<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/NCT03769714</url>
  </required_header>
  <id_info>
    <org_study_id>2018-02-12-MMC</org_study_id>
    <nct_id>NCT03769714</nct_id>
  </id_info>
  <brief_title>EXPAREL for Minimally Invasive Supracervical Hysterectomies</brief_title>
  <official_title>A Placebo-controlled, Double-blinded, Randomized Pilot Study of Bupivacaine Liposome Injectable Suspension (EXPAREL) for Minimally Invasive Supracervical Hysterectomies Postsurgical Analgesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maimonides Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maimonides Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the of the study is a reduction in minimally invasive supracervical hysterectomy&#xD;
      postsurgical pain, which may result in less need for supplemental opioid pain medications,&#xD;
      fewer opioid related adverse events, and a better recovery experience for patients, which may&#xD;
      offer an economic benefit to health care systems.&#xD;
&#xD;
      Intracervical preoperative dose of Exparel during minimally invasive (robotic--assisted or&#xD;
      traditional laparoscopy) supracervical hysterectomy reduces cumulative pain scores for up to&#xD;
      24 hours and reduces overall requests for break through (additional) analgesia with opioid&#xD;
      consumption compared with placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Exparel is a local analgesic that utilizes bupivacaine in combination with the proven product&#xD;
      delivery platform, DepoFoam®. Exparel (bupivacaine liposome injectable suspension) is a&#xD;
      liposome injection of bupivacaine, an amide-type local anesthetic, indicated (bupivacaine&#xD;
      liposome injectable suspension) for administration into the surgical site to produce&#xD;
      postsurgical analgesia. Liposomal drug- containing formulations can provide for controlled&#xD;
      drug release over an extended period of time.&#xD;
&#xD;
      The overall length of hospital stay (LOS) for patients undergoing laparoscopic (robot-&#xD;
      assisted or traditional laparoscopy) supracervical hysterectomy varies widely in published&#xD;
      reports; typical durations range between 0 days and 4 days.&#xD;
&#xD;
      That is because in recent years there has been a trend toward use of enhanced or &quot;fast-&#xD;
      track&quot; discharge protocols to reduce LOS in patients undergoing this procedure, predicated&#xD;
      primarily on reducing the time to achieve tolerance of oral liquid/food intake and improved&#xD;
      GI function. Most patients experience moderate to extreme pain after surgery and effective&#xD;
      postsurgical pain management is a key factor affecting patient recovery. Multimodal analgesia&#xD;
      techniques involving analgesics, such as local anesthetics, oral or parenteral nonsteroidal&#xD;
      anti-inflammatory medications, and oral or parenteral opioids, are recommended as the safest&#xD;
      and effective approach to postsurgical pain control. Local anesthetics administered during&#xD;
      surgery are frequently used as part of multimodal analgesic regimens; however, the duration&#xD;
      of analgesia with these agents is short (12 hours). Bupivacaine has a long history of use in&#xD;
      the surgical setting, and the efficacy of bupivacaine HCl administered perioperatively via&#xD;
      wound infiltration or acute postsurgical pain is well established. A novel formulation of&#xD;
      bupivacaine, ie, liposome bupivacaine (Pacira Pharmaceuticals, Inc., Parsippany, NJ), has&#xD;
      been developed to address the need for longer-acting local anesthetics that can be&#xD;
      administered as a single dose. The question becomes whether this drug is effective for&#xD;
      postsurgical analgesia if given preoperatively via the intracervical stroma during minimally&#xD;
      invasive gynecologic surgical procedures, specifically laparoscopic (robot--assisted or&#xD;
      traditional laparoscopy) supracervical hysterectomy.&#xD;
&#xD;
      Paracervical/intracervical injections are used for cervical/uterine manipulation in various&#xD;
      obstetrical and gynecological procedures. Lukas et al used the intracervical/paracervical&#xD;
      block prior to hysteroscopic polypectomy, with good pain scores following the procedure and&#xD;
      no serious adverse effects were noted. In addition, Chauan et al also noted good pain control&#xD;
      with intracervical injection with lidocaine in patients undergoing a hysterosalpingography,&#xD;
      which involves distended the uterus and injecting dye. Mankowshi et al also studied both&#xD;
      intracervical and paracervical injections of lidocaine for first trimester suction curettage&#xD;
      and found no difference between the two forms ensuring that both effective means of&#xD;
      analgesia.&#xD;
&#xD;
      In the U.S., surgical site infections (SSI) affect 1 in 24 patients that undergo inpatient&#xD;
      surgery. Most surgical site infection take place after day 5 , which will be out of the scope&#xD;
      of timeframe for conduct of the survey. However a SSI can make the differentiation of pain&#xD;
      from the surgery itself and pain from a complication of surgery difficulty to differentiate.&#xD;
      The patient will be asked to specify where the pain is and ask if they have any associated&#xD;
      vaginal discharge, foul smelling odor, and difficulty urinating and or passing a bowel&#xD;
      movement. These responses will be tracked, and if the participant shows signs of a SSI, the&#xD;
      patients may warrant a closer followup in the office and or asked to go directly to the&#xD;
      Emergency Department (ED). The patients will still be included in the study but special note&#xD;
      will be made of how many participant had SSI in the discussion portion.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      Randomized double blind placebo controlled pilot study. After IRB approval, 52 subjects will&#xD;
      be consented to participate in the study. The study includes subjects undergoing minimally&#xD;
      invasive (robot--assisted or traditional laparoscopy) supracervical hysterectomy under&#xD;
      general anesthesia. This study will include women (35 - 75 years) who have American Congress&#xD;
      of Obstetricians and Gynecologists (ACOG) and American Association of Gynecologic&#xD;
      Laparoscopists (AAGL) physical classification status for a minimally invasive (robotic-&#xD;
      assisted or traditional laparoscopy)supracervical hysterectomy.&#xD;
&#xD;
      Randomization will be done prior to recruitment of patient via computer software. There will&#xD;
      be two groups with numbers 1-52, no numbers will be repeated. Each patient that is recruited&#xD;
      will be assigned a number from 1-52 (in sequential order); the master list will be kept with&#xD;
      the pharmacy director. Group A (control, n=26) to receive 20ml of saline while Group B&#xD;
      (study, n=26) to receive 20ml of liposomal bupivacaine (EXPAREL) into the stroma of the&#xD;
      cervix at the 4 and 8 o'clock positions (innervation insertion points of the cervix).&#xD;
&#xD;
      The MMC Pharmacy will prepare an individualized numbered bubble wrapped amber package&#xD;
      accordingly to the randomization. It will be prepared prior to the recruitment and kept in&#xD;
      the fridge in 4th floor PACU pharmacy. After the patient is consented and given a subject&#xD;
      number, the package with the corresponding number will be picked up from the pharmacy and&#xD;
      given to either the resident/attending (not involved in the study) who will share the&#xD;
      contents of the package with the anesthesia team. While prepping, the same individual will&#xD;
      inject the contents. The syringe will covered as to disguise the contents of the syringe.&#xD;
&#xD;
      The investigators will show a short video on how to prepare the Exparel as well the injection&#xD;
      component in order to diminish the differences between the individuals.&#xD;
&#xD;
      Measurements:&#xD;
&#xD;
      The severity of pain will be assessed preoperatively in the holding area, PACU arrival, 12,&#xD;
      24, and 48 hours postoperatively using a numeric rating scale (NRS) at rest for pain with 0 =&#xD;
      no pain and 10 = worst possible pain. Pain inquiries will assess low pelvic/suprapubic area&#xD;
      and lower abdominal pain, type of pain (dull, achy, sharp, stabbing, etc.) and radiation of&#xD;
      pain to a surrounding area. Other endpoints will include number of patients who required&#xD;
      break through (additional) opioid analgesic medications, median time to first break through&#xD;
      opioid use, total opioid analgesic requirement. The time, day and number of requests for&#xD;
      break through (additional) analgesia will be noted by gynecologic surgery team (Resident or&#xD;
      Fellow) participating in this study.&#xD;
&#xD;
      When the patient is home the patient will have a Pain Medication Diary that the investigators&#xD;
      will provide for the patient prior to discharge. The patient will bring at the post-operative&#xD;
      visit and or mail it in.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2019</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain at 12 hours</measure>
    <time_frame>12 hours after surgery</time_frame>
    <description>Participant will be shown a card that has a visual analogue (Faces) pains scale combined with numerical (0-10) analogue scale (0 is no pain, 10 is the worst pain imaginable).at 12 hours postoperatively</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain at 24 hours</measure>
    <time_frame>24 hours after surgey</time_frame>
    <description>Participant will be shown a card that has a visual analogue (Faces) pains scale combined with numerical (0-10) analogue scale (0 is no pain, 10 is the worst pain imaginable).at 24 hours postoperatively</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Painat 48 hours</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>Participant will be shown a card that has a visual analogue (Faces) pains scale combined with numerical (0-10) analogue scale (0 is no pain, 10 is the worst pain imaginable) at 48 hours postoperatively</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patients with additional pain medications</measure>
    <time_frame>48 hours</time_frame>
    <description>Number of patients who required additional pain medications</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Saline Solution for Injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A (control, n=26) to receive 20ml of saline while prepping. The syringe will covered as to disguise the contents of the syringe.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exparel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group B (study, n=26) to receive 20ml of liposomal bupivacaine (EXPAREL) into the stroma of the cervix at the 4 and 8 o'clock positions (innervation insertion points of the cervix).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline Solution for Injection</intervention_name>
    <description>Injection of 20mL of 0.9%Normal Saline</description>
    <arm_group_label>Saline Solution for Injection</arm_group_label>
    <other_name>Standard</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exparel</intervention_name>
    <description>Exparel (bupivacaine liposome injectable suspension) is a liposome injection of bupivacaine, an amide-type local anesthetic, indicated (bupivacaine liposome injectable suspension) for administration into the surgical site to produce postsurgical analgesia.</description>
    <arm_group_label>Exparel</arm_group_label>
    <other_name>liposomal bupivicaine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 35--75 years of age at the Screening Visit.&#xD;
&#xD;
          2. Female subjects only.&#xD;
&#xD;
          3. Scheduled to undergo minimally invasive (robotic-assisted or laparoscopic)&#xD;
             supracervical hysterectomy, under general anesthesia.&#xD;
&#xD;
          4. Clinical laboratory values less than twice the upper limit of normal or, if abnormal,&#xD;
             deemed not clinically significant per the Investigator.&#xD;
&#xD;
          5. Ability to provide informed consent, adhere to the study visit schedule and complete&#xD;
             all study assessments and language specific questionnaires.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently pregnant, nursing, or planning to become pregnant.&#xD;
&#xD;
          2. Use of any of the following medications within the times specified before surgery: a.&#xD;
             opioid, SSRI, tricyclic antidepressant, gabapentin, pregabalin within three days of&#xD;
             surgery. b. Use of acetaminophen within 24 hours of surgery.&#xD;
&#xD;
          3. Concurrent painful physical condition or concurrent surgery that may require analgesic&#xD;
             treatment (such as NSAID, opioid, SSRI, tricyclic antidepressant, gabapentin,&#xD;
             pregabalin) in the postoperative period for pain that is not strictly related to the&#xD;
             minimally invasive supracervical hysterectomy procedure and may confound the&#xD;
             postoperative assessments (e.g., rheumatoid arthritis, chronic neuropathic pain.&#xD;
&#xD;
          4. Chronic user of analgesic medications, including taking opioid medications for more&#xD;
             than 14 days in the last 3 months, or non-opioid pain medications more than 5 times&#xD;
             per week.&#xD;
&#xD;
          5. Current use of systemic glucocorticosteroids (e.g. Decadron) or use of glucocorticoids&#xD;
             within one month of enrollment into this study.&#xD;
&#xD;
          6. History of hepatitis (other than hepatitis A).&#xD;
&#xD;
          7. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription&#xD;
             medicine(s), or alcohol within the past 2 years.&#xD;
&#xD;
          8. Failure of presurgical drug and alcohol screen.&#xD;
&#xD;
          9. History of hypersensitivity or idiosyncratic reactions to amide-type local&#xD;
             anesthetics, opioids, or propofol.&#xD;
&#xD;
         10. Administration of an investigational drug within 30 days prior to study drug&#xD;
             administration, or planned administration of another investigational product or&#xD;
             procedure during the subject's participation in this study.&#xD;
&#xD;
        12. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion&#xD;
        of the Investigator, may interfere with study assessments or compliance. 13. Significant&#xD;
        medical conditions or laboratory results that, in the opinion of the Investigator indicate&#xD;
        an increased vulnerability to study drug and procedures, and expose subjects to an&#xD;
        unreasonable risk as a result of participating in this clinical trial. 14. Any clinically&#xD;
        significant event or condition uncovered during the surgery (e.g., excessive bleeding,&#xD;
        acute sepsis) that might render the subject medically unstable or complicate the subject's&#xD;
        postoperative course. 15. An incision length greater than 3 cm.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pedram Bral, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Minimally Invasive Surgery -Fellowship Director</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mary Ann H Son, M.D.</last_name>
    <phone>6465263287</phone>
    <email>sonmaryann@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Camilla Paiva, M.D.</last_name>
    <phone>954 496 1275</phone>
    <email>Cpaiva@maimonidesmed.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Maimonides Medical Center</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11219</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mary Ann Son, MD</last_name>
      <email>mson@maimonidesmed.org</email>
    </contact>
    <contact_backup>
      <last_name>Pedram Bral, MD</last_name>
      <email>pbral@maimonidesmed.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011 Dec;54(12):1552-9. doi: 10.1097/DCR.0b013e318232d4c1.</citation>
    <PMID>22067185</PMID>
  </results_reference>
  <results_reference>
    <citation>White PF. Multimodal analgesia: its role in preventing postoperative pain. Curr Opin Investig Drugs. 2008 Jan;9(1):76-82.</citation>
    <PMID>18183534</PMID>
  </results_reference>
  <results_reference>
    <citation>Smoot JD, Bergese SD, Onel E, Williams HT, Hedden W. The efficacy and safety of DepoFoam bupivacaine in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty: a randomized, double-blind, active-control study. Aesthet Surg J. 2012 Jan;32(1):69-76. doi: 10.1177/1090820X11430831. Epub 2011 Dec 16.</citation>
    <PMID>22179931</PMID>
  </results_reference>
  <results_reference>
    <citation>Portillo J, Kamar N, Melibary S, Quevedo E, Bergese S. Safety of liposome extended-release bupivacaine for postoperative pain control. Front Pharmacol. 2014 Apr 30;5:90. doi: 10.3389/fphar.2014.00090. eCollection 2014.</citation>
    <PMID>24817851</PMID>
  </results_reference>
  <results_reference>
    <citation>Chudnoff S, Einstein M, Levie M. Paracervical block efficacy in office hysteroscopic sterilization: a randomized controlled trial. Obstet Gynecol. 2010 Jan;115(1):26-34. doi: 10.1097/AOG.0b013e3181c51ace.</citation>
    <PMID>20027030</PMID>
  </results_reference>
  <results_reference>
    <citation>Lukes AS, Roy KH, Presthus JB, Diamond MP, Berman JM, Konsker KA. Randomized comparative trial of cervical block protocols for pain management during hysteroscopic removal of polyps and myomas. Int J Womens Health. 2015 Oct 13;7:833-9. doi: 10.2147/IJWH.S50101. eCollection 2015. Erratum In: Int J Womens Health. 2015;7:871.</citation>
    <PMID>26543383</PMID>
  </results_reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>August 22, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>December 6, 2018</last_update_submitted>
  <last_update_submitted_qc>December 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Maimonides Medical Center</investigator_affiliation>
    <investigator_full_name>Pedram Bral</investigator_full_name>
    <investigator_title>Minimally Invasive Surgery Program Director</investigator_title>
  </responsible_party>
  <keyword>laparoscopy</keyword>
  <keyword>supracervical hysterectomy</keyword>
  <keyword>Multimodal pain management</keyword>
  <keyword>bupivacaine liposome</keyword>
  <keyword>Exparel</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>December 11, 2019</submitted>
    <returned>December 26, 2019</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03769714
org study id: 2018-02-12-MMC
nct id: NCT03769714
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The aim of the of the study is a reduction in minimally invasive supracervical hysterectomy
      postsurgical pain, which may result in less need for supplemental opioid pain medications,
      fewer opioid related adverse events, and a better recovery experience for patients, which may
      offer an economic benefit to health care systems.

      Intracervical preoperative dose of Exparel during minimally invasive (robotic--assisted or
      traditional laparoscopy) supracervical hysterectomy reduces cumulative pain scores for up to
      24 hours and reduces overall requests for break through (additional) analgesia with opioid
      consumption compared with placebo.
Exparel is a local analgesic that utilizes bupivacaine in combination with the proven product
      delivery platform, DepoFoam®. Exparel (bupivacaine liposome injectable suspension) is a
      liposome injection of bupivacaine, an amide-type local anesthetic, indicated (bupivacaine
      liposome injectable suspension) for administration into the surgical site to produce
      postsurgical analgesia. Liposomal drug- containing formulations can provide for controlled
      drug release over an extended period of time.

      The overall length of hospital stay (LOS) for patients undergoing laparoscopic (robot-
      assisted or traditional laparoscopy) supracervical hysterectomy varies widely in published
      reports; typical durations range between 0 days and 4 days.

      That is because in recent years there has been a trend toward use of enhanced or "fast-
      track" discharge protocols to reduce LOS in patients undergoing this procedure, predicated
      primarily on reducing the time to achieve tolerance of oral liquid/food intake and improved
      GI function. Most patients experience moderate to extreme pain after surgery and effective
      postsurgical pain management is a key factor affecting patient recovery. Multimodal analgesia
      techniques involving analgesics, such as local anesthetics, oral or parenteral nonsteroidal
      anti-inflammatory medications, and oral or parenteral opioids, are recommended as the safest
      and effective approach to postsurgical pain control. Local anesthetics administered during
      surgery are frequently used as part of multimodal analgesic regimens; however, the duration
      of analgesia with these agents is short (12 hours). Bupivacaine has a long history of use in
      the surgical setting, and the efficacy of bupivacaine HCl administered perioperatively via
      wound infiltration or acute postsurgical pain is well established. A novel formulation of
      bupivacaine, ie, liposome bupivacaine (Pacira Pharmaceuticals, Inc., Parsippany, NJ), has
      been developed to address the need for longer-acting local anesthetics that can be
      administered as a single dose. The question becomes whether this drug is effective for
      postsurgical analgesia if given preoperatively via the intracervical stroma during minimally
      invasive gynecologic surgical procedures, specifically laparoscopic (robot--assisted or
      traditional laparoscopy) supracervical hysterectomy.

      Paracervical/intracervical injections are used for cervical/uterine manipulation in various
      obstetrical and gynecological procedures. Lukas et al used the intracervical/paracervical
      block prior to hysteroscopic polypectomy, with good pain scores following the procedure and
      no serious adverse effects were noted. In addition, Chauan et al also noted good pain control
      with intracervical injection with lidocaine in patients undergoing a hysterosalpingography,
      which involves distended the uterus and injecting dye. Mankowshi et al also studied both
      intracervical and paracervical injections of lidocaine for first trimester suction curettage
      and found no difference between the two forms ensuring that both effective means of
      analgesia.

      In the U.S., surgical site infections (SSI) affect 1 in 24 patients that undergo inpatient
      surgery. Most surgical site infection take place after day 5 , which will be out of the scope
      of timeframe for conduct of the survey. However a SSI can make the differentiation of pain
      from the surgery itself and pain from a complication of surgery difficulty to differentiate.
      The patient will be asked to specify where the pain is and ask if they have any associated
      vaginal discharge, foul smelling odor, and difficulty urinating and or passing a bowel
      movement. These responses will be tracked, and if the participant shows signs of a SSI, the
      patients may warrant a closer followup in the office and or asked to go directly to the
      Emergency Department (ED). The patients will still be included in the study but special note
      will be made of how many participant had SSI in the discussion portion.

      Methods:

      Randomized double blind placebo controlled pilot study. After IRB approval, 52 subjects will
      be consented to participate in the study. The study includes subjects undergoing minimally
      invasive (robot--assisted or traditional laparoscopy) supracervical hysterectomy under
      general anesthesia. This study will include women (35 - 75 years) who have American Congress
      of Obstetricians and Gynecologists (ACOG) and American Association of Gynecologic
      Laparoscopists (AAGL) physical classification status for a minimally invasive (robotic-
      assisted or traditional laparoscopy)supracervical hysterectomy.

      Randomization will be done prior to recruitment of patient via computer software. There will
      be two groups with numbers 1-52, no numbers will be repeated. Each patient that is recruited
      will be assigned a number from 1-52 (in sequential order); the master list will be kept with
      the pharmacy director. Group A (control, n=26) to receive 20ml of saline while Group B
      (study, n=26) to receive 20ml of liposomal bupivacaine (EXPAREL) into the stroma of the
      cervix at the 4 and 8 o'clock positions (innervation insertion points of the cervix).

      The MMC Pharmacy will prepare an individualized numbered bubble wrapped amber package
      accordingly to the randomization. It will be prepared prior to the recruitment and kept in
      the fridge in 4th floor PACU pharmacy. After the patient is consented and given a subject
      number, the package with the corresponding number will be picked up from the pharmacy and
      given to either the resident/attending (not involved in the study) who will share the
      contents of the package with the anesthesia team. While prepping, the same individual will
      inject the contents. The syringe will covered as to disguise the contents of the syringe.

      The investigators will show a short video on how to prepare the Exparel as well the injection
      component in order to diminish the differences between the individuals.

      Measurements:

      The severity of pain will be assessed preoperatively in the holding area, PACU arrival, 12,
      24, and 48 hours postoperatively using a numeric rating scale (NRS) at rest for pain with 0 =
      no pain and 10 = worst possible pain. Pain inquiries will assess low pelvic/suprapubic area
      and lower abdominal pain, type of pain (dull, achy, sharp, stabbing, etc.) and radiation of
      pain to a surrounding area. Other endpoints will include number of patients who required
      break through (additional) opioid analgesic medications, median time to first break through
      opioid use, total opioid analgesic requirement. The time, day and number of requests for
      break through (additional) analgesia will be noted by gynecologic surgery team (Resident or
      Fellow) participating in this study.

      When the patient is home the patient will have a Pain Medication Diary that the investigators
      will provide for the patient prior to discharge. The patient will bring at the post-operative
      visit and or mail it in.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pain at 12 hours
time frame: 12 hours after surgery
description: Participant will be shown a card that has a visual analogue (Faces) pains scale combined with numerical (0-10) analogue scale (0 is no pain, 10 is the worst pain imaginable).at 12 hours postoperatively
measure: Pain at 24 hours
time frame: 24 hours after surgey
description: Participant will be shown a card that has a visual analogue (Faces) pains scale combined with numerical (0-10) analogue scale (0 is no pain, 10 is the worst pain imaginable).at 24 hours postoperatively
measure: Painat 48 hours
time frame: 48 hours after surgery
description: Participant will be shown a card that has a visual analogue (Faces) pains scale combined with numerical (0-10) analogue scale (0 is no pain, 10 is the worst pain imaginable) at 48 hours postoperatively
measure: Patients with additional pain medications
time frame: 48 hours
description: Number of patients who required additional pain medications
arm group label: Saline Solution for Injection
arm group type: Active Comparator
description: Group A (control, n=26) to receive 20ml of saline while prepping. The syringe will covered as to disguise the contents of the syringe.
arm group label: Exparel
arm group type: Experimental
description: Group B (study, n=26) to receive 20ml of liposomal bupivacaine (EXPAREL) into the stroma of the cervix at the 4 and 8 o'clock positions (innervation insertion points of the cervix).
intervention type: Drug
intervention name: Saline Solution for Injection
description: Injection of 20mL of 0.9%Normal Saline
arm group label: Saline Solution for Injection
other name: Standard
intervention type: Drug
intervention name: Exparel
description: Exparel (bupivacaine liposome injectable suspension) is a liposome injection of bupivacaine, an amide-type local anesthetic, indicated (bupivacaine liposome injectable suspension) for administration into the surgical site to produce postsurgical analgesia.
arm group label: Exparel
other name: liposomal bupivicaine
criteria: 
gender: Female
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pedram Bral, M.D.
role: Principal Investigator
affiliation: Minimally Invasive Surgery -Fellowship Director
last name: Mary Ann H Son, M.D.
phone: 6465263287
email: sonmaryann@gmail.com
last name: Camilla Paiva, M.D.
phone: 954 496 1275
email: Cpaiva@maimonidesmed.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011 Dec;54(12):1552-9. doi: 10.1097/DCR.0b013e318232d4c1.
PMID: 22067185
citation: White PF. Multimodal analgesia: its role in preventing postoperative pain. Curr Opin Investig Drugs. 2008 Jan;9(1):76-82.
PMID: 18183534
citation: Smoot JD, Bergese SD, Onel E, Williams HT, Hedden W. The efficacy and safety of DepoFoam bupivacaine in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty: a randomized, double-blind, active-control study. Aesthet Surg J. 2012 Jan;32(1):69-76. doi: 10.1177/1090820X11430831. Epub 2011 Dec 16.
PMID: 22179931
citation: Portillo J, Kamar N, Melibary S, Quevedo E, Bergese S. Safety of liposome extended-release bupivacaine for postoperative pain control. Front Pharmacol. 2014 Apr 30;5:90. doi: 10.3389/fphar.2014.00090. eCollection 2014.
PMID: 24817851
citation: Chudnoff S, Einstein M, Levie M. Paracervical block efficacy in office hysteroscopic sterilization: a randomized controlled trial. Obstet Gynecol. 2010 Jan;115(1):26-34. doi: 10.1097/AOG.0b013e3181c51ace.
PMID: 20027030
citation: Lukes AS, Roy KH, Presthus JB, Diamond MP, Berman JM, Konsker KA. Randomized comparative trial of cervical block protocols for pain management during hysteroscopic removal of polyps and myomas. Int J Womens Health. 2015 Oct 13;7:833-9. doi: 10.2147/IJWH.S50101. eCollection 2015. Erratum In: Int J Womens Health. 2015;7:871.
PMID: 26543383
responsible party type: Principal Investigator
investigator affiliation: Maimonides Medical Center
investigator full name: Pedram Bral
investigator title: Minimally Invasive Surgery Program Director
mesh term: Bupivacaine
submitted: December 11, 2019
returned: December 26, 2019