<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/NCT02206685</url>
  </required_header>
  <id_info>
    <org_study_id>H32894</org_study_id>
    <nct_id>NCT02206685</nct_id>
  </id_info>
  <brief_title>A Trial Comparing Single Intra-op Dose of Methadone Versus Placebo in Patients Undergoing Spine Surgery</brief_title>
  <official_title>A Randomized Blinded Prospective Trial Comparing Single Intraoperative Dose of Methadone Versus Placebo in Pediatric Patients Undergoing Spine Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Baylor College of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can&#xD;
      affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which&#xD;
      is a measurement used for evaluation of curves in scoliosis on an anterior-posterior&#xD;
      radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40&#xD;
      degrees in the lumbar region) or when the curvature causes significant pain, or respiratory&#xD;
      and cardiovascular restriction. Patient undergoing this surgical correction experience severe&#xD;
      pain in the postoperative period and the management includes the use of opioid-based&#xD;
      patient-controlled analgesia (PCA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can&#xD;
      affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which&#xD;
      is a measurement used for evaluation of curves in scoliosis on an anterior-posterior&#xD;
      radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40&#xD;
      degrees in the lumbar region) or when the curvature causes significant pain, or respiratory&#xD;
      and cardiovascular restriction. Patient undergoing this surgical correction experience severe&#xD;
      pain in the postoperative period and the management includes the use of opioid-based&#xD;
      patient-controlled analgesia (PCA).&#xD;
&#xD;
      Methadone is an opioid with one of the longest elimination half-life and has been used as an&#xD;
      effective analgesic for acute, chronic, neuropathic, and cancer pain in adults, children, and&#xD;
      even neonates1-5. Its long duration of action and antagonism to the N-methyl-d-aspartate&#xD;
      receptor may decrease the need for PCA use in the postoperative period. Gourlay2 demonstrated&#xD;
      the effectiveness and utility of perioperative methadone including the advantages of longer&#xD;
      analgesia with no serious side effects of respiratory depression. A recent study by&#xD;
      Gottschalk2 in adult patients demonstrated a 50% reduction of postoperative opioids at 48&#xD;
      hours and lower pain scores after a single bolus of methadone before surgical incision.&#xD;
      However, a major weakness of the study is that patients did not receive equipotent&#xD;
      intraoperative opioids. In addition, the adolescent patient population will undergo a much&#xD;
      larger surgical incision with potential for greater postoperative pain. Despite this&#xD;
      potential benefit, methadone is seldom used in the perioperative setting. A more recent&#xD;
      pharmacokinetic study of methadone in adolescents undergoing spine surgery failed to show a&#xD;
      reduction in opioid consumption as it was powered to determine pharmacokinetics and not a&#xD;
      secondary endpoint of postoperative opioid consumption. An appropriately powered study is&#xD;
      still required to determine the efficacy of methadone in reducing postoperative pain after&#xD;
      spine surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Actual">January 27, 2020</completion_date>
  <primary_completion_date type="Actual">January 27, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Opioid Usage</measure>
    <time_frame>Admission to PACU to 72 hours post-operative</time_frame>
    <description>Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Scores</measure>
    <time_frame>Admission to PACU to 72 hours post-operative</time_frame>
    <description>The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Thoracolumbar Scoliosis</condition>
  <arm_group>
    <arm_group_label>Treatment group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes</description>
    <arm_group_label>Treatment group</arm_group_label>
    <other_name>Treatment group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>the control group will receive a 20 ml normal saline placebo infusion over 10 minutes</description>
    <arm_group_label>Control Group</arm_group_label>
    <other_name>Control Group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient age 10 - 17 years&#xD;
&#xD;
          2. Patients undergoing multilevel thoraco-lumbar spine surgery with instrumentation and&#xD;
             fusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Preoperative methadone therapy&#xD;
&#xD;
          2. Inability to use the PCA&#xD;
&#xD;
          3. Allergy to methadone or morphine&#xD;
&#xD;
          4. Morbid obesity with a body mass index &gt;36.0 kg/m2&#xD;
&#xD;
          5. Patients with chronic renal failure defined by serum creatinine &gt;2.0 mg/dL&#xD;
&#xD;
          6. Liver failure defined as a history of cirrhosis or fulminant hepatic failure&#xD;
&#xD;
          7. Preoperative congenital heart disease or arrhythmias&#xD;
&#xD;
          8. Patient refusal to participate in study&#xD;
&#xD;
          9. Pregnancy (It is standard of care for all post menarche female patients to undergo a&#xD;
             urine pregnancy test prior to surgery).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kim Nguyen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003971. doi: 10.1002/14651858.CD003971.pub3.</citation>
    <PMID>17943808</PMID>
  </reference>
  <reference>
    <citation>Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.</citation>
    <PMID>6128949</PMID>
  </reference>
  <reference>
    <citation>Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.</citation>
    <PMID>20418538</PMID>
  </reference>
  <reference>
    <citation>Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED. Perioperative pharmacokinetics of methadone in adolescents. Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5.</citation>
    <PMID>22037641</PMID>
  </reference>
  <reference>
    <citation>Berde CB, Beyer JE, Bournaki MC, Levin CR, Sethna NF. Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children. J Pediatr. 1991 Jul;119(1 Pt 1):136-41. doi: 10.1016/s0022-3476(05)81054-6.</citation>
    <PMID>2066846</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <results_first_submitted>December 28, 2020</results_first_submitted>
  <results_first_submitted_qc>January 27, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 16, 2021</results_first_posted>
  <last_update_submitted>January 27, 2021</last_update_submitted>
  <last_update_submitted_qc>January 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
    <investigator_full_name>Kim Nguyen</investigator_full_name>
    <investigator_title>Pediatric Anesthesiologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scoliosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methadone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Methods of statistical analysis may be shared at study completion.</ipd_description>
  </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>January 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT02206685/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment Group</title>
          <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.&#xD;
Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes</description>
        </group>
        <group group_id="P2">
          <title>Control Group</title>
          <description>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes&#xD;
Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Surgery cancelled/changed</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment Group</title>
          <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.&#xD;
Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes</description>
        </group>
        <group group_id="B2">
          <title>Control Group</title>
          <description>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes&#xD;
Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes</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="32"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="62"/>
          </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="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14.09" spread="1.69"/>
                    <measurement group_id="B2" value="14.33" spread="1.69"/>
                    <measurement group_id="B3" value="14.21" spread="1.67"/>
                  </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="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</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="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.26" spread="12.72"/>
                    <measurement group_id="B2" value="53.95" spread="13.20"/>
                    <measurement group_id="B3" value="56.18" spread="12.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</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="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="160.64" spread="9.98"/>
                    <measurement group_id="B2" value="162.48" spread="8.07"/>
                    <measurement group_id="B3" value="161.53" spread="9.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</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="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.45" spread="3.78"/>
                    <measurement group_id="B2" value="20.29" spread="3.89"/>
                    <measurement group_id="B3" value="21.41" spread="3.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA Status</title>
          <description>The ASA (American Society of Anesthesiologists) physical status classification system is a system for assessing the fitness of patients before surgery.&#xD;
ASA I: A normal healthy patient ASA II: A patient with mild systemic disease ASA III: A patient with severe systemic disease</description>
          <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="32"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="62"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>I</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Opioid Usage</title>
        <description>Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively.</description>
        <time_frame>Admission to PACU to 72 hours post-operative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.&#xD;
Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes&#xD;
Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes</description>
          </group>
        </group_list>
        <measure>
          <title>Opioid Usage</title>
          <description>Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively.</description>
          <units>mg/kg</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="32"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PACU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" lower_limit="0.25" upper_limit="0.65"/>
                    <measurement group_id="O2" value="0.47" lower_limit="0.33" upper_limit="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.58" lower_limit="0.34" upper_limit="0.82"/>
                    <measurement group_id="O2" value="0.55" lower_limit="0.37" upper_limit="0.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.58" lower_limit="0.31" upper_limit="0.79"/>
                    <measurement group_id="O2" value="0.55" lower_limit="0.24" upper_limit="0.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" lower_limit="0" upper_limit="0.23"/>
                    <measurement group_id="O2" value="0.04" lower_limit="0" upper_limit="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Scores</title>
        <description>The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively.</description>
        <time_frame>Admission to PACU to 72 hours post-operative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.&#xD;
Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes&#xD;
Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Scores</title>
          <description>The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PACU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.53" spread="0.76"/>
                    <measurement group_id="O2" value="0.65" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.14" spread="0.4"/>
                    <measurement group_id="O2" value="0.42" spread="0.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24" spread="0.45"/>
                    <measurement group_id="O2" value="0.36" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" spread="0.18"/>
                    <measurement group_id="O2" value="0.29" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>At any time during hospitalization (Days 0 to 5)</time_frame>
      <desc>Side effects of Methadone versus Placebo group were assessed during the duration of the subject's hospitalization. Incidents were counted once per subject.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment Group</title>
          <description>The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.&#xD;
Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes</description>
        </group>
        <group group_id="E2">
          <title>Control Group</title>
          <description>The control group will receive a 20 ml normal saline placebo infusion over 10 minutes&#xD;
Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes</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="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea and Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxemia (oxygen required)</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Kim P. Nguyen, MD, Principal Investigator</name_or_title>
      <organization>Baylor College of Medicine</organization>
      <phone>832-824-5907</phone>
      <email>kpnguyen@texaschildrens.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02206685
org study id: H32894
nct id: NCT02206685
lead sponsor: 
has dmc: Yes
Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can
      affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which
      is a measurement used for evaluation of curves in scoliosis on an anterior-posterior
      radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40
      degrees in the lumbar region) or when the curvature causes significant pain, or respiratory
      and cardiovascular restriction. Patient undergoing this surgical correction experience severe
      pain in the postoperative period and the management includes the use of opioid-based
      patient-controlled analgesia (PCA).
Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can
      affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which
      is a measurement used for evaluation of curves in scoliosis on an anterior-posterior
      radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40
      degrees in the lumbar region) or when the curvature causes significant pain, or respiratory
      and cardiovascular restriction. Patient undergoing this surgical correction experience severe
      pain in the postoperative period and the management includes the use of opioid-based
      patient-controlled analgesia (PCA).

      Methadone is an opioid with one of the longest elimination half-life and has been used as an
      effective analgesic for acute, chronic, neuropathic, and cancer pain in adults, children, and
      even neonates1-5. Its long duration of action and antagonism to the N-methyl-d-aspartate
      receptor may decrease the need for PCA use in the postoperative period. Gourlay2 demonstrated
      the effectiveness and utility of perioperative methadone including the advantages of longer
      analgesia with no serious side effects of respiratory depression. A recent study by
      Gottschalk2 in adult patients demonstrated a 50% reduction of postoperative opioids at 48
      hours and lower pain scores after a single bolus of methadone before surgical incision.
      However, a major weakness of the study is that patients did not receive equipotent
      intraoperative opioids. In addition, the adolescent patient population will undergo a much
      larger surgical incision with potential for greater postoperative pain. Despite this
      potential benefit, methadone is seldom used in the perioperative setting. A more recent
      pharmacokinetic study of methadone in adolescents undergoing spine surgery failed to show a
      reduction in opioid consumption as it was powered to determine pharmacokinetics and not a
      secondary endpoint of postoperative opioid consumption. An appropriately powered study is
      still required to determine the efficacy of methadone in reducing postoperative pain after
      spine surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Opioid Usage
time frame: Admission to PACU to 72 hours post-operative
description: Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively.
measure: Pain Scores
time frame: Admission to PACU to 72 hours post-operative
description: The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively.
arm group label: Treatment group
arm group type: Active Comparator
description: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes.
arm group label: Control Group
arm group type: Placebo Comparator
description: The control group will receive a 20 ml normal saline placebo infusion over 10 minutes
intervention type: Drug
intervention name: Methadone
description: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes
arm group label: Treatment group
other name: Treatment group
intervention type: Drug
intervention name: Normal Saline
description: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes
arm group label: Control Group
other name: Control Group
criteria: 
gender: All
minimum age: 10 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kim Nguyen, MD
role: Principal Investigator
affiliation: Baylor College of Medicine
facility: 
country: United States
citation: Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003971. doi: 10.1002/14651858.CD003971.pub3.
PMID: 17943808
citation: Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.
PMID: 6128949
citation: Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
PMID: 20418538
citation: Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED. Perioperative pharmacokinetics of methadone in adolescents. Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5.
PMID: 22037641
citation: Berde CB, Beyer JE, Bournaki MC, Levin CR, Sethna NF. Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children. J Pediatr. 1991 Jul;119(1 Pt 1):136-41. doi: 10.1016/s0022-3476(05)81054-6.
PMID: 2066846
responsible party type: Principal Investigator
investigator affiliation: Baylor College of Medicine
investigator full name: Kim Nguyen
investigator title: Pediatric Anesthesiologist
mesh term: Scoliosis
mesh term: Methadone
sharing ipd: No
ipd description: Methods of statistical analysis may be shared at study completion.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 