<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/NCT03305666</url>
  </required_header>
  <id_info>
    <org_study_id>17-0685</org_study_id>
    <nct_id>NCT03305666</nct_id>
  </id_info>
  <brief_title>Trial of Injected Liposomal Bupivacaine vs Bupivacaine Infusion After Surgical Stabilization of Rib Fractures</brief_title>
  <official_title>A Randomized Clinical Trial of Single Dose Liposomal Bupivacaine Delivered Via VATS Intercostal Nerve Block vs. Continuous Bupivacaine Infusion Delivered Via Indwelling Subscapular Catheter After Surgical Stabilization of Rib Fractures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Denver Health and Hospital Authority</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Denver Health and Hospital Authority</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rib fractures represent a common injury pattern this is highly associated with patient&#xD;
      morbidity and mortality, as pain control remains a challenge. Even after surgical&#xD;
      stabilization of rib fractures (SSRF), unsuccessful pain control can lead to morbid outcomes&#xD;
      such as pneumonia and opioid dependence. Multi-modal anesthesia, with the use of thoracic&#xD;
      epidurals and para-vertebral injections/catheters, has shown to lessen these occurrences but&#xD;
      are subject to a wide array of limitations. A more directed therapy with liposomal&#xD;
      bupivacaine has shown to provide sustained analgesia for up to 72 hours in patients who have&#xD;
      undergone other types of thoracic surgery, but not SSRF. The hypothesis of the current&#xD;
      clinical trial is that, among patients undergoing SSRF, liposomal bupivacaine delivered via&#xD;
      video assisted thoracic surgery (VATS) is an intercostal nerve block that provides comparable&#xD;
      analgesia to the pain catheter, as measured by pulmonary function, numeric pain scoring, and&#xD;
      postoperative narcotic use.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rib fractures represent a common injury pattern with high associated morbidity and mortality.&#xD;
      Effective pain control in both the acute and long term periods remains a challenge. Surgical&#xD;
      stabilization of rib fractures (SSRF) is now a recommended treatment for patients with severe&#xD;
      chest wall injuries. In addition to stabilization of the chest wall, SSRF offers a unique&#xD;
      opportunity to deliver directed, loco-regional anesthesia. Loco-regional anesthesia is a&#xD;
      recognized, essential component of multi-modal anesthesia for patients with rib fractures in&#xD;
      order to both decrease pain and minimize the use of opioids and their associated side&#xD;
      effects.&#xD;
&#xD;
      Delivery options for loco-regional anesthesia to patients with rib fractures share in common&#xD;
      the intention of anesthetizing the intercostal nerves. Moving from the spinal cord laterally,&#xD;
      modalities include thoracic epidural catheters, paravertebral blocks or catheters, and&#xD;
      rib/intercostal blocks. Although rib blocks may be accomplished via a variety of techniques,&#xD;
      the two most common intra-operative techniques are video-assisted thoracoscopic surgery&#xD;
      (VATS) intercostal nerve blocks and indwelling, subscapular catheters In general, neuraxial&#xD;
      modalities such as thoracic epidural and para-vertebral injections/catheters are subject to a&#xD;
      wide array of limitations, including patient coagulopathy (International Normalized Ratio &gt;&#xD;
      1.5), co-existing spine fractures, peri-insertion, peri-removal withholding of venous&#xD;
      thromboembolism pharmacoprophylaxis, and provider availability. For these reasons, our&#xD;
      current practice is to insert a subscapular &quot;pain catheter&quot; at the conclusion of the SSRF&#xD;
      operation; this catheter is able to deliver a continuous infusion of 0.25% bupivacaine and&#xD;
      may be left in place for several days.&#xD;
&#xD;
      Although favorable results using the pain catheter have been published in patients with rib&#xD;
      fractures who have not undergone SSRF, we have noticed several limitations to this treatment&#xD;
      modality. First, position is highly variable; and, because the catheter is not truly in the&#xD;
      space of the intercostal nerves, drug delivery is likely irregular. This variability may be&#xD;
      particularly relevant in obese patients; and the median body mass index of patient who&#xD;
      underwent SSRF at Denver Health is 29 kg/m^2. Beyond catheter placement, we have also&#xD;
      experienced issues with leakage of drug from the skin entry site of the catheter. Moreover,&#xD;
      catheters frequently become dislodged or inadvertently removed during patient transport.&#xD;
      Further, the indwelling foreign body likely introduces some risk of infection. Finally, the&#xD;
      presence of the catheter is distressing to many patients.&#xD;
&#xD;
      Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc., Parsippany, NJ, www.pacira.com)&#xD;
      has been shown to provide sustained analgesia for up to 72 hours following a single injection&#xD;
      of the drug delivery system. The safety and efficacy of liposomal bupivacaine has been&#xD;
      evaluated in over 1,300 subjects and 21 clinical trials. Although many of these trials have&#xD;
      included thoracic surgery patients, no trial has evaluated the efficacy and safety of&#xD;
      liposomal bupivacaine administered to patients with rib fractures undergoing SSRF. Potential&#xD;
      benefits as compared to current practice include directed injection immediately adjacent to&#xD;
      the intercostal nerve using a VATS approach, as well as obviation of the need for an&#xD;
      indwelling catheter. The hypothesis of the current clinical trial is that, among patients&#xD;
      undergoing SSRF, liposomal bupivacaine delivered via video assisted thoracic surgery (VATS)&#xD;
      is an intercostal nerve block that provides comparable analgesia to the pain catheter, as&#xD;
      measured by pulmonary function, numeric pain scoring, and postoperative narcotic use.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 5, 2017</start_date>
  <completion_date type="Actual">January 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 20, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Non-inferiority, randomized, clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score</measure>
    <time_frame>Median SCARF scores were recorded for the first 5 postoperative days.</time_frame>
    <description>The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry &lt; 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Daily Narcotic Requirements Using Equi-analgesic Doses</measure>
    <time_frame>Mean narcotic requirement scores were recorded for the first 5 postoperative hospital inpatient days.</time_frame>
    <description>Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA)</measure>
    <time_frame>72 hours</time_frame>
    <description>The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Drug Effect</condition>
  <condition>Rib Fractures</condition>
  <condition>Rib Trauma</condition>
  <condition>Surgical Procedure, Unspecified</condition>
  <condition>Pain; Catheter (Other)</condition>
  <condition>Nerve Pain</condition>
  <condition>Local Infiltration</condition>
  <condition>Anesthesia, Local</condition>
  <condition>Intercostal Rib</condition>
  <condition>Opioid Dependence</condition>
  <condition>Chest Injury Trauma</condition>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Bupivacaine indwelling catheter</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liposomal bupivacaine injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal bupivacaine injection</intervention_name>
    <description>A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</description>
    <arm_group_label>Liposomal bupivacaine injection</arm_group_label>
    <other_name>Exparel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine indwelling catheter</intervention_name>
    <description>Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
    <arm_group_label>Bupivacaine indwelling catheter</arm_group_label>
    <other_name>OnQ pain pump, Continuous infusion of bupivacaine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing SSRF at Denver Health Medical Center&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy or hypersensitivity to bupivacaine&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Incarceration&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  Indwelling continuous thoracic epidural analgesia&#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>Fredric Pieracci, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Denver Health and Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Denver Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>October 4, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <results_first_submitted>July 8, 2021</results_first_submitted>
  <results_first_submitted_qc>August 2, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 25, 2021</results_first_posted>
  <last_update_submitted>September 2, 2021</last_update_submitted>
  <last_update_submitted_qc>September 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
    <mesh_term>Rib Fractures</mesh_term>
    <mesh_term>Thoracic Injuries</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 27, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT03305666/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited based on physician referral for surgical stabilization of rib fracture (SSRF) at Denver Health from November 2017 through July 2020.</recruitment_details>
      <pre_assignment_details>All 36 patients were enrolled in the study and assigned to groups via a Microsoft Excel randomization.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Bupivacaine Indwelling Catheter</title>
          <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours&#xD;
Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
        </group>
        <group group_id="P2">
          <title>Liposomal Bupivacaine Injection</title>
          <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).&#xD;
Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>ORIF cancelled due to patient's cognitive decline, withdrawn from study at this time</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline analysis did not include two patients who were withdrawn from the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Bupivacaine Indwelling Catheter</title>
          <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours&#xD;
Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
        </group>
        <group group_id="B2">
          <title>Liposomal Bupivacaine Injection</title>
          <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).&#xD;
Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</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="16"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.3" lower_limit="18" upper_limit="81"/>
                    <measurement group_id="B2" value="52.3" lower_limit="37" upper_limit="85"/>
                    <measurement group_id="B3" value="52.8" lower_limit="18" upper_limit="85"/>
                  </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="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</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>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26" lower_limit="20.4" upper_limit="34.8"/>
                    <measurement group_id="B2" value="27.2" lower_limit="16.45" upper_limit="36.8"/>
                    <measurement group_id="B3" value="26.6" lower_limit="16.45" upper_limit="36.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Injury Severity Score (ISS)</title>
          <description>The total range of the Injury Severity Score (ISS) is from 0-75, with a score of 0 being the best and indicating no injury at all and a score of 75 being the worst and indicating a fatal injury. Six major body regions are scored by a physician on a scale of 0-6 and the body regions with the three most severe injury scores are squared and summed to result in the final 0-75 score. However, if any of the three scores is a 6, the final score is automatically set at 75.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.5" lower_limit="9" upper_limit="38"/>
                    <measurement group_id="B2" value="22.1" lower_limit="9" upper_limit="38"/>
                    <measurement group_id="B3" value="20.8" lower_limit="9" upper_limit="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with Asthma</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with COPD</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants who Use Tobacco</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Admit Glasgow Coma Scale (GCS)</title>
          <description>The Glasgow Coma Scale (GCS) is a measure of consciousness scale examining patients' degree of responsiveness regarding eye opening, verbal communication, and motor functioning. The GCS scores have a range of 3-15, with a 3 being the worst score and a 15 being the best. Eye opening is scored from 1-4, verbal communication is scored from 1-5, and motor functioning is scored from 1-6. The three scored categories are summed to arrive at the total score, averaged across patients below.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.3" lower_limit="3" upper_limit="15"/>
                    <measurement group_id="B2" value="13.3" lower_limit="3" upper_limit="15"/>
                    <measurement group_id="B3" value="13.3" lower_limit="3" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score</title>
        <description>The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry &lt; 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.</description>
        <time_frame>Median SCARF scores were recorded for the first 5 postoperative days.</time_frame>
        <population>All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. Patients who were intubated at 10 am (the time of data reporting) could not be measured on a few factors of this outcome measure and this discrepancy was accounted for in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine Indwelling Catheter</title>
            <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours&#xD;
Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
          </group>
          <group group_id="O2">
            <title>Liposomal Bupivacaine Injection</title>
            <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).&#xD;
Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score</title>
          <description>The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry &lt; 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.</description>
          <population>All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. Patients who were intubated at 10 am (the time of data reporting) could not be measured on a few factors of this outcome measure and this discrepancy was accounted for in the statistical analysis.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="0" upper_limit="4"/>
                    <measurement group_id="O2" value="2" lower_limit="0" upper_limit="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>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conduced using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.12</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Narcotic Requirements Using Equi-analgesic Doses</title>
        <description>Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.</description>
        <time_frame>Mean narcotic requirement scores were recorded for the first 5 postoperative hospital inpatient days.</time_frame>
        <population>All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. The data below is the mean result provided for each of the first 5 postoperative days following surgical intervention.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine Indwelling Catheter</title>
            <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours&#xD;
Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
          </group>
          <group group_id="O2">
            <title>Liposomal Bupivacaine Injection</title>
            <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).&#xD;
Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Narcotic Requirements Using Equi-analgesic Doses</title>
          <description>Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.</description>
          <population>All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. The data below is the mean result provided for each of the first 5 postoperative days following surgical intervention.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Postoperative Day #1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.8" spread="13"/>
                    <measurement group_id="O2" value="6.5" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Postoperative Day #2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="10.1"/>
                    <measurement group_id="O2" value="4.0" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Postoperative Day #3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="6.1"/>
                    <measurement group_id="O2" value="2.6" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Postoperative Day #4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="5.7"/>
                    <measurement group_id="O2" value="1.6" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Postoperative Day #5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="7.4"/>
                    <measurement group_id="O2" value="2.2" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This is the P-Value for between groups comparison of Postoperative Day #1.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conducted using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.41</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This is the P-Value for between groups comparison of Postoperative Day #2.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conducted using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.25</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This is the P-Value for between groups comparison of Postoperative Day #3.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conducted using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.12</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This is the P-Value for between groups comparison of Postoperative Day #4.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conducted using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.04</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This is the P-Value for between groups comparison of Postoperative Day #5.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conducted using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.32</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA)</title>
        <description>The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.</description>
        <time_frame>72 hours</time_frame>
        <population>All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. Percentages entered below are based on number of failure occurrences, in this case defined as requiring a secondary LRA.</population>
        <group_list>
          <group group_id="O1">
            <title>Bupivacaine Indwelling Catheter</title>
            <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours&#xD;
Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
          </group>
          <group group_id="O2">
            <title>Liposomal Bupivacaine Injection</title>
            <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).&#xD;
Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA)</title>
          <description>The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.</description>
          <population>All 34 participants were analyzed on this data point and aggregate data is provided below for each treatment arm. Percentages entered below are based on number of failure occurrences, in this case defined as requiring a secondary LRA.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.8"/>
                    <measurement group_id="O2" value="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Statistical analyses were conduced using SAS version 9.4. This non-inferiority test was conducted via a one-way ANOVA test, with statistical significance set at p &lt; 0.05.</non_inferiority_desc>
            <p_value>0.23</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bupivacaine Indwelling Catheter</title>
          <description>Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours&#xD;
Bupivacaine indwelling catheter: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op</description>
        </group>
        <group group_id="E2">
          <title>Liposomal Bupivacaine Injection</title>
          <description>A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).&#xD;
Liposomal bupivacaine injection: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </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="3" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hospital Readmission</sub_title>
                <description>Chronic subdural hematoma requiring evacuation; not study related.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>OR Takeback</sub_title>
                <description>Evacuation of incisional hematoma</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Hospital Readmission</sub_title>
                <description>EtOH Withdrawal; not study related.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>ED Visit</sub_title>
                <description>Acute EtOH intoxication, complaint of rib pain, however no admission.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>There were no limitations that created barriers to the completion of this project. While this was expected at the outset of this exploratory trial, there was a relatively small sample size with a wide range of fractures for individual participants. Underpowering likely limited analyses of secondary outcomes such as narcotic requirements and failure of LRA. The study also excluded patients with GCS &lt; 8, so caution should be exercised when extrapolating to mechanically ventilated patients.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Fredric Pieracci</name_or_title>
      <organization>Denver Health and Hospital Authority</organization>
      <phone>(303) 436-4029</phone>
      <email>Fredric.Pieracci@dhha.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/NCT03305666
org study id: 17-0685
nct id: NCT03305666
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Rib fractures represent a common injury pattern this is highly associated with patient
      morbidity and mortality, as pain control remains a challenge. Even after surgical
      stabilization of rib fractures (SSRF), unsuccessful pain control can lead to morbid outcomes
      such as pneumonia and opioid dependence. Multi-modal anesthesia, with the use of thoracic
      epidurals and para-vertebral injections/catheters, has shown to lessen these occurrences but
      are subject to a wide array of limitations. A more directed therapy with liposomal
      bupivacaine has shown to provide sustained analgesia for up to 72 hours in patients who have
      undergone other types of thoracic surgery, but not SSRF. The hypothesis of the current
      clinical trial is that, among patients undergoing SSRF, liposomal bupivacaine delivered via
      video assisted thoracic surgery (VATS) is an intercostal nerve block that provides comparable
      analgesia to the pain catheter, as measured by pulmonary function, numeric pain scoring, and
      postoperative narcotic use.
Rib fractures represent a common injury pattern with high associated morbidity and mortality.
      Effective pain control in both the acute and long term periods remains a challenge. Surgical
      stabilization of rib fractures (SSRF) is now a recommended treatment for patients with severe
      chest wall injuries. In addition to stabilization of the chest wall, SSRF offers a unique
      opportunity to deliver directed, loco-regional anesthesia. Loco-regional anesthesia is a
      recognized, essential component of multi-modal anesthesia for patients with rib fractures in
      order to both decrease pain and minimize the use of opioids and their associated side
      effects.

      Delivery options for loco-regional anesthesia to patients with rib fractures share in common
      the intention of anesthetizing the intercostal nerves. Moving from the spinal cord laterally,
      modalities include thoracic epidural catheters, paravertebral blocks or catheters, and
      rib/intercostal blocks. Although rib blocks may be accomplished via a variety of techniques,
      the two most common intra-operative techniques are video-assisted thoracoscopic surgery
      (VATS) intercostal nerve blocks and indwelling, subscapular catheters In general, neuraxial
      modalities such as thoracic epidural and para-vertebral injections/catheters are subject to a
      wide array of limitations, including patient coagulopathy (International Normalized Ratio >
      1.5), co-existing spine fractures, peri-insertion, peri-removal withholding of venous
      thromboembolism pharmacoprophylaxis, and provider availability. For these reasons, our
      current practice is to insert a subscapular "pain catheter" at the conclusion of the SSRF
      operation; this catheter is able to deliver a continuous infusion of 0.25% bupivacaine and
      may be left in place for several days.

      Although favorable results using the pain catheter have been published in patients with rib
      fractures who have not undergone SSRF, we have noticed several limitations to this treatment
      modality. First, position is highly variable; and, because the catheter is not truly in the
      space of the intercostal nerves, drug delivery is likely irregular. This variability may be
      particularly relevant in obese patients; and the median body mass index of patient who
      underwent SSRF at Denver Health is 29 kg/m^2. Beyond catheter placement, we have also
      experienced issues with leakage of drug from the skin entry site of the catheter. Moreover,
      catheters frequently become dislodged or inadvertently removed during patient transport.
      Further, the indwelling foreign body likely introduces some risk of infection. Finally, the
      presence of the catheter is distressing to many patients.

      Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc., Parsippany, NJ, www.pacira.com)
      has been shown to provide sustained analgesia for up to 72 hours following a single injection
      of the drug delivery system. The safety and efficacy of liposomal bupivacaine has been
      evaluated in over 1,300 subjects and 21 clinical trials. Although many of these trials have
      included thoracic surgery patients, no trial has evaluated the efficacy and safety of
      liposomal bupivacaine administered to patients with rib fractures undergoing SSRF. Potential
      benefits as compared to current practice include directed injection immediately adjacent to
      the intercostal nerve using a VATS approach, as well as obviation of the need for an
      indwelling catheter. The hypothesis of the current clinical trial is that, among patients
      undergoing SSRF, liposomal bupivacaine delivered via video assisted thoracic surgery (VATS)
      is an intercostal nerve block that provides comparable analgesia to the pain catheter, as
      measured by pulmonary function, numeric pain scoring, and postoperative narcotic use.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Non-inferiority, randomized, clinical trial
primary purpose: Treatment
masking: None (Open Label)
measure: Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score
time frame: Median SCARF scores were recorded for the first 5 postoperative days.
description: The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry < 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.
measure: Daily Narcotic Requirements Using Equi-analgesic Doses
time frame: Mean narcotic requirement scores were recorded for the first 5 postoperative hospital inpatient days.
description: Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.
measure: Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA)
time frame: 72 hours
description: The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.
arm group label: Bupivacaine indwelling catheter
arm group type: Active Comparator
description: Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours
arm group label: Liposomal bupivacaine injection
arm group type: Active Comparator
description: A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).
intervention type: Drug
intervention name: Liposomal bupivacaine injection
description: A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
arm group label: Liposomal bupivacaine injection
other name: Exparel
intervention type: Drug
intervention name: Bupivacaine indwelling catheter
description: Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op
arm group label: Bupivacaine indwelling catheter
other name: OnQ pain pump, Continuous infusion of bupivacaine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Fredric Pieracci, MD MPH
role: Principal Investigator
affiliation: Denver Health and Hospital
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neuralgia
mesh term: Opioid-Related Disorders
mesh term: Fractures, Bone
mesh term: Wounds and Injuries
mesh term: Rib Fractures
mesh term: Thoracic Injuries
mesh term: Bupivacaine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There were no limitations that created barriers to the completion of this project. While this was expected at the outset of this exploratory trial, there was a relatively small sample size with a wide range of fractures for individual participants. Underpowering likely limited analyses of secondary outcomes such as narcotic requirements and failure of LRA. The study also excluded patients with GCS < 8, so caution should be exercised when extrapolating to mechanically ventilated patients.
point of contact: 