recorded till either of the following criteria was met, the patient was discharged or the 72-hour post-surgery timeframe ended. The doses were then collected and converted to OMEs, in milligrams.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Patient-reported Visual Analog Scale (VAS) Pain Intensity Score</measure>
    <time_frame>72 hours post-operation, divided into six 12-hour periods</time_frame>
    <description>Patient-reported VAS pain intensity score (0 = no pain, 10 = worst pain possible) will be collected. Mean VAS scores for the 72-hour period were calculated using the cohort's reported average pain scores at each 12-hour interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Ambulation More Than 20 Feet (in Hours)</measure>
    <time_frame>from time of surgery until patient first ambulates more than 20 feet or 72 hours post-surgery or patient discharge, whichever comes first</time_frame>
    <description>The length of time (in hours) until the patient first ambulates more than 20 feet from the time of surgery will be recorded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Length of Stay (LOS, in Days)</measure>
    <time_frame>From time of surgery until patient is discharged, an average of 1.5 days.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients That Experienced a Fall</measure>
    <time_frame>72 hours postoperation</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Liposomal bupivacaine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bupivacaine with epinephrine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal Bupivacaine</intervention_name>
    <description>266mg liposomal bupivacaine</description>
    <arm_group_label>Liposomal bupivacaine</arm_group_label>
    <other_name>Exparel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.25% Bupivacaine with epinephrine</intervention_name>
    <description>0.25% bupivacaine with epinephrine</description>
    <arm_group_label>Bupivacaine with epinephrine</arm_group_label>
    <arm_group_label>Liposomal bupivacaine</arm_group_label>
    <other_name>Marcaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Normal saline</description>
    <arm_group_label>Liposomal bupivacaine</arm_group_label>
    <other_name>Saline solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients scheduled to undergo primary unilateral total hip replacement&#xD;
&#xD;
          -  Patients diagnosed with hip osteoarthritis&#xD;
&#xD;
          -  Patients failed to improve with conservative measures&#xD;
&#xD;
          -  Patients willing and able to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Revision total hip replacement&#xD;
&#xD;
          -  Bilateral total hip replacement&#xD;
&#xD;
          -  Birmingham hip resurfacing&#xD;
&#xD;
          -  Patients with hepatic/kidney disease&#xD;
&#xD;
          -  Patients with a known allergy to bupivacaine or other local anesthetics&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benjamin G Domb, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>American Hip Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Adventist Hinsdale Hospital</name>
      <address>
        <city>Hinsdale</city>
        <state>Illinois</state>
        <zip>60521</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Hip Institute</name>
      <address>
        <city>Westmont</city>
        <state>Illinois</state>
        <zip>60559</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>November 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <results_first_submitted>January 3, 2018</results_first_submitted>
  <results_first_submitted_qc>June 28, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">July 26, 2018</results_first_posted>
  <last_update_submitted>June 28, 2018</last_update_submitted>
  <last_update_submitted_qc>June 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>American Hip Institute</investigator_affiliation>
    <investigator_full_name>Benjamin Domb</investigator_full_name>
    <investigator_title>Medical Director</investigator_title>
  </responsible_party>
  <keyword>Exparel</keyword>
  <keyword>total hip replacement</keyword>
  <keyword>bupivacaine</keyword>
  <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>Epinephrine</mesh_term>
    <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>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
        </group>
        <group group_id="P2">
          <title>Bupivacaine With Epinephrine</title>
          <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</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="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Liposomal Bupivacaine</title>
          <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
        </group>
        <group group_id="B2">
          <title>Bupivacaine With Epinephrine</title>
          <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</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="50"/>
            <count group_id="B2" value="57"/>
            <count group_id="B3" value="107"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.9" lower_limit="41.8" upper_limit="80"/>
                    <measurement group_id="B2" value="62.4" lower_limit="33.7" upper_limit="82.1"/>
                    <measurement group_id="B3" value="62.1" lower_limit="33.7" upper_limit="82.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.2" lower_limit="18.6" upper_limit="46"/>
                    <measurement group_id="B2" value="31" lower_limit="19.5" upper_limit="55.4"/>
                    <measurement group_id="B3" value="30.1" lower_limit="18.6" upper_limit="55.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Laterality</title>
          <units>hips</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Left</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Right</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Robotic assistance</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Preoperative opioid prescription</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Codeine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hydrocodone</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hydromorphine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oxycodone</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>American Society of Anesthesiologists Grade</title>
          <description>Patients were graded based on the American Society of Anesthesiologists Physical Status Classification System. 1 indicates a normal healthy patient, 2 is a patient with a mild systemic disease, 3 is a patient with a severe systemic disease, and 4 is a patient with a severe systemic disease that is a constant threat to life. Grade 1 is considered to be a better outcome while Grade 4 is considered to be a worse outcome.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Exercise regularly</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Patient Morphine Equivalent Consumption</title>
        <description>All opioid doses were administered to the patient at 12-hour intervals post-surgery. Doses were recorded till either of the following criteria was met, the patient was discharged or the 72-hour post-surgery timeframe ended. The doses were then collected and converted to OMEs, in milligrams.</description>
        <time_frame>72 hours postoperation, divided into six 12-hour periods</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine With Epinephrine</title>
            <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Morphine Equivalent Consumption</title>
          <description>All opioid doses were administered to the patient at 12-hour intervals post-surgery. Doses were recorded till either of the following criteria was met, the patient was discharged or the 72-hour post-surgery timeframe ended. The doses were then collected and converted to OMEs, in milligrams.</description>
          <units>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="50"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0-12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.1" spread="24.4"/>
                    <measurement group_id="O2" value="50.5" spread="34.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12-24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.0" spread="17.4"/>
                    <measurement group_id="O2" value="29.6" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24-36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.8" spread="14.9"/>
                    <measurement group_id="O2" value="21.0" spread="20.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>36-48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.6" spread="17.0"/>
                    <measurement group_id="O2" value="27.4" spread="21.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48-60</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.7" spread="19.5"/>
                    <measurement group_id="O2" value="15.4" spread="19.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-72</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.9" spread="19.6"/>
                    <measurement group_id="O2" value="20.7" spread="13.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.3" spread="74.3"/>
                    <measurement group_id="O2" value="121.2" spread="87.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Patient-reported Visual Analog Scale (VAS) Pain Intensity Score</title>
        <description>Patient-reported VAS pain intensity score (0 = no pain, 10 = worst pain possible) will be collected. Mean VAS scores for the 72-hour period were calculated using the cohort's reported average pain scores at each 12-hour interval.</description>
        <time_frame>72 hours post-operation, divided into six 12-hour periods</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine With Epinephrine</title>
            <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Patient-reported Visual Analog Scale (VAS) Pain Intensity Score</title>
          <description>Patient-reported VAS pain intensity score (0 = no pain, 10 = worst pain possible) will be collected. Mean VAS scores for the 72-hour period were calculated using the cohort's reported average pain scores at each 12-hour interval.</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="50"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="1.6"/>
                    <measurement group_id="O2" value="3.7" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Ambulation More Than 20 Feet (in Hours)</title>
        <description>The length of time (in hours) until the patient first ambulates more than 20 feet from the time of surgery will be recorded.</description>
        <time_frame>from time of surgery until patient first ambulates more than 20 feet or 72 hours post-surgery or patient discharge, whichever comes first</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine With Epinephrine</title>
            <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Ambulation More Than 20 Feet (in Hours)</title>
          <description>The length of time (in hours) until the patient first ambulates more than 20 feet from the time of surgery will be recorded.</description>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.9" spread="8.8"/>
                    <measurement group_id="O2" value="14.0" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Length of Stay (LOS, in Days)</title>
        <time_frame>From time of surgery until patient is discharged, an average of 1.5 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine With Epinephrine</title>
            <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay (LOS, in Days)</title>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0" spread="26.2"/>
                    <measurement group_id="O2" value="44.4" spread="27.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients That Experienced a Fall</title>
        <time_frame>72 hours postoperation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liposomal Bupivacaine</title>
            <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
          </group>
          <group group_id="O2">
            <title>Bupivacaine With Epinephrine</title>
            <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Experienced a Fall</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Liposomal Bupivacaine</title>
          <description>Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine&#xD;
Liposomal Bupivacaine: 266mg liposomal bupivacaine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine&#xD;
Saline: Normal saline</description>
        </group>
        <group group_id="E2">
          <title>Bupivacaine With Epinephrine</title>
          <description>Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine&#xD;
0.25% Bupivacaine with epinephrine: 0.25% bupivacaine with epinephrine</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="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </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="14" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Benjamin Domb</name_or_title>
      <organization>American Hip Institute</organization>
      <phone>630-455-7130</phone>
      <email>drdomb@americanhipinstitute.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03001453
org study id: AHI-001
nct id: NCT03001453
lead sponsor: 
has dmc: No
The purpose of this study is to compare two medications currently injected intra-operatively
      to help decrease pain after surgery in patients undergoing a primary total hip replacement
      (THR). The two medications are Exparel® (bupivacaine liposome injectable suspension) plus
      bupivacaine with epinephrine versus bupivacaine with epinephrine. This study is looking to
      see if one medication works better than the other in managing post-operative pain after THR.
      The study hypothesis is that Exparel® plus bupivacaine with epinephrine will demonstrate
      better pain management in THR patients post-operatively. Both medications are FDA-approved
      for post-operative analgesia.
All surgeries were performed by the same orthopaedic surgeon. Two groups, one receiving
      Exparel® (bupivacaine liposome injectable suspension) plus bupivacaine with epinephrine (LB
      group) and the other receiving bupivacaine with epinephrine (Control group), will be compared
      using post-operative pain scores, hospital length of stay, time to ambulation, falls,
      narcotic use, and narcotic-related adverse effects. Aside from hospital length of stay, all
      outcomes were recorded for up to 72 hours following surgery. An a priori power analysis was
      performed to calculate the total number of patients that needed to be enrolled to achieve a
      minimum 90% power, with the threshold of statistical significance set to 0.05. Based on a
      previous study reporting a mean oral opioid consumption of 57.04mg ± 25.6 at 24 hours post
      THR, a mean difference of 17.14mg was considered to be clinically significant. Thus, at least
      26 patients were necessary in each group for an adequately powered assessment. The diagnosis
      for osteoarthritis was determined by patient history, physical examination, and imaging
      findings. Each patient received a thorough explanation of the protocol, and willing patients
      signed an informed consent form. All patients underwent a personal preoperative education
      program regarding pre, intra-, and post-procedural information including physical therapy,
      expectations, discharge goals, home therapy, and pain management. After written consent was
      collected, the form was sent to the hospital pharmacy for randomization. Envelopes were
      randomized, sealed, numbered, and given to the pharmacy staff, ultimately dispensing the
      envelopes to the nurse in the operating room in numerical order. The pharmacy documented the
      required information, selected medication, and drug accountability forms according to the
      contents of the envelopes.

      A nurse delivered study drugs to the operating room in a sealed, non-descriptive envelope.
      During the standard anterior approach procedure, an anesthesiologist administered fentanyl or
      hydromorphone as needed for analgesia. The local anesthetics were administered after
      reduction of the implants. Patients in the LB group received 20cc liposomal bupivacaine, 40cc
      0.25% bupivacaine with epinephrine, and 20cc of normal saline. Each patient in the control
      group received 60cc of 0.25% bupivacaine with epinephrine. Using a 20-gauge spinal needle,
      the local anesthetics were injected using a deep tissue administration technique. Structures
      innervated by the femoral nerve, superior gluteal nerve, or lateral femoral cutaneous nerve
      were considered suitable for injection. Throughout administration, frequent aspirations were
      performed to check for blood and minimize the risk of intravascular injection. The patients,
      surgical team, and floor staff was blinded to the local anesthetic drugs given.

      During hospitalization, patients were observed, evaluated and treated according to
      postoperative protocols. Patients received opioids for pain management as needed, which was
      routinely documented by hospital staff. Opioids included fentanyl, hydromorphone, oxycodone,
      codeine, tramadol, morphine, and hydrocodone. All opioid dosages were converted into morphine
      equivalent dosages for analysis. Each patient began physical therapy within the first 24
      hours postoperatively. Patients were discharged when they were able to begin self-care, their
      pain was controlled utilizing an oral regimen, and they were able to tolerate oral medication
      intake.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Patient Morphine Equivalent Consumption
time frame: 72 hours postoperation, divided into six 12-hour periods
description: All opioid doses were administered to the patient at 12-hour intervals post-surgery. Doses were recorded till either of the following criteria was met, the patient was discharged or the 72-hour post-surgery timeframe ended. The doses were then collected and converted to OMEs, in milligrams.
measure: Change in Patient-reported Visual Analog Scale (VAS) Pain Intensity Score
time frame: 72 hours post-operation, divided into six 12-hour periods
description: Patient-reported VAS pain intensity score (0 = no pain, 10 = worst pain possible) will be collected. Mean VAS scores for the 72-hour period were calculated using the cohort's reported average pain scores at each 12-hour interval.
measure: Time to Ambulation More Than 20 Feet (in Hours)
time frame: from time of surgery until patient first ambulates more than 20 feet or 72 hours post-surgery or patient discharge, whichever comes first
description: The length of time (in hours) until the patient first ambulates more than 20 feet from the time of surgery will be recorded.
measure: Length of Stay (LOS, in Days)
time frame: From time of surgery until patient is discharged, an average of 1.5 days.
measure: Number of Patients That Experienced a Fall
time frame: 72 hours postoperation
arm group label: Liposomal bupivacaine
arm group type: Active Comparator
description: Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine
arm group label: Bupivacaine with epinephrine
arm group type: Active Comparator
description: Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine
intervention type: Drug
intervention name: Liposomal Bupivacaine
description: 266mg liposomal bupivacaine
arm group label: Liposomal bupivacaine
other name: Exparel
intervention type: Drug
intervention name: 0.25% Bupivacaine with epinephrine
description: 0.25% bupivacaine with epinephrine
arm group label: Bupivacaine with epinephrine
arm group label: Liposomal bupivacaine
other name: Marcaine
intervention type: Drug
intervention name: Saline
description: Normal saline
arm group label: Liposomal bupivacaine
other name: Saline solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Benjamin G Domb, MD
role: Principal Investigator
affiliation: American Hip Institute
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: American Hip Institute
investigator full name: Benjamin Domb
investigator title: Medical Director
mesh term: Pain, Postoperative
mesh term: Epinephrine
mesh term: Bupivacaine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 