<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/NCT03229486</url>
  </required_header>
  <id_info>
    <org_study_id>PusanNUYH</org_study_id>
    <nct_id>NCT03229486</nct_id>
  </id_info>
  <brief_title>Effect of Sugammadex vs. Neostigmine/Glycopyrrolate on Pediatric Emergence Delirium in Sevoflurane-rocuronium Anesthesia</brief_title>
  <official_title>A Prospective, Double-blind, Randomized Study to Investigate the Effect of Sugammadex vs. Neostigmine/Glycopyrrolate on Emergence Delirium During Sevoflurane-rocuronium Anesthesia in Pediatric Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pusan National University Yangsan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pusan National University Yangsan Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to investigate the effect of sugammadex vs. a conventional&#xD;
      acetylcholinesterase inhibitor, neostigmine on emergence delirium (ED) during&#xD;
      sevoflurane-rocuronium anesthesia in pediatric patients Additionally, the efficacy features&#xD;
      of sugammadex compared to neostigmine will be examined by measuring the time from start of&#xD;
      administration of reversal agents to recovery of train-of-four (TOF) ratio to 0.7, 0.8, and&#xD;
      0.9.&#xD;
&#xD;
      Although the etiology of ED remains unclear, a sense of suffocation or breathing difficulty&#xD;
      during emergence from anesthesia has been suggested as a possible cause. Thus, reversal of&#xD;
      neuromuscular blockade with sugammadex in pediatric patients maintained with&#xD;
      sevoflurane-rocuronium anesthesia may decrease ED due to its faster reversal of neuromuscular&#xD;
      blockade and decreased possibility of residual blockade.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Emergence delirium (ED) is a postanesthetic phenomenon that develops in the early phase of&#xD;
      general anesthesia recovery, (usually within the first 30 minutes,) and is defined as &quot;a&#xD;
      disturbance in a child's awareness of and attention to his/her environment with&#xD;
      disorientation and perceptual alterations including hypersensitivity to stimuli and&#xD;
      hyperactive motor behavior&quot; . Children are often irritable, uncompromising, uncooperative,&#xD;
      incoherent, and inconsolably crying, moaning, kicking, or thrashing. The incidence of ED&#xD;
      varies from 2 to 80%, occurring more frequently in preschool boys. Risk factors also include&#xD;
      the following: sevoflurane or desflurane anesthesia; ear, nose and throat surgery;&#xD;
      preoperative anxiety. ED is known to increase physical, psychological, and financial burdens&#xD;
      in the postanesthesia care unit, which emphasizes the importance of its prevention.&#xD;
&#xD;
      The aim of this study is to investigate the effect of sugammadex vs. a conventional&#xD;
      acetylcholinesterase inhibitor, neostigmine on emergence delirium (ED) during&#xD;
      sevoflurane-rocuronium anesthesia in pediatric patients Additionally, the efficacy features&#xD;
      of sugammadex compared to neostigmine will be examined by measuring the time from start of&#xD;
      administration of reversal agents to recovery of TOF ratio to 0.7, 0.8, and 0.9.&#xD;
&#xD;
      Although the etiology of ED remains unclear, a sense of suffocation or breathing difficulty&#xD;
      during emergence from anesthesia has been suggested as a possible cause. Thus, reversal of&#xD;
      neuromuscular blockade with sugammadex in pediatric patients maintained with&#xD;
      sevoflurane-rocuronium anesthesia may decrease ED due to its faster reversal of neuromuscular&#xD;
      blockade and decreased possibility of residual blockade.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">December 30, 2019</completion_date>
  <primary_completion_date type="Actual">July 30, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pediatric Anesthesia Emergence Delirium Score</measure>
    <time_frame>within 30 minutes after arrival at post-anesthesia care unit (PACU)</time_frame>
    <description>Maximum Pediatric Anesthesia Emergence Delirium (PAED) score after arrival in the PACU.Higher values represent more emergence delirium (worse) PAED Score is represented with total PAED score summed up of subscales. The total score is reported and it ranges from 0 to 20. Higher score means worse state.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time Recovery of TOF Ratio to 0.7</measure>
    <time_frame>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7, assessed up to 60 minutes</time_frame>
    <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Regular Breathing</measure>
    <time_frame>time from administration of reversal agent to time of deep, regular breathing, assessed up to 60 minutes</time_frame>
    <description>time from administration of reversal agent to time of deep, regular breathing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Awakening</measure>
    <time_frame>time from administration of reversal agent to time of eye opening or child showing purposeful movements, assessed up to 60 minutes</time_frame>
    <description>time from administration of reversal agent to time of eye opening or child showing purposeful movement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Extubation</measure>
    <time_frame>time from administration of reversal agent to time of tracheal extubation, assessed up to 60 minutes</time_frame>
    <description>time from administration of reversal agent to time of tracheal extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time Recovery of TOF Ratio to 0.8</measure>
    <time_frame>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8, assessed up to 60 minutes</time_frame>
    <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time Recovery of TOF Ratio to 0.9</measure>
    <time_frame>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9, assessed up to 60 minutes</time_frame>
    <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Emergence Delirium</condition>
  <arm_group>
    <arm_group_label>Sugammadex Injection [Bridion]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>reversal of neuromuscular blockade with sugammadex</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Neostigmine+Glycopyrronium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugammadex Injection [Bridion]</intervention_name>
    <description>Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
    <arm_group_label>Sugammadex Injection [Bridion]</arm_group_label>
    <other_name>Sugammadex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neostigmine+Glycopyrronium</intervention_name>
    <description>Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
    <arm_group_label>Neostigmine+Glycopyrronium</arm_group_label>
    <other_name>Neostigmine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologist (ASA) physical status I or II, preschool children&#xD;
             scheduled for an elective tonsillectomy with or without adenoidectomy will be included&#xD;
             in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients will be excluded in cases of emergency surgery, developmental, psychological,&#xD;
             cognitive or communication disorders, known or suspected neuromuscular disorders that&#xD;
             may impair neuromuscular blockade, significant renal or hepatic dysfunction,&#xD;
             coagulation disorders, family history of malignant hyperthermia, allergy to any of the&#xD;
             drugs included in the study protocol, or usage of medication known to interact with&#xD;
             rocuronium or sugammadex.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>7 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tae-Kyun Kim, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pusan National University Yangsan Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pusan National University Yangsan Hospital</name>
      <address>
        <city>Yangsan</city>
        <state>Gyeongsangnam-do</state>
        <zip>50612</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Plaud B, Meretoja O, Hofmockel R, Raft J, Stoddart PA, van Kuijk JH, Hermens Y, Mirakhur RK. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009 Feb;110(2):284-94. doi: 10.1097/ALN.0b013e318194caaa.</citation>
    <PMID>19194156</PMID>
  </reference>
  <reference>
    <citation>Locatelli BG, Ingelmo PM, Emre S, Meroni V, Minardi C, Frawley G, Benigni A, Di Marco S, Spotti A, Busi I, Sonzogni V. Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale. Paediatr Anaesth. 2013 Apr;23(4):301-8. doi: 10.1111/pan.12038. Epub 2012 Oct 9.</citation>
    <PMID>23043512</PMID>
  </reference>
  <reference>
    <citation>Pieters BJ, Penn E, Nicklaus P, Bruegger D, Mehta B, Weatherly R. Emergence delirium and postoperative pain in children undergoing adenotonsillectomy: a comparison of propofol vs sevoflurane anesthesia. Paediatr Anaesth. 2010 Oct;20(10):944-50. doi: 10.1111/j.1460-9592.2010.03394.x. Epub 2010 Aug 24.</citation>
    <PMID>20735801</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>June 29, 2017</study_first_submitted>
  <study_first_submitted_qc>July 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <results_first_submitted>February 6, 2020</results_first_submitted>
  <results_first_submitted_qc>March 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 17, 2020</results_first_posted>
  <last_update_submitted>March 3, 2020</last_update_submitted>
  <last_update_submitted_qc>March 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Pusan National University Yangsan Hospital</investigator_affiliation>
    <investigator_full_name>Tae-Kyun Kim</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>emergence delirium</keyword>
  <keyword>tonsillectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Emergence Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycopyrrolate</mesh_term>
    <mesh_term>Neostigmine</mesh_term>
  </intervention_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>July 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03229486/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sugammadex</title>
          <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
        </group>
        <group group_id="P2">
          <title>Neostigmine</title>
          <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>One patient in Neostigmine group was dropped for the violation of protocol.</population>
      <group_list>
        <group group_id="B1">
          <title>Sugammadex</title>
          <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
        </group>
        <group group_id="B2">
          <title>Neostigmine</title>
          <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</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="20"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.9" spread="1"/>
                    <measurement group_id="B2" value="5.5" spread="1.2"/>
                    <measurement group_id="B3" value="5.5" spread="1.1"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </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>South Korea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pediatric Anesthesia Emergence Delirium Score</title>
        <description>Maximum Pediatric Anesthesia Emergence Delirium (PAED) score after arrival in the PACU.Higher values represent more emergence delirium (worse) PAED Score is represented with total PAED score summed up of subscales. The total score is reported and it ranges from 0 to 20. Higher score means worse state.</description>
        <time_frame>within 30 minutes after arrival at post-anesthesia care unit (PACU)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Pediatric Anesthesia Emergence Delirium Score</title>
          <description>Maximum Pediatric Anesthesia Emergence Delirium (PAED) score after arrival in the PACU.Higher values represent more emergence delirium (worse) PAED Score is represented with total PAED score summed up of subscales. The total score is reported and it ranges from 0 to 20. Higher score means worse state.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="12.5" upper_limit="20"/>
                    <measurement group_id="O2" value="18" lower_limit="9.5" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time Recovery of TOF Ratio to 0.7</title>
        <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7</description>
        <time_frame>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7, assessed up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Time Recovery of TOF Ratio to 0.7</title>
          <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.7" spread="37.7"/>
                    <measurement group_id="O2" value="167.4" spread="68.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Regular Breathing</title>
        <description>time from administration of reversal agent to time of deep, regular breathing</description>
        <time_frame>time from administration of reversal agent to time of deep, regular breathing, assessed up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Regular Breathing</title>
          <description>time from administration of reversal agent to time of deep, regular breathing</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="273.8" spread="147.4"/>
                    <measurement group_id="O2" value="345.1" spread="214.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Awakening</title>
        <description>time from administration of reversal agent to time of eye opening or child showing purposeful movement</description>
        <time_frame>time from administration of reversal agent to time of eye opening or child showing purposeful movements, assessed up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Awakening</title>
          <description>time from administration of reversal agent to time of eye opening or child showing purposeful movement</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="275.8" spread="134.6"/>
                    <measurement group_id="O2" value="371.2" spread="195.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Extubation</title>
        <description>time from administration of reversal agent to time of tracheal extubation</description>
        <time_frame>time from administration of reversal agent to time of tracheal extubation, assessed up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Extubation</title>
          <description>time from administration of reversal agent to time of tracheal extubation</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="312.1" spread="155.0"/>
                    <measurement group_id="O2" value="427.3" spread="184.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time Recovery of TOF Ratio to 0.8</title>
        <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8</description>
        <time_frame>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8, assessed up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Time Recovery of TOF Ratio to 0.8</title>
          <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.9" spread="42.7"/>
                    <measurement group_id="O2" value="213.6" spread="81.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time Recovery of TOF Ratio to 0.9</title>
        <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9</description>
        <time_frame>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9, assessed up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugammadex</title>
            <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
          </group>
          <group group_id="O2">
            <title>Neostigmine</title>
            <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</description>
          </group>
        </group_list>
        <measure>
          <title>Time Recovery of TOF Ratio to 0.9</title>
          <description>Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.6" spread="38.2"/>
                    <measurement group_id="O2" value="253.1" spread="128.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Anaphylaxis, bradycardia, vomiting, pain, nausea, hypotension, and headache are monitored at post-anesthetic care unit until the patients discharge. It took 1 hour after administration.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sugammadex</title>
          <description>reversal of neuromuscular blockade with sugammadex&#xD;
Sugammadex Injection [Bridion]: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.</description>
        </group>
        <group group_id="E2">
          <title>Neostigmine</title>
          <description>reversal of neuromuscular blockade with neostigmine &amp; glycopyrrolate&#xD;
Neostigmine+Glycopyrronium: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.</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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </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>Professor</name_or_title>
      <organization>Pusan National University Yangsan Hospital</organization>
      <phone>0553602756</phone>
      <email>anesktk@pusan.ac.kr</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/NCT03229486
org study id: PusanNUYH
nct id: NCT03229486
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The aim of this study is to investigate the effect of sugammadex vs. a conventional
      acetylcholinesterase inhibitor, neostigmine on emergence delirium (ED) during
      sevoflurane-rocuronium anesthesia in pediatric patients Additionally, the efficacy features
      of sugammadex compared to neostigmine will be examined by measuring the time from start of
      administration of reversal agents to recovery of train-of-four (TOF) ratio to 0.7, 0.8, and
      0.9.

      Although the etiology of ED remains unclear, a sense of suffocation or breathing difficulty
      during emergence from anesthesia has been suggested as a possible cause. Thus, reversal of
      neuromuscular blockade with sugammadex in pediatric patients maintained with
      sevoflurane-rocuronium anesthesia may decrease ED due to its faster reversal of neuromuscular
      blockade and decreased possibility of residual blockade.
Emergence delirium (ED) is a postanesthetic phenomenon that develops in the early phase of
      general anesthesia recovery, (usually within the first 30 minutes,) and is defined as "a
      disturbance in a child's awareness of and attention to his/her environment with
      disorientation and perceptual alterations including hypersensitivity to stimuli and
      hyperactive motor behavior" . Children are often irritable, uncompromising, uncooperative,
      incoherent, and inconsolably crying, moaning, kicking, or thrashing. The incidence of ED
      varies from 2 to 80%, occurring more frequently in preschool boys. Risk factors also include
      the following: sevoflurane or desflurane anesthesia; ear, nose and throat surgery;
      preoperative anxiety. ED is known to increase physical, psychological, and financial burdens
      in the postanesthesia care unit, which emphasizes the importance of its prevention.

      The aim of this study is to investigate the effect of sugammadex vs. a conventional
      acetylcholinesterase inhibitor, neostigmine on emergence delirium (ED) during
      sevoflurane-rocuronium anesthesia in pediatric patients Additionally, the efficacy features
      of sugammadex compared to neostigmine will be examined by measuring the time from start of
      administration of reversal agents to recovery of TOF ratio to 0.7, 0.8, and 0.9.

      Although the etiology of ED remains unclear, a sense of suffocation or breathing difficulty
      during emergence from anesthesia has been suggested as a possible cause. Thus, reversal of
      neuromuscular blockade with sugammadex in pediatric patients maintained with
      sevoflurane-rocuronium anesthesia may decrease ED due to its faster reversal of neuromuscular
      blockade and decreased possibility of residual blockade.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Pediatric Anesthesia Emergence Delirium Score
time frame: within 30 minutes after arrival at post-anesthesia care unit (PACU)
description: Maximum Pediatric Anesthesia Emergence Delirium (PAED) score after arrival in the PACU.Higher values represent more emergence delirium (worse) PAED Score is represented with total PAED score summed up of subscales. The total score is reported and it ranges from 0 to 20. Higher score means worse state.
measure: Time Recovery of TOF Ratio to 0.7
time frame: Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7, assessed up to 60 minutes
description: Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7
measure: Time to Regular Breathing
time frame: time from administration of reversal agent to time of deep, regular breathing, assessed up to 60 minutes
description: time from administration of reversal agent to time of deep, regular breathing
measure: Time to Awakening
time frame: time from administration of reversal agent to time of eye opening or child showing purposeful movements, assessed up to 60 minutes
description: time from administration of reversal agent to time of eye opening or child showing purposeful movement
measure: Time to Extubation
time frame: time from administration of reversal agent to time of tracheal extubation, assessed up to 60 minutes
description: time from administration of reversal agent to time of tracheal extubation
measure: Time Recovery of TOF Ratio to 0.8
time frame: Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8, assessed up to 60 minutes
description: Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8
measure: Time Recovery of TOF Ratio to 0.9
time frame: Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9, assessed up to 60 minutes
description: Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9
arm group label: Sugammadex Injection [Bridion]
arm group type: Experimental
description: reversal of neuromuscular blockade with sugammadex
arm group label: Neostigmine+Glycopyrronium
arm group type: Active Comparator
description: reversal of neuromuscular blockade with neostigmine & glycopyrrolate
intervention type: Drug
intervention name: Sugammadex Injection [Bridion]
description: Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.
arm group label: Sugammadex Injection [Bridion]
other name: Sugammadex
intervention type: Drug
intervention name: Neostigmine+Glycopyrronium
description: Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.
arm group label: Neostigmine+Glycopyrronium
other name: Neostigmine
criteria: 
gender: All
minimum age: 2 Years
maximum age: 7 Years
healthy volunteers: No
last name: Tae-Kyun Kim, MD, PhD
role: Principal Investigator
affiliation: Pusan National University Yangsan Hospital
facility: 
country: Korea, Republic of
citation: Plaud B, Meretoja O, Hofmockel R, Raft J, Stoddart PA, van Kuijk JH, Hermens Y, Mirakhur RK. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009 Feb;110(2):284-94. doi: 10.1097/ALN.0b013e318194caaa.
PMID: 19194156
citation: Locatelli BG, Ingelmo PM, Emre S, Meroni V, Minardi C, Frawley G, Benigni A, Di Marco S, Spotti A, Busi I, Sonzogni V. Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale. Paediatr Anaesth. 2013 Apr;23(4):301-8. doi: 10.1111/pan.12038. Epub 2012 Oct 9.
PMID: 23043512
citation: Pieters BJ, Penn E, Nicklaus P, Bruegger D, Mehta B, Weatherly R. Emergence delirium and postoperative pain in children undergoing adenotonsillectomy: a comparison of propofol vs sevoflurane anesthesia. Paediatr Anaesth. 2010 Oct;20(10):944-50. doi: 10.1111/j.1460-9592.2010.03394.x. Epub 2010 Aug 24.
PMID: 20735801
responsible party type: Principal Investigator
investigator affiliation: Pusan National University Yangsan Hospital
investigator full name: Tae-Kyun Kim
investigator title: Associate professor
mesh term: Delirium
mesh term: Emergence Delirium
mesh term: Glycopyrrolate
mesh term: Neostigmine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 