<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/NCT04458467</url>
  </required_header>
  <id_info>
    <org_study_id>Auto Intermittent Boluses</org_study_id>
    <nct_id>NCT04458467</nct_id>
  </id_info>
  <brief_title>Perineural Local Anesthetic Administration With a Continuous Infusion Versus Automatic Intermittent Boluses</brief_title>
  <official_title>Perineural Local Anesthetic Administration With a Continuous Infusion Versus Automatic Intermittent Boluses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a randomized comparison of continuous local anesthetic infusion with patient&#xD;
      controlled boluses (PCA) to automated boluses with PCA for continuous popliteal sciatic nerve&#xD;
      blocks. The goal will be to determine the relationship between method of local anesthetic&#xD;
      administration (continuous with PCA initiated at discharge vs. intermittent dosing with PCA&#xD;
      with a 5-hour delay) for continuous peripheral nerve block and the resulting pain control and&#xD;
      duration of analgesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Specific Aim: To determine the relationship between method of local anesthetic administration&#xD;
      (continuous with PCA vs. intermittent dosing with PCA) for continuous peripheral nerve block&#xD;
      and the resulting pain control.&#xD;
&#xD;
      Hypothesis: The investigators hypothesize that, compared with a traditional fixed, continuous&#xD;
      basal infusion initiated prior to discharge, perineural local anesthetic administered with&#xD;
      variable automated boluses at a lower dose and a 5-hour delay following discharge will (1)&#xD;
      provide at least noninferior analgesia during the period that both techniques are&#xD;
      functioning; and, (2) will result in a longer overall duration of administration [dual&#xD;
      primary end points].&#xD;
&#xD;
      Enrollment: Patients 18 years and older undergoing painful foot and/or ankle surgery will be&#xD;
      offered enrollment.&#xD;
&#xD;
      Block placement: The nerve block site will be cleaned with chlorhexidine gluconate and&#xD;
      isopropyl alcohol (ChloraPrep One-Step, Medi-Flex Hospital Products, Inc., Overland Park, KS,&#xD;
      USA), and a clear, sterile, fenestrated drape applied. The ultrasound probe will be readied&#xD;
      for use and placed to visualize the short-axis (cross-section) of the target nerve. A skin&#xD;
      wheal will be raised at the catheter-placement needle's anticipated point of entry. An 8.9&#xD;
      cm, 17-gauge, insulated needle (FlexTip, Arrow International, Reading, PA, USA) will be used&#xD;
      to place all perineural catheters. The catheter-placement 17G needle will be inserted through&#xD;
      the skin wheal, advanced in-plane beneath the US transducer and directed toward the target&#xD;
      nerve. Normal saline (1-2 mL) will be administered via the needle to open the space around&#xD;
      the nerve.&#xD;
&#xD;
      A flexible non-stimulating perineural catheter (FlexTip, Arrow International, Reading, PA,&#xD;
      USA) will be inserted 2-3 cm past the needle tip. After catheter insertion, Ropivacaine 0.5%&#xD;
      (20 mL) will be administered via the catheter under ultrasound visualization. Sensation in&#xD;
      the tibial and peroneal nerve distributions will be checked for anesthetic effect up to 15&#xD;
      minutes following initial local anesthetic bolus. A &quot;successful&quot; regional block will be&#xD;
      defined as sensory- and motor-block onset in all expected nerve distributions within the 15&#xD;
      minutes following the local anesthetic injection.&#xD;
&#xD;
      The initial local anesthetic bolus may provide complete surgical anesthesia for the&#xD;
      procedure. Patients who desire a general anesthetic or experience a partial block that is not&#xD;
      adequate for surgical anesthesia will receive a general anesthetic. Additional boluses of&#xD;
      Ropivacaine 0.5% and epinephrine may be given, if needed, via the perineural catheter.&#xD;
&#xD;
      Randomization: Subjects will be randomized to one of two treatment groups: (1) automated&#xD;
      regular boluses (ARB) with a 5-hour delay or (2) continuous infusion initiated at discharge&#xD;
      in a 1:1 ratio using computer generated lists sealed in opaque envelopes not opened until&#xD;
      after the nerve has been identified and deemed appropriate for catheter placement.&#xD;
&#xD;
      Postoperative Procedures: Following completion of the procedure in the operating room, an&#xD;
      infusion pump (Infutronix, Natick, Massachusetts) with a 500 mL ropivacaine 0.2% reservoir&#xD;
      will be attached to the patient's perineural catheter. For patients in the continuous&#xD;
      infusion group, the pump will provide a 6 mL/h basal infusion and a 4 mL patient-controlled&#xD;
      bolus with a 30-minute lockout (standard at UCSD). For patients in the automated intermittent&#xD;
      bolus group, the pump will provide an automatic 8 mL bolus once every 2 hours and have a 4 mL&#xD;
      patient-controlled bolus with a 30 minute lockout. In addition, for those in the automated&#xD;
      intermittent bolus group, the infusion pump will be set in a &quot;pause&quot; mode that delays&#xD;
      initiation of the automated bolus doses by 5 hours (this can be over-ridden by patients if&#xD;
      they would like to initiate their perineural infusion earlier than 5 hours).&#xD;
&#xD;
      Data Collection: Data will be gathered from the patients' electronic medical record, by&#xD;
      telephone follow-up, and from the infusion pumps memory. Subjects will be contacted via phone&#xD;
      for the six days following surgery to collect information regarding surgical pain (Numeric&#xD;
      Rating Scale of 0 to 10, with &quot;0&quot; being no pain and &quot;10&quot; being the worst pain ever&#xD;
      experienced), analgesic use, number of sleep disturbances due to pain, and satisfaction with&#xD;
      pain control.&#xD;
&#xD;
      Statistics: This study will be powered for two primary end points: (1) the average NRS&#xD;
      queried on postoperative day 1; and (2) the duration of treatment from when the infusion pump&#xD;
      was initially turned on until the local anesthetic reservoir was exhausted. The dual&#xD;
      hypotheses will be tested with a serial testing strategy, such that Hypothesis 2 will not be&#xD;
      formally tested unless the conclusion of Hypothesis 1 is at least &quot;noninferiority&quot;.&#xD;
      Noninferiority will be assessed by comparing the lower limit of the 95% confidence interval&#xD;
      for the difference on the NRS (range: 0 to 10) to a pre-specified noninferiority margin of&#xD;
      1.7 NRS units. This will provide evidence that the analgesia provided by the novel automated&#xD;
      boluses is no worse than 1.7 NRS units compared to Continuous Basal infusion.&#xD;
&#xD;
      Baseline characteristics of the randomized groups will be summarized with means, standard&#xD;
      deviations, and quartiles. Balance between groups will be assessed. Specifically,&#xD;
      standardized differences will be calculated using Cohen's d whereby the difference in means&#xD;
      or proportions is divided by the pooled standard deviation estimates. Any key variables (age,&#xD;
      sex, height, weight, and BMI) with an absolute standardized difference &gt;0.47 (with&#xD;
      1.96×√(2/n)=0.47) will be noted and included in a linear regression model to obtain an&#xD;
      estimate of the treatment group differences adjusted for the imbalanced covariate(s). If&#xD;
      residuals from the linear regression indicate violations of key assumptions (i.e.&#xD;
      homoscedasticity or Guassian distribution), data transformations and/or alternative&#xD;
      generalized linear models will be applied as appropriate.&#xD;
&#xD;
      Secondary outcomes will also be analyzed by Wilcoxon-Mann-Whitney test, or linear models (or&#xD;
      generalized linear models) as appropriate with covariates for any imbalanced covariates. No&#xD;
      multiplicity adjustments will be applied for these analyses.&#xD;
&#xD;
      Sample size estimate: Power is simulated based on the distribution of pain measured with the&#xD;
      Numeric Rating Scale (NRS) observed in previous studies. Specifically, the investigators&#xD;
      simulate NRS scores from a discrete distribution. This results in an expected interquartile&#xD;
      range 1 to 4, and a median of 3 NRS units. 1000 trials were simulated in which the two&#xD;
      groups, n=35 per group, were assumed to follow the same discrete distribution, submitted each&#xD;
      trial to a Wilcoxon-Mann-Whitney test, and derived 95% confidence intervals. Out of the 1000&#xD;
      trials, 792 (79.2%) correctly resulted in a conclusion of non-inferiority; suggesting that&#xD;
      the probability that the trial correctly concludes non-inferiority is about 80% when the&#xD;
      groups follow exactly equivalent distributions.&#xD;
&#xD;
      If the test for Hypothesis 1 concludes noninferiority (scenario A, B, or C in Figure 1), the&#xD;
      investigators will test for a difference in overall duration of administration again using&#xD;
      the Wilcoxon-Mann-Whitney test.&#xD;
&#xD;
      Power is approximated by a two-sample t-test calculation. Assuming a standard deviation of&#xD;
      SD=37 hours (corresponding to an interquartile range of 50 to 100 hours), the investigators&#xD;
      expect that a sample size of n=35 provides 80% power to detect a mean group difference of 25&#xD;
      hours with a two-sided alpha of 5%.&#xD;
&#xD;
      Total enrollment: 70 subjects plus 30 for misplaced catheters or subjects otherwise unable to&#xD;
      be randomized; and subjects who withdraw. This allows for a possible total of 100 subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Actual">March 16, 2021</completion_date>
  <primary_completion_date type="Actual">March 12, 2021</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Average Pain Queried on First Postoperative Day</measure>
    <time_frame>postoperative day 1</time_frame>
    <description>Rated 0-10 on numeric rating scale the average pain from the recovery room until the data collection call. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Infusion</measure>
    <time_frame>6 days postoperatively</time_frame>
    <description>Number of hours from the time the pump is initiated until local anesthetic reservoir exhaustion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Worst Pain</measure>
    <time_frame>Each of 6 days postoperatively</time_frame>
    <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Pain</measure>
    <time_frame>Each of 6 days postoperatively</time_frame>
    <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Least Pain</measure>
    <time_frame>Each of 6 days postoperatively</time_frame>
    <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Current Pain</measure>
    <time_frame>Each of 6 days postoperatively</time_frame>
    <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Opioid Consumption</measure>
    <time_frame>Each of 6 days postoperatively</time_frame>
    <description>Cumulative opioid consumption during the first 6 days postoperatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep Disturbances Due to Pain</measure>
    <time_frame>Each of 6 nights postoperatively</time_frame>
    <description>Number of awakenings due to pain during the first 6 nights postoperatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numbness in Foot and Ankle</measure>
    <time_frame>Each of 6 days postoperatively</time_frame>
    <description>Rate 0 = normal to 10 = insensate</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Pain, Acute</condition>
  <condition>Anesthesia, Local</condition>
  <condition>Trauma Injury</condition>
  <arm_group>
    <arm_group_label>Continuous Infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Automated Boluses</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Continuous Infusion</intervention_name>
    <description>A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
    <arm_group_label>Continuous Infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Automated Intermittent Boluses</intervention_name>
    <description>Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
    <arm_group_label>Automated Boluses</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients undergoing painful foot and/or ankle surgery with a planned popliteal sciatic&#xD;
             perineural catheter for postoperative analgesia&#xD;
&#xD;
          -  age 18 years or older.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current daily opioid use within the previous 4 weeks&#xD;
&#xD;
          -  Clinical neuro-muscular deficit of either the sciatic nerve and its branches and/or&#xD;
             innervating muscles&#xD;
&#xD;
          -  Morbid obesity [weight &gt; 35 kg/m2]; surgery outside of ipsilateral sciatic and&#xD;
             saphenous nerve distributions&#xD;
&#xD;
          -  Pregnancy [as determined by a urine pregnancy test prior to any study interventions]&#xD;
&#xD;
          -  Incarceration.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brian M Ilfeld, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University California San Diego</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSD Medical Center (Hillcrest and Thornton)</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <results_first_submitted>February 27, 2022</results_first_submitted>
  <results_first_submitted_qc>May 16, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 18, 2022</results_first_posted>
  <last_update_submitted>June 10, 2022</last_update_submitted>
  <last_update_submitted_qc>June 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Brian M. Ilfeld, MD, MS</investigator_full_name>
    <investigator_title>Professor in Residence</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 16, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT04458467/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>One patient did not have a successful initial nerve block. Per protocol, the patient was not randomized and did not complete the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Continuous Infusion</title>
          <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
        </group>
        <group group_id="P2">
          <title>Automated Boluses</title>
          <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Continuous Infusion</title>
          <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
        </group>
        <group group_id="B2">
          <title>Automated Boluses</title>
          <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</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="35"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="70"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="35"/>
                    <count group_id="B2" value="35"/>
                    <count group_id="B3" value="70"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52" spread="18"/>
                    <measurement group_id="B2" value="48" spread="17"/>
                    <measurement group_id="B3" value="50" spread="17"/>
                  </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="35"/>
                    <count group_id="B2" value="35"/>
                    <count group_id="B3" value="70"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="29"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Average Pain Queried on First Postoperative Day</title>
        <description>Rated 0-10 on numeric rating scale the average pain from the recovery room until the data collection call. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
        <time_frame>postoperative day 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Average Pain Queried on First Postoperative Day</title>
          <description>Rated 0-10 on numeric rating scale the average pain from the recovery room until the data collection call. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="1.8" upper_limit="4.8"/>
                    <measurement group_id="O2" value="0.0" lower_limit="0" upper_limit="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.033</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Duration of Infusion</title>
        <description>Number of hours from the time the pump is initiated until local anesthetic reservoir exhaustion</description>
        <time_frame>6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Infusion</title>
          <description>Number of hours from the time the pump is initiated until local anesthetic reservoir exhaustion</description>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74" lower_limit="57" upper_limit="80"/>
                    <measurement group_id="O2" value="119" lower_limit="109" upper_limit="125"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Worst Pain</title>
        <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
        <time_frame>Each of 6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Worst Pain</title>
          <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="3.4"/>
                    <measurement group_id="O2" value="3.3" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" spread="2.4"/>
                    <measurement group_id="O2" value="4.6" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="2.7"/>
                    <measurement group_id="O2" value="3.6" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.1" spread="2.6"/>
                    <measurement group_id="O2" value="3.0" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="2.8"/>
                    <measurement group_id="O2" value="3.3" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" spread="3.2"/>
                    <measurement group_id="O2" value="3.7" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Pain</title>
        <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
        <time_frame>Each of 6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Average Pain</title>
          <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="2.4"/>
                    <measurement group_id="O2" value="1.6" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="2.0"/>
                    <measurement group_id="O2" value="2.0" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="2.0"/>
                    <measurement group_id="O2" value="1.6" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="2.0"/>
                    <measurement group_id="O2" value="1.5" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="1.7"/>
                    <measurement group_id="O2" value="1.7" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="2.0"/>
                    <measurement group_id="O2" value="1.8" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Least Pain</title>
        <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
        <time_frame>Each of 6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Least Pain</title>
          <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.8"/>
                    <measurement group_id="O2" value="0.1" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="1.5"/>
                    <measurement group_id="O2" value="0.7" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="1.7"/>
                    <measurement group_id="O2" value="0.4" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="1.8"/>
                    <measurement group_id="O2" value="0.5" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="1.5"/>
                    <measurement group_id="O2" value="0.7" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="1.5"/>
                    <measurement group_id="O2" value="0.8" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Current Pain</title>
        <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</description>
        <time_frame>Each of 6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Current Pain</title>
          <description>Rated 0-10 on numeric rating scale. &quot;0&quot; represents no pain and &quot;10&quot; represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.</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="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="2.8"/>
                    <measurement group_id="O2" value="1.7" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="2.3"/>
                    <measurement group_id="O2" value="1.6" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="2.0"/>
                    <measurement group_id="O2" value="1.2" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" spread="2.2"/>
                    <measurement group_id="O2" value="1.4" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="1.9"/>
                    <measurement group_id="O2" value="1.9" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="2.1"/>
                    <measurement group_id="O2" value="1.9" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Opioid Consumption</title>
        <description>Cumulative opioid consumption during the first 6 days postoperatively</description>
        <time_frame>Each of 6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Opioid Consumption</title>
          <description>Cumulative opioid consumption during the first 6 days postoperatively</description>
          <units>Tablets</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="1.6"/>
                    <measurement group_id="O2" value="0.7" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="1.9"/>
                    <measurement group_id="O2" value="0.9" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" spread="1.7"/>
                    <measurement group_id="O2" value="0.7" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="1.9"/>
                    <measurement group_id="O2" value="0.5" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="1.5"/>
                    <measurement group_id="O2" value="0.5" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="1.7"/>
                    <measurement group_id="O2" value="0.5" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sleep Disturbances Due to Pain</title>
        <description>Number of awakenings due to pain during the first 6 nights postoperatively</description>
        <time_frame>Each of 6 nights postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Sleep Disturbances Due to Pain</title>
          <description>Number of awakenings due to pain during the first 6 nights postoperatively</description>
          <units>Number of sleep disturbances</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="1.2"/>
                    <measurement group_id="O2" value="0.4" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.6"/>
                    <measurement group_id="O2" value="0.5" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="1.5"/>
                    <measurement group_id="O2" value="0.2" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.6"/>
                    <measurement group_id="O2" value="0.2" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="1.8"/>
                    <measurement group_id="O2" value="0.3" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="1.5"/>
                    <measurement group_id="O2" value="0.4" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Numbness in Foot and Ankle</title>
        <description>Rate 0 = normal to 10 = insensate</description>
        <time_frame>Each of 6 days postoperatively</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Infusion</title>
            <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
          </group>
          <group group_id="O2">
            <title>Automated Boluses</title>
            <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</description>
          </group>
        </group_list>
        <measure>
          <title>Numbness in Foot and Ankle</title>
          <description>Rate 0 = normal to 10 = insensate</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="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="2.8"/>
                    <measurement group_id="O2" value="8.9" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="3.4"/>
                    <measurement group_id="O2" value="7.9" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="3.7"/>
                    <measurement group_id="O2" value="7.4" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="1.8"/>
                    <measurement group_id="O2" value="7.2" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="5.4" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                    <measurement group_id="O2" value="1.5" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Continuous Infusion</title>
          <description>Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Continuous Infusion: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.</description>
        </group>
        <group group_id="E2">
          <title>Automated Boluses</title>
          <description>Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).&#xD;
Automated Intermittent Boluses: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).</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="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>John Finneran</name_or_title>
      <organization>UC San Diego</organization>
      <phone>(619) 543-2202</phone>
      <email>jfinneran@health.ucsd.edu</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/NCT04458467
org study id: Auto Intermittent Boluses
nct id: NCT04458467
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This will be a randomized comparison of continuous local anesthetic infusion with patient
      controlled boluses (PCA) to automated boluses with PCA for continuous popliteal sciatic nerve
      blocks. The goal will be to determine the relationship between method of local anesthetic
      administration (continuous with PCA initiated at discharge vs. intermittent dosing with PCA
      with a 5-hour delay) for continuous peripheral nerve block and the resulting pain control and
      duration of analgesia.
Specific Aim: To determine the relationship between method of local anesthetic administration
      (continuous with PCA vs. intermittent dosing with PCA) for continuous peripheral nerve block
      and the resulting pain control.

      Hypothesis: The investigators hypothesize that, compared with a traditional fixed, continuous
      basal infusion initiated prior to discharge, perineural local anesthetic administered with
      variable automated boluses at a lower dose and a 5-hour delay following discharge will (1)
      provide at least noninferior analgesia during the period that both techniques are
      functioning; and, (2) will result in a longer overall duration of administration [dual
      primary end points].

      Enrollment: Patients 18 years and older undergoing painful foot and/or ankle surgery will be
      offered enrollment.

      Block placement: The nerve block site will be cleaned with chlorhexidine gluconate and
      isopropyl alcohol (ChloraPrep One-Step, Medi-Flex Hospital Products, Inc., Overland Park, KS,
      USA), and a clear, sterile, fenestrated drape applied. The ultrasound probe will be readied
      for use and placed to visualize the short-axis (cross-section) of the target nerve. A skin
      wheal will be raised at the catheter-placement needle's anticipated point of entry. An 8.9
      cm, 17-gauge, insulated needle (FlexTip, Arrow International, Reading, PA, USA) will be used
      to place all perineural catheters. The catheter-placement 17G needle will be inserted through
      the skin wheal, advanced in-plane beneath the US transducer and directed toward the target
      nerve. Normal saline (1-2 mL) will be administered via the needle to open the space around
      the nerve.

      A flexible non-stimulating perineural catheter (FlexTip, Arrow International, Reading, PA,
      USA) will be inserted 2-3 cm past the needle tip. After catheter insertion, Ropivacaine 0.5%
      (20 mL) will be administered via the catheter under ultrasound visualization. Sensation in
      the tibial and peroneal nerve distributions will be checked for anesthetic effect up to 15
      minutes following initial local anesthetic bolus. A "successful" regional block will be
      defined as sensory- and motor-block onset in all expected nerve distributions within the 15
      minutes following the local anesthetic injection.

      The initial local anesthetic bolus may provide complete surgical anesthesia for the
      procedure. Patients who desire a general anesthetic or experience a partial block that is not
      adequate for surgical anesthesia will receive a general anesthetic. Additional boluses of
      Ropivacaine 0.5% and epinephrine may be given, if needed, via the perineural catheter.

      Randomization: Subjects will be randomized to one of two treatment groups: (1) automated
      regular boluses (ARB) with a 5-hour delay or (2) continuous infusion initiated at discharge
      in a 1:1 ratio using computer generated lists sealed in opaque envelopes not opened until
      after the nerve has been identified and deemed appropriate for catheter placement.

      Postoperative Procedures: Following completion of the procedure in the operating room, an
      infusion pump (Infutronix, Natick, Massachusetts) with a 500 mL ropivacaine 0.2% reservoir
      will be attached to the patient's perineural catheter. For patients in the continuous
      infusion group, the pump will provide a 6 mL/h basal infusion and a 4 mL patient-controlled
      bolus with a 30-minute lockout (standard at UCSD). For patients in the automated intermittent
      bolus group, the pump will provide an automatic 8 mL bolus once every 2 hours and have a 4 mL
      patient-controlled bolus with a 30 minute lockout. In addition, for those in the automated
      intermittent bolus group, the infusion pump will be set in a "pause" mode that delays
      initiation of the automated bolus doses by 5 hours (this can be over-ridden by patients if
      they would like to initiate their perineural infusion earlier than 5 hours).

      Data Collection: Data will be gathered from the patients' electronic medical record, by
      telephone follow-up, and from the infusion pumps memory. Subjects will be contacted via phone
      for the six days following surgery to collect information regarding surgical pain (Numeric
      Rating Scale of 0 to 10, with "0" being no pain and "10" being the worst pain ever
      experienced), analgesic use, number of sleep disturbances due to pain, and satisfaction with
      pain control.

      Statistics: This study will be powered for two primary end points: (1) the average NRS
      queried on postoperative day 1; and (2) the duration of treatment from when the infusion pump
      was initially turned on until the local anesthetic reservoir was exhausted. The dual
      hypotheses will be tested with a serial testing strategy, such that Hypothesis 2 will not be
      formally tested unless the conclusion of Hypothesis 1 is at least "noninferiority".
      Noninferiority will be assessed by comparing the lower limit of the 95% confidence interval
      for the difference on the NRS (range: 0 to 10) to a pre-specified noninferiority margin of
      1.7 NRS units. This will provide evidence that the analgesia provided by the novel automated
      boluses is no worse than 1.7 NRS units compared to Continuous Basal infusion.

      Baseline characteristics of the randomized groups will be summarized with means, standard
      deviations, and quartiles. Balance between groups will be assessed. Specifically,
      standardized differences will be calculated using Cohen's d whereby the difference in means
      or proportions is divided by the pooled standard deviation estimates. Any key variables (age,
      sex, height, weight, and BMI) with an absolute standardized difference >0.47 (with
      1.96×√(2/n)=0.47) will be noted and included in a linear regression model to obtain an
      estimate of the treatment group differences adjusted for the imbalanced covariate(s). If
      residuals from the linear regression indicate violations of key assumptions (i.e.
      homoscedasticity or Guassian distribution), data transformations and/or alternative
      generalized linear models will be applied as appropriate.

      Secondary outcomes will also be analyzed by Wilcoxon-Mann-Whitney test, or linear models (or
      generalized linear models) as appropriate with covariates for any imbalanced covariates. No
      multiplicity adjustments will be applied for these analyses.

      Sample size estimate: Power is simulated based on the distribution of pain measured with the
      Numeric Rating Scale (NRS) observed in previous studies. Specifically, the investigators
      simulate NRS scores from a discrete distribution. This results in an expected interquartile
      range 1 to 4, and a median of 3 NRS units. 1000 trials were simulated in which the two
      groups, n=35 per group, were assumed to follow the same discrete distribution, submitted each
      trial to a Wilcoxon-Mann-Whitney test, and derived 95% confidence intervals. Out of the 1000
      trials, 792 (79.2%) correctly resulted in a conclusion of non-inferiority; suggesting that
      the probability that the trial correctly concludes non-inferiority is about 80% when the
      groups follow exactly equivalent distributions.

      If the test for Hypothesis 1 concludes noninferiority (scenario A, B, or C in Figure 1), the
      investigators will test for a difference in overall duration of administration again using
      the Wilcoxon-Mann-Whitney test.

      Power is approximated by a two-sample t-test calculation. Assuming a standard deviation of
      SD=37 hours (corresponding to an interquartile range of 50 to 100 hours), the investigators
      expect that a sample size of n=35 provides 80% power to detect a mean group difference of 25
      hours with a two-sided alpha of 5%.

      Total enrollment: 70 subjects plus 30 for misplaced catheters or subjects otherwise unable to
      be randomized; and subjects who withdraw. This allows for a possible total of 100 subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Average Pain Queried on First Postoperative Day
time frame: postoperative day 1
description: Rated 0-10 on numeric rating scale the average pain from the recovery room until the data collection call. "0" represents no pain and "10" represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.
measure: Duration of Infusion
time frame: 6 days postoperatively
description: Number of hours from the time the pump is initiated until local anesthetic reservoir exhaustion
measure: Worst Pain
time frame: Each of 6 days postoperatively
description: Rated 0-10 on numeric rating scale. "0" represents no pain and "10" represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.
measure: Average Pain
time frame: Each of 6 days postoperatively
description: Rated 0-10 on numeric rating scale. "0" represents no pain and "10" represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.
measure: Least Pain
time frame: Each of 6 days postoperatively
description: Rated 0-10 on numeric rating scale. "0" represents no pain and "10" represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.
measure: Current Pain
time frame: Each of 6 days postoperatively
description: Rated 0-10 on numeric rating scale. "0" represents no pain and "10" represents worst imaginable pain. Thus, a lower pain score corresponds to less pain.
measure: Opioid Consumption
time frame: Each of 6 days postoperatively
description: Cumulative opioid consumption during the first 6 days postoperatively
measure: Sleep Disturbances Due to Pain
time frame: Each of 6 nights postoperatively
description: Number of awakenings due to pain during the first 6 nights postoperatively
measure: Numbness in Foot and Ankle
time frame: Each of 6 days postoperatively
description: Rate 0 = normal to 10 = insensate
arm group label: Continuous Infusion
arm group type: Active Comparator
description: Patients will receive a continuous infusion of Ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout).
arm group label: Automated Boluses
arm group type: Experimental
description: Patients will receive intermittent boluses of Ropivacaine 0.2% (8 mL automated bolus every 120 minutes, 4 mL patient controlled bolus with 30-minute lockout).
intervention type: Device
intervention name: Continuous Infusion
description: A continuous infusion of ropivacaine 0.2% (6 mL/hr, 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room.
arm group label: Continuous Infusion
intervention type: Device
intervention name: Automated Intermittent Boluses
description: Administration of automated intermittent boluses of ropivacaine 0.2% (8 mL every 2 hr with 4 mL patient controlled bolus with 30-minute lockout) will be initiated in the recovery room, but with a 5-hour delay for the first bolus (can be overridden by patients if they would like to initiate their perineural infusion earlier than 5 hours).
arm group label: Automated Boluses
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brian M Ilfeld, MD, MS
role: Principal Investigator
affiliation: University California San Diego
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Brian M. Ilfeld, MD, MS
investigator title: Professor in Residence
mesh term: Acute Pain
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 