<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/NCT02969187</url>
  </required_header>
  <id_info>
    <org_study_id>15-1318</org_study_id>
    <nct_id>NCT02969187</nct_id>
  </id_info>
  <brief_title>Bupivacaine Liposomal Injection (Exparel) for Postsurgical Analgesia in Patient Undergoing Laparoscopic Bariatric Surgery</brief_title>
  <official_title>Bupivacaine Liposomal Injection (Exparel) for Postsurgical Analgesia in Patients Undergoing Laparoscopic Bariatric Surgery: A Randomized, Double-Blind, Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Despite the increasing use of patient-controlled anesthesia (PCA) for postoperative pain&#xD;
      management, efforts are continuing to find effective methods to relieve pain after abdominal&#xD;
      surgery. Although opioid is an effective analgesic it has opioid related adverse events&#xD;
      (ORAEs). Bupivacaine should reduce postoperative pain but it has relatively shorter duration&#xD;
      of action. Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for&#xD;
      longer postoperative period analgesic. It provides up to 72 hours analgesia postoperatively;&#xD;
      results in lesser opioids usage and reduce the ORAEs. Transversus abdominis plane (TAP) block&#xD;
      is a relatively new regional anesthetic technique. TAP blocks have been performed to reduce&#xD;
      opioid use and control pain in several laparoscopic surgical procedures, including colorectal&#xD;
      resections, cholecystectomy and bariatric surgery. The aim of this study is to study the&#xD;
      opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve gastrectomy using&#xD;
      Exparel versus Bupivacaine as TAP block and port sites infiltration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction&#xD;
&#xD;
      Despite the increasing use of patient-controlled anesthesia (PCA) for postoperative pain&#xD;
      management, efforts are continuing to find effective methods to relieve pain after abdominal&#xD;
      surgery. Some studies have already suggested that infusion with local anesthetics at the&#xD;
      wound site can decrease postoperative pain levels. Further, other studies have shown equal&#xD;
      amounts of opiate analgesic requirements (administered on patient demand) with placebo and&#xD;
      local anesthetic administration. However, varying anesthetic administration techniques used&#xD;
      in the different studies may explain why the controversy in the literature exists.&#xD;
&#xD;
      Although opioid is an effective analgesic it has opioid related adverse events (ORAEs).&#xD;
      Bupivacaine should reduce postoperative pain but it has relatively shorter duration of&#xD;
      action. Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for&#xD;
      longer postoperative period analgesic. It provides up to 72 hours analgesia postoperatively;&#xD;
      results in lesser opioids usage and reduce the ORAEs.&#xD;
&#xD;
      Transversus abdominis plane (TAP) block is a relatively new regional anesthetic technique&#xD;
      that targets blockage of the neural afferent of the lower intercostal, iliohypogastric and&#xD;
      ilioinguinal nerves in the neurovascular plane between the internal oblique and the&#xD;
      transversus abdominis muscle. TAP blocks have been performed to reduce opioid use and control&#xD;
      pain in several laparoscopic surgical procedures, including colorectal resections,&#xD;
      cholecystectomy and bariatric surgery.&#xD;
&#xD;
      Efficacy of wound infiltration with or without TAP block using immediate-release bupivacaine&#xD;
      HCl for acute postsurgical pain is well established; EXPAREL has been proposed as a method&#xD;
      for postoperative pain management. Moreover, the administration and the optimal dosage in the&#xD;
      bariatric surgical population have not been studied.&#xD;
&#xD;
      The objective of this study is to examine postoperative pain after laparoscopic gastric&#xD;
      bypass with TAP block and port sites infiltration using Exparel versus Bupivacaine&#xD;
&#xD;
      Background and significance&#xD;
&#xD;
      Exparel is a FDA approved long-acting, local anesthetic. This is for single-dose infiltration&#xD;
      into the surgical site to produce postsurgical analgesia. Exparel offers longer-acting local&#xD;
      formulation and can be administered as a single dose. Exparel has a longer duration of action&#xD;
      with slower absorption. The mean elimination half-life of local administration of Exparel is&#xD;
      approximately 24-34 hours 19-20 versus 2.7 hours for bupivacaine.&#xD;
&#xD;
      Liposomal bupivacaine is for single-dose infiltration and the recommended dose depends on the&#xD;
      surgical site but the maximum dose of liposomal bupivacaine is 266 mg and it is injected into&#xD;
      soft tissues of the surgical site with frequent aspirations to prevent intravascular&#xD;
      injection.&#xD;
&#xD;
      A pooled analysis evaluating the effect of Exparel on pain intensity scores and opioid&#xD;
      consumption was published by Dasta et al. This study included 5 surgical procedures (inguinal&#xD;
      hernia repair, total knee replacement, hemorrhoidectomy, breast augmentation and&#xD;
      bunionectomy) comparing Exparel with bupivacaine HCl, on 912 patients; it showed&#xD;
      significantly lower pain score and opioid usage, delayed use of rescue opioid and reduced&#xD;
      ORAEs in the Exparel group; as compared to bupivacaine HCL group.&#xD;
&#xD;
      Medication SafetLiposomal bupivacaine has been classified as a high-alert medication by the&#xD;
      Institute of Safe Medication Practices due to its similar appearance to propofol. If&#xD;
      liposomal bupivacaine were administered intravenously as if it were propofol, adverse cardiac&#xD;
      effects may result.&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      Exparel (1.3%) and 0.5% Bupivacaine usage with infiltration and TAP block decreases opiate&#xD;
      usage, nausea and pain at 48 hours as compared to 0.5% Bupivacaine only.&#xD;
&#xD;
      Primary Objective of the study:&#xD;
&#xD;
      To study the opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve&#xD;
      gastrectomy using EXPAREL versus Bupivacaine as TAP block and port sites infiltration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">March 31, 2018</completion_date>
  <primary_completion_date type="Actual">January 31, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Amount of Opioids at 48 Hours</measure>
    <time_frame>At 48 hours post operative</time_frame>
    <description>The total amount of opioids used will be recorded from the nurse chart.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative Pain Score Through 48 Hours After Surgery</measure>
    <time_frame>Pain assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 48 hours post operatively</time_frame>
    <description>Description: We used a time weight average (TWA) pain score in frequent measurements of pain score.&#xD;
Cumulative pain score through 48 hours after surgery is the summation of all the time weight average pain scores with a range from 0 to 440.&#xD;
The high score represents the worse outcomes. 0 means no pain during the whole time and 440 means severe pain during the whole time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Nausea Score</measure>
    <time_frame>Nausea assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 72 hours post operatively</time_frame>
    <description>Description: We used a time weight average (TWA) method in adjusting the nausea score.&#xD;
Cumulative nausea score through 72 hours after surgery is the summation of all the time weight average nausea scores with a range from 68-272.&#xD;
The high score represents the worse outcomes. 68 means no nausea during the whole time and 272 means severe nausea during the whole time.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exparel</intervention_name>
    <description>6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites.</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacain</intervention_name>
    <description>6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fulfills NIH criteria for bariatric surgery&#xD;
&#xD;
          -  Planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic&#xD;
             sleeve gastrectomy (LSG) as primary bariatric procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &lt;35 and &gt; 60 kg/m2&#xD;
&#xD;
          -  Inability to walk (bed-bound or wheelchair dependence)&#xD;
&#xD;
          -  Previous major abdominal surgery (possible adhesions and longer operation) defined as:&#xD;
&#xD;
               -  open abdominal surgeries except simple appendectomy and common OB/GYN procedures&#xD;
                  in the pelvis (hysterectomy, C-section, and oophorectomy, tubal ligation)&#xD;
&#xD;
               -  laparoscopic bowel or solid organ resection except laparoscopic cholecystectomy&#xD;
&#xD;
               -  ventral hernia repair with mesh&#xD;
&#xD;
          -  Preoperative chronic opiate use for chronic pain defined as opiate usage at least 60&#xD;
             mg/day of morphine equivalent for ≥ 3 months (as defined by International Association&#xD;
             for the Study of Pain22) in the one year period prior to the bariatric surgery&#xD;
&#xD;
          -  The American Society of Anesthesiologists (ASA) score &gt; 3&#xD;
&#xD;
          -  History of hypersensitivity or adverse reaction to bupivacaine or narcotics&#xD;
&#xD;
          -  Inability to speak English&#xD;
&#xD;
          -  Concurrent surgical procedure including:&#xD;
&#xD;
               -  ventral hernia repair&#xD;
&#xD;
               -  Cholecystectomy&#xD;
&#xD;
               -  hiatal hernia repair with posterior cruroplasty&#xD;
&#xD;
               -  extensive lysis of adhesions&#xD;
&#xD;
               -  other procedures that mandate addition of &quot;trocar(s)&quot; or &quot;feeding tube&quot;&#xD;
&#xD;
          -  Addition of trocar(s) or conversion of surgery to hand-assisted or open&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>November 9, 2016</study_first_submitted>
  <study_first_submitted_qc>November 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <results_first_submitted>July 9, 2019</results_first_submitted>
  <results_first_submitted_qc>February 19, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 3, 2020</results_first_posted>
  <last_update_submitted>February 19, 2020</last_update_submitted>
  <last_update_submitted_qc>February 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Philip Schauer</investigator_full_name>
    <investigator_title>Staff Surgeon</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>
  <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>November 23, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02969187/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Experimental</title>
          <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm.&#xD;
6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars.&#xD;
Study arm receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline (total: 200ml)&#xD;
Transverse Abdominis Plane (TAP) block: 140 ml&#xD;
Port site infiltration:60ml</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm.&#xD;
6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars.&#xD;
Control arm receive 60ml of 0.5% Bupivacaine + 140 ml of Saline (total: 200ml)&#xD;
Transverse Abdominis Plane (TAP) block: 140 ml&#xD;
Port site infiltration:60ml</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
                <participants group_id="P2" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>A total of 101 patients were included; Bupivacaine alone (n=50) and Liposome bupivacaine and bupivacaine (n=51) with a follow up period of 1-month.</population>
      <group_list>
        <group group_id="B1">
          <title>Experimental</title>
          <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline&#xD;
Exparel: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites.&#xD;
Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.&#xD;
Saline</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline.&#xD;
Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.&#xD;
Saline</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="51"/>
            <count group_id="B2" value="50"/>
            <count group_id="B3" value="101"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="51"/>
                    <count group_id="B2" value="50"/>
                    <count group_id="B3" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.1" lower_limit="32.5" upper_limit="48.4"/>
                    <measurement group_id="B2" value="41.2" lower_limit="33.7" upper_limit="46.8"/>
                    <measurement group_id="B3" value="41.1" lower_limit="32.5" upper_limit="48.4"/>
                  </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="51"/>
                    <count group_id="B2" value="50"/>
                    <count group_id="B3" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </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>BMI</title>
          <description>Body mass index</description>
          <units>kg/m2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="51"/>
                    <count group_id="B2" value="50"/>
                    <count group_id="B3" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44" lower_limit="41" upper_limit="48"/>
                    <measurement group_id="B2" value="44" lower_limit="42" upper_limit="52"/>
                    <measurement group_id="B3" value="44" lower_limit="41" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Amount of Opioids at 48 Hours</title>
        <description>The total amount of opioids used will be recorded from the nurse chart.</description>
        <time_frame>At 48 hours post operative</time_frame>
        <population>A total of 126 patients were randomized in this study. Out of that, 25 patients were excluded due either inadequate data, not prescribed post-operative ketorolac or intraoperative additional procedures performed. A total of 101 patients were included;</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental</title>
            <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline&#xD;
Exparel: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites.&#xD;
Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.&#xD;
Saline</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline.&#xD;
Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.&#xD;
Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Total Amount of Opioids at 48 Hours</title>
          <description>The total amount of opioids used will be recorded from the nurse chart.</description>
          <population>A total of 126 patients were randomized in this study. Out of that, 25 patients were excluded due either inadequate data, not prescribed post-operative ketorolac or intraoperative additional procedures performed. A total of 101 patients were included;</population>
          <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="51"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.5" spread="17.1"/>
                    <measurement group_id="O2" value="27.1" spread="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Pain Score Through 48 Hours After Surgery</title>
        <description>Description: We used a time weight average (TWA) pain score in frequent measurements of pain score.&#xD;
Cumulative pain score through 48 hours after surgery is the summation of all the time weight average pain scores with a range from 0 to 440.&#xD;
The high score represents the worse outcomes. 0 means no pain during the whole time and 440 means severe pain during the whole time.</description>
        <time_frame>Pain assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 48 hours post operatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Experimental</title>
            <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm.&#xD;
6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars.&#xD;
Study arm receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline (total: 200ml)&#xD;
Transverse Abdominis Plane (TAP) block: 140 ml&#xD;
Port site infiltration:60ml</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm.&#xD;
6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars.&#xD;
Control arm receive 60ml of 0.5% Bupivacaine + 140 ml of Saline (total: 200ml)&#xD;
Transverse Abdominis Plane (TAP) block: 140 ml&#xD;
Port site infiltration:60ml</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Pain Score Through 48 Hours After Surgery</title>
          <description>Description: We used a time weight average (TWA) pain score in frequent measurements of pain score.&#xD;
Cumulative pain score through 48 hours after surgery is the summation of all the time weight average pain scores with a range from 0 to 440.&#xD;
The high score represents the worse outcomes. 0 means no pain during the whole time and 440 means severe pain during the whole time.</description>
          <units>score 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="51"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="177.0" spread="62.9"/>
                    <measurement group_id="O2" value="167.8" spread="62.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Nausea Score</title>
        <description>Description: We used a time weight average (TWA) method in adjusting the nausea score.&#xD;
Cumulative nausea score through 72 hours after surgery is the summation of all the time weight average nausea scores with a range from 68-272.&#xD;
The high score represents the worse outcomes. 68 means no nausea during the whole time and 272 means severe nausea during the whole time.</description>
        <time_frame>Nausea assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 72 hours post operatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Experimental</title>
            <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm.&#xD;
6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars.&#xD;
Study arm receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline (total: 200ml)&#xD;
Transverse Abdominis Plane (TAP) block: 140 ml&#xD;
Port site infiltration:60ml</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm.&#xD;
6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars.&#xD;
Control arm receive 60ml of 0.5% Bupivacaine + 140 ml of Saline (total: 200ml)&#xD;
Transverse Abdominis Plane (TAP) block: 140 ml&#xD;
Port site infiltration:60ml</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Nausea Score</title>
          <description>Description: We used a time weight average (TWA) method in adjusting the nausea score.&#xD;
Cumulative nausea score through 72 hours after surgery is the summation of all the time weight average nausea scores with a range from 68-272.&#xD;
The high score represents the worse outcomes. 68 means no nausea during the whole time and 272 means severe nausea during the whole time.</description>
          <units>score 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="51"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79" spread="12"/>
                    <measurement group_id="O2" value="98" spread="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Two patients in the study arm developed urticarial rashes over the abdominal wall at the site of injection. Their rashes were noticed on day 7 after the procedure during follow up visit in the clinic by the attending physician.</time_frame>
      <desc>Two patients in the study arm developed urticarial rash over the abdominal wall at the site on injection noticed at 1 week post procedure during follow up visit. The rash noticed at 1 week post procedure during follow up visit. The rash was itchy but limited only to the abdominal area at the injection site.&#xD;
No other adverse events noted. At subsequent follow up, the rash has resolved.</desc>
      <group_list>
        <group group_id="E1">
          <title>Experimental</title>
          <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline&#xD;
Exparel: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites.&#xD;
Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.&#xD;
Saline</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline.&#xD;
Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.&#xD;
Saline</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="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Minor adverse event</sub_title>
                <description>Two patients in the study arm developed urticarial rash over the abdominal wall at the site on injection. The rash was itchy but limited only to the abdominal area at the injection site. At subsequent follow up, the rash has resolved.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
              </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 is no data available to guide us on the dosage of liposome bupivacaine in bariatric surgery. We assume adequate quantity and coverage of liposome bupivacaine (266mg) in this obese population, despite that they have a bigger surface area.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Philip R. Schauer</name_or_title>
      <organization>Cleveland Clinic</organization>
      <phone>216-444-4794</phone>
      <email>schauep@ccf.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/NCT02969187
org study id: 15-1318
nct id: NCT02969187
lead sponsor: 
has dmc: No
Despite the increasing use of patient-controlled anesthesia (PCA) for postoperative pain
      management, efforts are continuing to find effective methods to relieve pain after abdominal
      surgery. Although opioid is an effective analgesic it has opioid related adverse events
      (ORAEs). Bupivacaine should reduce postoperative pain but it has relatively shorter duration
      of action. Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for
      longer postoperative period analgesic. It provides up to 72 hours analgesia postoperatively;
      results in lesser opioids usage and reduce the ORAEs. Transversus abdominis plane (TAP) block
      is a relatively new regional anesthetic technique. TAP blocks have been performed to reduce
      opioid use and control pain in several laparoscopic surgical procedures, including colorectal
      resections, cholecystectomy and bariatric surgery. The aim of this study is to study the
      opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve gastrectomy using
      Exparel versus Bupivacaine as TAP block and port sites infiltration.
Introduction

      Despite the increasing use of patient-controlled anesthesia (PCA) for postoperative pain
      management, efforts are continuing to find effective methods to relieve pain after abdominal
      surgery. Some studies have already suggested that infusion with local anesthetics at the
      wound site can decrease postoperative pain levels. Further, other studies have shown equal
      amounts of opiate analgesic requirements (administered on patient demand) with placebo and
      local anesthetic administration. However, varying anesthetic administration techniques used
      in the different studies may explain why the controversy in the literature exists.

      Although opioid is an effective analgesic it has opioid related adverse events (ORAEs).
      Bupivacaine should reduce postoperative pain but it has relatively shorter duration of
      action. Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for
      longer postoperative period analgesic. It provides up to 72 hours analgesia postoperatively;
      results in lesser opioids usage and reduce the ORAEs.

      Transversus abdominis plane (TAP) block is a relatively new regional anesthetic technique
      that targets blockage of the neural afferent of the lower intercostal, iliohypogastric and
      ilioinguinal nerves in the neurovascular plane between the internal oblique and the
      transversus abdominis muscle. TAP blocks have been performed to reduce opioid use and control
      pain in several laparoscopic surgical procedures, including colorectal resections,
      cholecystectomy and bariatric surgery.

      Efficacy of wound infiltration with or without TAP block using immediate-release bupivacaine
      HCl for acute postsurgical pain is well established; EXPAREL has been proposed as a method
      for postoperative pain management. Moreover, the administration and the optimal dosage in the
      bariatric surgical population have not been studied.

      The objective of this study is to examine postoperative pain after laparoscopic gastric
      bypass with TAP block and port sites infiltration using Exparel versus Bupivacaine

      Background and significance

      Exparel is a FDA approved long-acting, local anesthetic. This is for single-dose infiltration
      into the surgical site to produce postsurgical analgesia. Exparel offers longer-acting local
      formulation and can be administered as a single dose. Exparel has a longer duration of action
      with slower absorption. The mean elimination half-life of local administration of Exparel is
      approximately 24-34 hours 19-20 versus 2.7 hours for bupivacaine.

      Liposomal bupivacaine is for single-dose infiltration and the recommended dose depends on the
      surgical site but the maximum dose of liposomal bupivacaine is 266 mg and it is injected into
      soft tissues of the surgical site with frequent aspirations to prevent intravascular
      injection.

      A pooled analysis evaluating the effect of Exparel on pain intensity scores and opioid
      consumption was published by Dasta et al. This study included 5 surgical procedures (inguinal
      hernia repair, total knee replacement, hemorrhoidectomy, breast augmentation and
      bunionectomy) comparing Exparel with bupivacaine HCl, on 912 patients; it showed
      significantly lower pain score and opioid usage, delayed use of rescue opioid and reduced
      ORAEs in the Exparel group; as compared to bupivacaine HCL group.

      Medication SafetLiposomal bupivacaine has been classified as a high-alert medication by the
      Institute of Safe Medication Practices due to its similar appearance to propofol. If
      liposomal bupivacaine were administered intravenously as if it were propofol, adverse cardiac
      effects may result.

      Hypothesis

      Exparel (1.3%) and 0.5% Bupivacaine usage with infiltration and TAP block decreases opiate
      usage, nausea and pain at 48 hours as compared to 0.5% Bupivacaine only.

      Primary Objective of the study:

      To study the opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve
      gastrectomy using EXPAREL versus Bupivacaine as TAP block and port sites infiltration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Total Amount of Opioids at 48 Hours
time frame: At 48 hours post operative
description: The total amount of opioids used will be recorded from the nurse chart.
measure: Cumulative Pain Score Through 48 Hours After Surgery
time frame: Pain assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 48 hours post operatively
description: Description: We used a time weight average (TWA) pain score in frequent measurements of pain score.
Cumulative pain score through 48 hours after surgery is the summation of all the time weight average pain scores with a range from 0 to 440.
The high score represents the worse outcomes. 0 means no pain during the whole time and 440 means severe pain during the whole time.
measure: Cumulative Nausea Score
time frame: Nausea assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 72 hours post operatively
description: Description: We used a time weight average (TWA) method in adjusting the nausea score.
Cumulative nausea score through 72 hours after surgery is the summation of all the time weight average nausea scores with a range from 68-272.
The high score represents the worse outcomes. 68 means no nausea during the whole time and 272 means severe nausea during the whole time.
arm group label: Experimental
arm group type: Experimental
description: Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline
arm group label: Control
arm group type: Active Comparator
description: Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline.
intervention type: Drug
intervention name: Exparel
description: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites.
arm group label: Experimental
intervention type: Drug
intervention name: Bupivacain
description: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.
arm group label: Control
arm group label: Experimental
intervention type: Drug
intervention name: Saline
arm group label: Control
arm group label: Experimental
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Philip Schauer
investigator title: Staff Surgeon
mesh term: Pain, Postoperative
mesh term: Bupivacaine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There is no data available to guide us on the dosage of liposome bupivacaine in bariatric surgery. We assume adequate quantity and coverage of liposome bupivacaine (266mg) in this obese population, despite that they have a bigger surface area.
point of contact: 