<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/NCT04415931</url>
  </required_header>
  <id_info>
    <org_study_id>2022248</org_study_id>
    <nct_id>NCT04415931</nct_id>
  </id_info>
  <brief_title>Local Infiltration Analgesia Vs. Interscalene Block in Total Shoulder Arthorplasty</brief_title>
  <official_title>Local Infiltration Analgesia Vs. Interscalene Block in Total Shoulder Arthorplasty: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</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>
      Pain management following total shoulder arthroplasty is an important factor in determining&#xD;
      patient outcomes and satisfaction. Interscalene brachial plexus blockade has been used&#xD;
      successfully to minimize pain in the acute post-operative period. While shown to be&#xD;
      effective, interscalene blockade has known complications. In addition, interscalene block has&#xD;
      been shown to be significantly more expensive when compared to local anesthesia infiltration.&#xD;
&#xD;
      Local anesthetics such as bupivacaine have long been used to assist in post-operative&#xD;
      anesthesia. Recent reports have demonstrated local infiltration of liposomal bupivacaine to&#xD;
      be similar to interscalene block in regards to patient analgesia even in the first 24 hours&#xD;
      post operatively, with the added benefit of lower complications and costs. While most reports&#xD;
      examine the efficacy of local infiltration with liposomal bupivacaine in the shoulder, other&#xD;
      total joint literature has been positive regarding the use of local infiltration analgesic&#xD;
      mixture for improved post-operative analgesia using a multi-modal approach to infiltrative&#xD;
      analgesia. Despite these reports, the role and efficacy of local infiltration analgesia in&#xD;
      shoulder arthroplasty is lacking. The purpose of the proposed study is to determine the&#xD;
      efficacy and safety of local infiltration analgesia in shoulder arthroplasty in comparison to&#xD;
      interscalene block through a randomized prospective clinical trial. Our hypothesis is that&#xD;
      local infiltration analgesia will lead to postoperative pain scores, opiate consumption, and&#xD;
      complication rate that are not significantly different from interscalene block.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. SELECTION OF SUBJECTS • Inclusion Criteria: Adult patients (18 years of age or greater)&#xD;
           undergoing primary anatomic or reverse total shoulder arthroplasty secondary to&#xD;
           osteoarthritis, cuff tear arthropathy, or massive irreparable rotator cuff tear.&#xD;
&#xD;
           • Exclusion Criteria :&#xD;
&#xD;
             -  Narcotic dependent&#xD;
&#xD;
             -  Previous ipsilateral open shoulder surgery&#xD;
&#xD;
             -  Chronic pain syndromes (fibromyalgia)&#xD;
&#xD;
             -  Contraindication to regional anesthesia&#xD;
&#xD;
             -  Cervical radiculopathy&#xD;
&#xD;
             -  Unable to give consent; Prisoner&#xD;
&#xD;
             -  Workers compensation insurance&#xD;
&#xD;
             -  Mentally Disabled.&#xD;
&#xD;
             -  Pregnant Patients&#xD;
&#xD;
        2. STUDY PROCEDURE • Timeline: 2 weeks of data collection&#xD;
&#xD;
           • Study subjects: Study candidates will be identified as they present to the clinic at&#xD;
           the Missouri Orthopaedic Institute at the University of Missouri, and will be evaluated&#xD;
           by the principle investigator. Informed consent will be obtained as per IRB protocol.&#xD;
           Enrollees will receive a copy of the study protocol, consent, and HIPAA form. Background&#xD;
           patient information will be collected including age, sex, BMI and co-morbidities.&#xD;
           American Society of Anesthesiologist (ASA) classification will be assigned by the&#xD;
           involved anesthesiologist.&#xD;
&#xD;
           Interscalene regional block is routinely administered at our institution prior to total&#xD;
           shoulder arthroplasty. Patients will be randomized prior to their scheduled surgery date&#xD;
           by our research team using a randomization protocol developed by our department&#xD;
           biostatistics team. The surgeon and surgical assistants will be blinded about the group&#xD;
           assignment until the morning of the surgery day. The group assignment will be sealed in&#xD;
           an envelope and delivered to the surgeon. If randomized to the interscalene block group,&#xD;
           the anesthesia team will administer the block preoperatively in routine fashion. The&#xD;
           standard anesthesia protocol for total shoulder arthroplasty patients is as follows:&#xD;
&#xD;
           • Preoperative: Acetaminophen 1000mg PO Gabapentin 300mg PO Interscalene block: 3-5mL of&#xD;
           0.5% bupivacaine plus 10mL Exparel (1-2 mg of midazolam and/or 50-100 mcg of fentanyl IV&#xD;
           for sedation)&#xD;
&#xD;
           If randomized to local infiltration analgesia, the patient will receive local&#xD;
           infiltration injection intraoperatively prior to closing during the procedure. A&#xD;
           standardized dose of 100 mL of infiltration will be utilized according to the following&#xD;
           formula. The mixture will be injected into the deltoid and pectoralis major muscles and&#xD;
           fasciae, and subcutaneous tissues using an 18-guage needle.&#xD;
&#xD;
           Total dose 100mL Ropivacaine 0.5% 40mL Epinephrine 1mg/mL 0.1mL Ketorolac 30mg/mL 1mL&#xD;
           Morphine 10mg/mL 0.5mL Normal saline 0.9% 58.4mL&#xD;
&#xD;
             -  Anesthesia protocol All surgery will be performed with standard general anesthesia.&#xD;
                Induction will be achieved and general anesthesia maintained based on the following&#xD;
                protocol&#xD;
&#xD;
           (Doses vary based on patient specifics such as age, weight and comorbid disease):&#xD;
           Lidocaine 50 - 100mg Fentanyl 50 - 100mcg Propofol 100 - 200 mg Rocuronium 50 - 100mg&#xD;
&#xD;
             -  Intraoperative:&#xD;
&#xD;
           Sevoflurane 1 - 2% or desflurane 4 - 6% Fentanyl, hydromorphone, ketorolac and / or&#xD;
           ketamine IV as needed on suspicion of pain.&#xD;
&#xD;
           antibiotics were given intravenously 2g of cefazolin or 900mg of clindamycin.&#xD;
&#xD;
             -  Surgical procedure All surgery will be performed in beach chair position by a&#xD;
                single shoulder and elbow fellowship trained surgeon. A standard deltopectoral&#xD;
                approach will be used. A subscapularis peel-off will be used for all anatomic total&#xD;
                shoulder arthroplasty cases and repaired back to the lesser tuberosity with&#xD;
                transosseous sutures. For reverse shoulder arthroplasty cases, the subscapularis&#xD;
                will be repaired if there is a reparable subscapularis tendon. Following the&#xD;
                surgery, the shoulder will be immobilized in an abduction pillow-sling. A mixture&#xD;
                of 1g of tranexamic acid and 30mL of normal saline will be poured into the wound&#xD;
                for postoperative bleeding control purposes. Patients will follow the routine&#xD;
                postoperative rehabilitation protocols. Patients will return to the shoulder and&#xD;
                elbow clinic for routine clinical follow-up visits and x-ray exams following their&#xD;
                surgery at 2 weeks, 6 weeks, 12 weeks, and 6 months, which is the standard of care.&#xD;
                The study data collection will be completed at 2 week time point when the patient&#xD;
                comes back for their first postoperative appointment.&#xD;
&#xD;
             -  Data collection: Following surgery, the patient's pain level will be recorded in a&#xD;
                visual analog scale (VAS) at 4, 8, 12, 24 hours, once a day for the following 6&#xD;
                days, and at 14 days following surgery. Patient's daily opiate consumption during&#xD;
                the first 7 days and the total cumulative amount of consumption up to 14 days&#xD;
                following surgery will also be recorded, quantified and converted to morphine&#xD;
                equivalents units (MEU) for standardization. Time to discharge from PACU as well as&#xD;
                adverse opioid reactions will be reported (nausea, hypoxia/O2 requirement). The&#xD;
                inpatient portion of the pain VAS and opiate consumption data will be obtained from&#xD;
                the medical record while the post-discharge part of the data will be collected via&#xD;
                a physical log given to patients upon discharge as well as an automated&#xD;
                patient-reported outcome data collection system (PatientIQ®, Chicago, IL, USA). The&#xD;
                research team will contact patients every other day following discharge to ensure&#xD;
                proper documentation of pain VAS and opiate consumption by patients. Additionally,&#xD;
                data regarding the time in the operating room, length of hospital stay,&#xD;
                intraoperative complications (fracture, vascular injury, and anesthesia-related),&#xD;
                acute postoperative complications (medical, nerve injury, dislocation, hematoma,&#xD;
                and wound complications) will be collected. The average costs of LIA and&#xD;
                interscalene regional block will be obtained through our billing department.&#xD;
&#xD;
           Data analysis The pain score and opiate consumption data at each time point will be&#xD;
           compared between the two groups using either unpaired t-test or Mann-Whitney U test&#xD;
           depending on the data normality. The chronological changes in the pain score and opiate&#xD;
           consumption in each patient will be analyzed using repeated measures ANOVA or Friedman&#xD;
           test depending on the data normality. Categorical variables will be compared using&#xD;
           chi-square test or Fisher's Exact test. The data will be analyzed by our biostatistics&#xD;
           team within Department of Orthopaedic Surgery. The primary outcome of the study is the&#xD;
           average pain VAS scores during the first 12 hours following surgery. The secondary&#xD;
           outcome is the opioid consumption during the first 2 days following surgery.&#xD;
           Non-inferiority of the local infiltration group compared to the interscalene block group&#xD;
           in these two outcomes will be tested using a non-inferiority test.&#xD;
&#xD;
           • Sample size calculation and power: The primary outcome of the study is the average&#xD;
           pain VAS scores during the first 12 hours following surgery. Based on the recent&#xD;
           research finding that a 1.4-point difference in pain VAS scores is a minimally&#xD;
           clinically important difference (MCID) following shoulder arthroplasty, a priori sample&#xD;
           size calculation was performed with a power of 0.8 and a standard deviation of 2.4 at an&#xD;
           alpha of 0.05 to examine the study hypothesis that the average pain VAS score during the&#xD;
           first 12 hours in the local infiltration analgesia group would not be significantly&#xD;
           different than that of the interscalene block group (or the difference between the two&#xD;
           groups would be less than 1.5 points). The result showed a minimum of 37 patients would&#xD;
           be needed in each group (total number of patients =74).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 15, 2020</start_date>
  <completion_date type="Actual">March 13, 2022</completion_date>
  <primary_completion_date type="Actual">March 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Patients will be randomized prior to their scheduled surgery date by our research team using a randomization protocol developed by our department biostatistics team. The surgeons and anesthesiologists will be blinded about the group assignment until the day before surgery. The group assignment will be sealed in an envelope and delivered to the surgeon.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pain visual analog scale (VAS)</measure>
    <time_frame>From 4 hours to 14 days postop</time_frame>
    <description>Following surgery, the patient's pain level will be recorded in a visual analog scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, 2 days and daily until 7 days, and then at 14 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Opiate consumption</measure>
    <time_frame>From postop day 1 to 2 weeks</time_frame>
    <description>The patient's daily opiate consumption during the first 7 days following surgery and the toal accumulated amount of opiate consumption by 2 weeks postop will also be recorded, quantified and converted to morphine equivalents units (MEU) for standardization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>for postoperative 1 week</time_frame>
    <description>Length of hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative complications</measure>
    <time_frame>for postoperative 3 months</time_frame>
    <description>Postoperative complications (medical, nerve injury, dislocation, hematoma, and wound complications)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative complications</measure>
    <time_frame>Intraoperative</time_frame>
    <description>Intraoperative complications (fracture, vascular injury, and anesthesia-related),</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of surgical procedure</measure>
    <time_frame>Intraoperative</time_frame>
    <description>Length of surgical procedure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Shoulder Osteoarthritis</condition>
  <condition>Cuff Tear Arthropathy</condition>
  <condition>Massive Rotator Cuff Tear</condition>
  <arm_group>
    <arm_group_label>Local infiltration analgesia group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group of patients will receive local infiltration analgesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Interscalene block group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This group of patients will receive interscalene block</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Local infiltration analgesia</intervention_name>
    <description>Local infiltration injection intraoperatively prior to closing during the procedure. A standardized dose of 100 mL of infiltration will be utilized according to the following formula. The mixture will be injected into the deltoid and pectoralis major muscles and fasciae, and subcutaneous tissues using an 18-guage needle.&#xD;
Total dose 100mL&#xD;
Ropivacaine 0.5% 40mL Epinephrine 1mg/mL 0.1mL Ketorolac 30mg/mL 1mL Morphine 10mg/mL 0.5mL Normal saline 0.9% 58.4mL</description>
    <arm_group_label>Local infiltration analgesia group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Interscalene block</intervention_name>
    <description>Standard interscalene brachial plexus regional block</description>
    <arm_group_label>Interscalene block group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (18 years of age or greater)&#xD;
&#xD;
          -  Primary anatomic or reverse total shoulder arthroplasty secondary to osteoarthritis,&#xD;
             cuff tear arthropathy, or massive irreparable rotator cuff tear&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Narcotic dependent&#xD;
&#xD;
          -  Previous ipsilateral open shoulder surgery&#xD;
&#xD;
          -  Chronic pain syndromes (fibromyalgia)&#xD;
&#xD;
          -  Contraindication to regional anesthesia&#xD;
&#xD;
          -  Cervical radiculopathy&#xD;
&#xD;
          -  Workers compensation insurance&#xD;
&#xD;
          -  Mentally Disabled.&#xD;
&#xD;
          -  Pregnant Patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Missouri</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Menendez ME, Lawler SM, Ring D, Jawa A. High pain intensity after total shoulder arthroplasty. J Shoulder Elbow Surg. 2018 Dec;27(12):2113-2119. doi: 10.1016/j.jse.2018.08.001. Epub 2018 Oct 12.</citation>
    <PMID>30322752</PMID>
  </results_reference>
  <results_reference>
    <citation>Bjornholdt KT, Jensen JM, Bendtsen TF, Soballe K, Nikolajsen L. Local infiltration analgesia versus continuous interscalene brachial plexus block for shoulder replacement pain: a randomized clinical trial. Eur J Orthop Surg Traumatol. 2015 Dec;25(8):1245-52. doi: 10.1007/s00590-015-1678-2. Epub 2015 Aug 15.</citation>
    <PMID>26276164</PMID>
  </results_reference>
  <results_reference>
    <citation>Namdari S, Nicholson T, Abboud J, Lazarus M, Steinberg D, Williams G. Interscalene Block with and without Intraoperative Local Infiltration with Liposomal Bupivacaine in Shoulder Arthroplasty: A Randomized Controlled Trial. J Bone Joint Surg Am. 2018 Aug 15;100(16):1373-1378. doi: 10.2106/JBJS.17.01416.</citation>
    <PMID>30106818</PMID>
  </results_reference>
  <results_reference>
    <citation>Namdari S, Nicholson T, Abboud J, Lazarus M, Steinberg D, Williams G. Randomized Controlled Trial of Interscalene Block Compared with Injectable Liposomal Bupivacaine in Shoulder Arthroplasty. J Bone Joint Surg Am. 2017 Apr 5;99(7):550-556. doi: 10.2106/JBJS.16.00296.</citation>
    <PMID>28375887</PMID>
  </results_reference>
  <results_reference>
    <citation>Okoroha KR, Lynch JR, Keller RA, Korona J, Amato C, Rill B, Kolowich PA, Muh SJ. Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty: a prospective randomized trial. J Shoulder Elbow Surg. 2016 Nov;25(11):1742-1748. doi: 10.1016/j.jse.2016.05.007. Epub 2016 Jul 14.</citation>
    <PMID>27422692</PMID>
  </results_reference>
  <results_reference>
    <citation>Sabesan VJ, Shahriar R, Petersen-Fitts GR, Whaley JD, Bou-Akl T, Sweet M, Milia M. A prospective randomized controlled trial to identify the optimal postoperative pain management in shoulder arthroplasty: liposomal bupivacaine versus continuous interscalene catheter. J Shoulder Elbow Surg. 2017 Oct;26(10):1810-1817. doi: 10.1016/j.jse.2017.06.044. Epub 2017 Aug 24.</citation>
    <PMID>28844420</PMID>
  </results_reference>
  <results_reference>
    <citation>Abdallah FW, Halpern SH, Aoyama K, Brull R. Will the Real Benefits of Single-Shot Interscalene Block Please Stand Up? A Systematic Review and Meta-Analysis. Anesth Analg. 2015 May;120(5):1114-1129. doi: 10.1213/ANE.0000000000000688.</citation>
    <PMID>25822923</PMID>
  </results_reference>
  <results_reference>
    <citation>Sicard J, Klouche S, Conso C, Billot N, Auregan JC, Poulain S, Lespagnol F, Solignac N, Bauer T, Ferrand M, Hardy P. Local infiltration analgesia versus interscalene nerve block for postoperative pain control after shoulder arthroplasty: a prospective, randomized, comparative noninferiority study involving 99 patients. J Shoulder Elbow Surg. 2019 Feb;28(2):212-219. doi: 10.1016/j.jse.2018.09.026. Epub 2018 Dec 10.</citation>
    <PMID>30545786</PMID>
  </results_reference>
  <results_reference>
    <citation>Weller WJ, Azzam MG, Smith RA, Azar FM, Throckmorton TW. Liposomal Bupivacaine Mixture Has Similar Pain Relief and Significantly Fewer Complications at Less Cost Compared to Indwelling Interscalene Catheter in Total Shoulder Arthroplasty. J Arthroplasty. 2017 Nov;32(11):3557-3562. doi: 10.1016/j.arth.2017.03.017. Epub 2017 Mar 16.</citation>
    <PMID>28390888</PMID>
  </results_reference>
  <results_reference>
    <citation>Andersen LO, Kehlet H. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty: a systematic review. Br J Anaesth. 2014 Sep;113(3):360-74. doi: 10.1093/bja/aeu155. Epub 2014 Jun 17.</citation>
    <PMID>24939863</PMID>
  </results_reference>
  <results_reference>
    <citation>Tashjian RZ, Hung M, Keener JD, Bowen RC, McAllister J, Chen W, Ebersole G, Granger EK, Chamberlain AM. Determining the minimal clinically important difference for the American Shoulder and Elbow Surgeons score, Simple Shoulder Test, and visual analog scale (VAS) measuring pain after shoulder arthroplasty. J Shoulder Elbow Surg. 2017 Jan;26(1):144-148. doi: 10.1016/j.jse.2016.06.007. Epub 2016 Aug 18.</citation>
    <PMID>27545048</PMID>
  </results_reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>March 10, 2023</last_update_submitted>
  <last_update_submitted_qc>March 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>H. Mike Kim</investigator_full_name>
    <investigator_title>ASSOCIATE PROFESSOR OF CLINICAL ORTHOPAEDIC SURGERY</investigator_title>
  </responsible_party>
  <keyword>Total Shoulder arthroplasty</keyword>
  <keyword>Reverse Shoulder arthroplasty</keyword>
  <keyword>Cuff tear arthropathy</keyword>
  <keyword>massive irreparable rotator cuff tear</keyword>
  <keyword>Anatomic total shoulder arthroplasty</keyword>
  <keyword>Shoulder osteoarthritis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Joint Diseases</mesh_term>
    <mesh_term>Rotator Cuff Tear Arthropathy</mesh_term>
    <mesh_term>Rotator Cuff Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data (IPD) will be shared with other members of the research team.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Data will be shared from actual study date until actual completion date</ipd_time_frame>
    <ipd_access_criteria>Treating relationship with a research team member listed on the IRB application.&#xD;
Research team members will work directly with providers that have a treating (patient-provider) relationship</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04415931
org study id: 2022248
nct id: NCT04415931
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Pain management following total shoulder arthroplasty is an important factor in determining
      patient outcomes and satisfaction. Interscalene brachial plexus blockade has been used
      successfully to minimize pain in the acute post-operative period. While shown to be
      effective, interscalene blockade has known complications. In addition, interscalene block has
      been shown to be significantly more expensive when compared to local anesthesia infiltration.

      Local anesthetics such as bupivacaine have long been used to assist in post-operative
      anesthesia. Recent reports have demonstrated local infiltration of liposomal bupivacaine to
      be similar to interscalene block in regards to patient analgesia even in the first 24 hours
      post operatively, with the added benefit of lower complications and costs. While most reports
      examine the efficacy of local infiltration with liposomal bupivacaine in the shoulder, other
      total joint literature has been positive regarding the use of local infiltration analgesic
      mixture for improved post-operative analgesia using a multi-modal approach to infiltrative
      analgesia. Despite these reports, the role and efficacy of local infiltration analgesia in
      shoulder arthroplasty is lacking. The purpose of the proposed study is to determine the
      efficacy and safety of local infiltration analgesia in shoulder arthroplasty in comparison to
      interscalene block through a randomized prospective clinical trial. Our hypothesis is that
      local infiltration analgesia will lead to postoperative pain scores, opiate consumption, and
      complication rate that are not significantly different from interscalene block.
1. SELECTION OF SUBJECTS • Inclusion Criteria: Adult patients (18 years of age or greater)
           undergoing primary anatomic or reverse total shoulder arthroplasty secondary to
           osteoarthritis, cuff tear arthropathy, or massive irreparable rotator cuff tear.

           • Exclusion Criteria :

             -  Narcotic dependent

             -  Previous ipsilateral open shoulder surgery

             -  Chronic pain syndromes (fibromyalgia)

             -  Contraindication to regional anesthesia

             -  Cervical radiculopathy

             -  Unable to give consent; Prisoner

             -  Workers compensation insurance

             -  Mentally Disabled.

             -  Pregnant Patients

        2. STUDY PROCEDURE • Timeline: 2 weeks of data collection

           • Study subjects: Study candidates will be identified as they present to the clinic at
           the Missouri Orthopaedic Institute at the University of Missouri, and will be evaluated
           by the principle investigator. Informed consent will be obtained as per IRB protocol.
           Enrollees will receive a copy of the study protocol, consent, and HIPAA form. Background
           patient information will be collected including age, sex, BMI and co-morbidities.
           American Society of Anesthesiologist (ASA) classification will be assigned by the
           involved anesthesiologist.

           Interscalene regional block is routinely administered at our institution prior to total
           shoulder arthroplasty. Patients will be randomized prior to their scheduled surgery date
           by our research team using a randomization protocol developed by our department
           biostatistics team. The surgeon and surgical assistants will be blinded about the group
           assignment until the morning of the surgery day. The group assignment will be sealed in
           an envelope and delivered to the surgeon. If randomized to the interscalene block group,
           the anesthesia team will administer the block preoperatively in routine fashion. The
           standard anesthesia protocol for total shoulder arthroplasty patients is as follows:

           • Preoperative: Acetaminophen 1000mg PO Gabapentin 300mg PO Interscalene block: 3-5mL of
           0.5% bupivacaine plus 10mL Exparel (1-2 mg of midazolam and/or 50-100 mcg of fentanyl IV
           for sedation)

           If randomized to local infiltration analgesia, the patient will receive local
           infiltration injection intraoperatively prior to closing during the procedure. A
           standardized dose of 100 mL of infiltration will be utilized according to the following
           formula. The mixture will be injected into the deltoid and pectoralis major muscles and
           fasciae, and subcutaneous tissues using an 18-guage needle.

           Total dose 100mL Ropivacaine 0.5% 40mL Epinephrine 1mg/mL 0.1mL Ketorolac 30mg/mL 1mL
           Morphine 10mg/mL 0.5mL Normal saline 0.9% 58.4mL

             -  Anesthesia protocol All surgery will be performed with standard general anesthesia.
                Induction will be achieved and general anesthesia maintained based on the following
                protocol

           (Doses vary based on patient specifics such as age, weight and comorbid disease):
           Lidocaine 50 - 100mg Fentanyl 50 - 100mcg Propofol 100 - 200 mg Rocuronium 50 - 100mg

             -  Intraoperative:

           Sevoflurane 1 - 2% or desflurane 4 - 6% Fentanyl, hydromorphone, ketorolac and / or
           ketamine IV as needed on suspicion of pain.

           antibiotics were given intravenously 2g of cefazolin or 900mg of clindamycin.

             -  Surgical procedure All surgery will be performed in beach chair position by a
                single shoulder and elbow fellowship trained surgeon. A standard deltopectoral
                approach will be used. A subscapularis peel-off will be used for all anatomic total
                shoulder arthroplasty cases and repaired back to the lesser tuberosity with
                transosseous sutures. For reverse shoulder arthroplasty cases, the subscapularis
                will be repaired if there is a reparable subscapularis tendon. Following the
                surgery, the shoulder will be immobilized in an abduction pillow-sling. A mixture
                of 1g of tranexamic acid and 30mL of normal saline will be poured into the wound
                for postoperative bleeding control purposes. Patients will follow the routine
                postoperative rehabilitation protocols. Patients will return to the shoulder and
                elbow clinic for routine clinical follow-up visits and x-ray exams following their
                surgery at 2 weeks, 6 weeks, 12 weeks, and 6 months, which is the standard of care.
                The study data collection will be completed at 2 week time point when the patient
                comes back for their first postoperative appointment.

             -  Data collection: Following surgery, the patient's pain level will be recorded in a
                visual analog scale (VAS) at 4, 8, 12, 24 hours, once a day for the following 6
                days, and at 14 days following surgery. Patient's daily opiate consumption during
                the first 7 days and the total cumulative amount of consumption up to 14 days
                following surgery will also be recorded, quantified and converted to morphine
                equivalents units (MEU) for standardization. Time to discharge from PACU as well as
                adverse opioid reactions will be reported (nausea, hypoxia/O2 requirement). The
                inpatient portion of the pain VAS and opiate consumption data will be obtained from
                the medical record while the post-discharge part of the data will be collected via
                a physical log given to patients upon discharge as well as an automated
                patient-reported outcome data collection system (PatientIQ®, Chicago, IL, USA). The
                research team will contact patients every other day following discharge to ensure
                proper documentation of pain VAS and opiate consumption by patients. Additionally,
                data regarding the time in the operating room, length of hospital stay,
                intraoperative complications (fracture, vascular injury, and anesthesia-related),
                acute postoperative complications (medical, nerve injury, dislocation, hematoma,
                and wound complications) will be collected. The average costs of LIA and
                interscalene regional block will be obtained through our billing department.

           Data analysis The pain score and opiate consumption data at each time point will be
           compared between the two groups using either unpaired t-test or Mann-Whitney U test
           depending on the data normality. The chronological changes in the pain score and opiate
           consumption in each patient will be analyzed using repeated measures ANOVA or Friedman
           test depending on the data normality. Categorical variables will be compared using
           chi-square test or Fisher's Exact test. The data will be analyzed by our biostatistics
           team within Department of Orthopaedic Surgery. The primary outcome of the study is the
           average pain VAS scores during the first 12 hours following surgery. The secondary
           outcome is the opioid consumption during the first 2 days following surgery.
           Non-inferiority of the local infiltration group compared to the interscalene block group
           in these two outcomes will be tested using a non-inferiority test.

           • Sample size calculation and power: The primary outcome of the study is the average
           pain VAS scores during the first 12 hours following surgery. Based on the recent
           research finding that a 1.4-point difference in pain VAS scores is a minimally
           clinically important difference (MCID) following shoulder arthroplasty, a priori sample
           size calculation was performed with a power of 0.8 and a standard deviation of 2.4 at an
           alpha of 0.05 to examine the study hypothesis that the average pain VAS score during the
           first 12 hours in the local infiltration analgesia group would not be significantly
           different than that of the interscalene block group (or the difference between the two
           groups would be less than 1.5 points). The result showed a minimum of 37 patients would
           be needed in each group (total number of patients =74).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Patients will be randomized prior to their scheduled surgery date by our research team using a randomization protocol developed by our department biostatistics team. The surgeons and anesthesiologists will be blinded about the group assignment until the day before surgery. The group assignment will be sealed in an envelope and delivered to the surgeon.
measure: Pain visual analog scale (VAS)
time frame: From 4 hours to 14 days postop
description: Following surgery, the patient's pain level will be recorded in a visual analog scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, 2 days and daily until 7 days, and then at 14 days.
measure: Opiate consumption
time frame: From postop day 1 to 2 weeks
description: The patient's daily opiate consumption during the first 7 days following surgery and the toal accumulated amount of opiate consumption by 2 weeks postop will also be recorded, quantified and converted to morphine equivalents units (MEU) for standardization
measure: Length of hospital stay
time frame: for postoperative 1 week
description: Length of hospital stay
measure: Postoperative complications
time frame: for postoperative 3 months
description: Postoperative complications (medical, nerve injury, dislocation, hematoma, and wound complications)
measure: Intraoperative complications
time frame: Intraoperative
description: Intraoperative complications (fracture, vascular injury, and anesthesia-related),
measure: Length of surgical procedure
time frame: Intraoperative
description: Length of surgical procedure
arm group label: Local infiltration analgesia group
arm group type: Experimental
description: This group of patients will receive local infiltration analgesia
arm group label: Interscalene block group
arm group type: Active Comparator
description: This group of patients will receive interscalene block
intervention type: Procedure
intervention name: Local infiltration analgesia
description: Local infiltration injection intraoperatively prior to closing during the procedure. A standardized dose of 100 mL of infiltration will be utilized according to the following formula. The mixture will be injected into the deltoid and pectoralis major muscles and fasciae, and subcutaneous tissues using an 18-guage needle.
Total dose 100mL
Ropivacaine 0.5% 40mL Epinephrine 1mg/mL 0.1mL Ketorolac 30mg/mL 1mL Morphine 10mg/mL 0.5mL Normal saline 0.9% 58.4mL
arm group label: Local infiltration analgesia group
intervention type: Procedure
intervention name: Interscalene block
description: Standard interscalene brachial plexus regional block
arm group label: Interscalene block group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
citation: Menendez ME, Lawler SM, Ring D, Jawa A. High pain intensity after total shoulder arthroplasty. J Shoulder Elbow Surg. 2018 Dec;27(12):2113-2119. doi: 10.1016/j.jse.2018.08.001. Epub 2018 Oct 12.
PMID: 30322752
citation: Bjornholdt KT, Jensen JM, Bendtsen TF, Soballe K, Nikolajsen L. Local infiltration analgesia versus continuous interscalene brachial plexus block for shoulder replacement pain: a randomized clinical trial. Eur J Orthop Surg Traumatol. 2015 Dec;25(8):1245-52. doi: 10.1007/s00590-015-1678-2. Epub 2015 Aug 15.
PMID: 26276164
citation: Namdari S, Nicholson T, Abboud J, Lazarus M, Steinberg D, Williams G. Interscalene Block with and without Intraoperative Local Infiltration with Liposomal Bupivacaine in Shoulder Arthroplasty: A Randomized Controlled Trial. J Bone Joint Surg Am. 2018 Aug 15;100(16):1373-1378. doi: 10.2106/JBJS.17.01416.
PMID: 30106818
citation: Namdari S, Nicholson T, Abboud J, Lazarus M, Steinberg D, Williams G. Randomized Controlled Trial of Interscalene Block Compared with Injectable Liposomal Bupivacaine in Shoulder Arthroplasty. J Bone Joint Surg Am. 2017 Apr 5;99(7):550-556. doi: 10.2106/JBJS.16.00296.
PMID: 28375887
citation: Okoroha KR, Lynch JR, Keller RA, Korona J, Amato C, Rill B, Kolowich PA, Muh SJ. Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty: a prospective randomized trial. J Shoulder Elbow Surg. 2016 Nov;25(11):1742-1748. doi: 10.1016/j.jse.2016.05.007. Epub 2016 Jul 14.
PMID: 27422692
citation: Sabesan VJ, Shahriar R, Petersen-Fitts GR, Whaley JD, Bou-Akl T, Sweet M, Milia M. A prospective randomized controlled trial to identify the optimal postoperative pain management in shoulder arthroplasty: liposomal bupivacaine versus continuous interscalene catheter. J Shoulder Elbow Surg. 2017 Oct;26(10):1810-1817. doi: 10.1016/j.jse.2017.06.044. Epub 2017 Aug 24.
PMID: 28844420
citation: Abdallah FW, Halpern SH, Aoyama K, Brull R. Will the Real Benefits of Single-Shot Interscalene Block Please Stand Up? A Systematic Review and Meta-Analysis. Anesth Analg. 2015 May;120(5):1114-1129. doi: 10.1213/ANE.0000000000000688.
PMID: 25822923
citation: Sicard J, Klouche S, Conso C, Billot N, Auregan JC, Poulain S, Lespagnol F, Solignac N, Bauer T, Ferrand M, Hardy P. Local infiltration analgesia versus interscalene nerve block for postoperative pain control after shoulder arthroplasty: a prospective, randomized, comparative noninferiority study involving 99 patients. J Shoulder Elbow Surg. 2019 Feb;28(2):212-219. doi: 10.1016/j.jse.2018.09.026. Epub 2018 Dec 10.
PMID: 30545786
citation: Weller WJ, Azzam MG, Smith RA, Azar FM, Throckmorton TW. Liposomal Bupivacaine Mixture Has Similar Pain Relief and Significantly Fewer Complications at Less Cost Compared to Indwelling Interscalene Catheter in Total Shoulder Arthroplasty. J Arthroplasty. 2017 Nov;32(11):3557-3562. doi: 10.1016/j.arth.2017.03.017. Epub 2017 Mar 16.
PMID: 28390888
citation: Andersen LO, Kehlet H. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty: a systematic review. Br J Anaesth. 2014 Sep;113(3):360-74. doi: 10.1093/bja/aeu155. Epub 2014 Jun 17.
PMID: 24939863
citation: Tashjian RZ, Hung M, Keener JD, Bowen RC, McAllister J, Chen W, Ebersole G, Granger EK, Chamberlain AM. Determining the minimal clinically important difference for the American Shoulder and Elbow Surgeons score, Simple Shoulder Test, and visual analog scale (VAS) measuring pain after shoulder arthroplasty. J Shoulder Elbow Surg. 2017 Jan;26(1):144-148. doi: 10.1016/j.jse.2016.06.007. Epub 2016 Aug 18.
PMID: 27545048
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: H. Mike Kim
investigator title: ASSOCIATE PROFESSOR OF CLINICAL ORTHOPAEDIC SURGERY
mesh term: Osteoarthritis
mesh term: Joint Diseases
mesh term: Rotator Cuff Tear Arthropathy
mesh term: Rotator Cuff Injuries
sharing ipd: Yes
ipd description: Individual participant data (IPD) will be shared with other members of the research team.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Data will be shared from actual study date until actual completion date
ipd access criteria: Treating relationship with a research team member listed on the IRB application.
Research team members will work directly with providers that have a treating (patient-provider) relationship