<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/NCT01680471</url>
  </required_header>
  <id_info>
    <org_study_id>ECho2012</org_study_id>
    <nct_id>NCT01680471</nct_id>
  </id_info>
  <brief_title>A Study on the Effects of Midazolam on Delirium After Sevoflurane Anesthesia in Pediatric Strabismus Surgery</brief_title>
  <official_title>Comparative Study on the Effects of Capacities of Midazolam on Delirium After Sevoflurane Anesthesia in Pediatric Strabismus Surgery : a Randomized Double- Blinded Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korea University Anam Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Korea University Anam Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sevoflurane with its rapid induction and emergence, hemodynamic stability, and nonirritating&#xD;
      airway properties, has acquired widespread acceptance in children. However, sevoflurane has&#xD;
      been reported to be associated with emergence agitation in children, with a reported&#xD;
      incidence of up to 80%.&#xD;
&#xD;
      The purpose of this study is to verify that the prophylactic use of midazolam, which is a&#xD;
      GABA A receptor inhibitor, given five minutes before the end of strabismus surgery reduces&#xD;
      the incidence of emergence agitation after sevoflurane anesthesia in children.&#xD;
      Simultaneously, this study aims to find out the proper dose of midazolam with minimum&#xD;
      disturbance to patient's emergence time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sevoflurane is associated with a high incidence of emergence agitation in children. The&#xD;
      etiology of emergence agitation is unclear. Some studies proposed that emergence agitation&#xD;
      was related to a variable rate of neurologic recovery rate in different brain areas and&#xD;
      immaturity of neurons. Inhalation anesthetics have been known to exert transient paradoxical&#xD;
      excitatory effects in both animals and human patients, especially in children. The&#xD;
      gamma(γ)-aminobutyric acid (GABA)A receptor is the target depressant effect site of most&#xD;
      anesthetic drugs including sevoflurane. Midazolam acts on the benzodiazepine binding site of&#xD;
      GABAA receptors and results in inhibitory effects on the central nervous system. The effect&#xD;
      of midazolam premedication, as well as midazolam administration at the end of surgery, on&#xD;
      suppressing emergence agitation has been studied. However, the effect of midazolam on&#xD;
      emergence agitation is still controversial. This study aims to figure out the effect of&#xD;
      midazolam at the end of surgery on emergence agitation during the recovery period, and find&#xD;
      out the proper dose of midazolam with minimum disturbance to patient's emergence time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">November 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time of emergence</measure>
    <time_frame>within the first 1hour after end of surgery</time_frame>
    <description>The time of emergence is defined as time interval from the time of discontinuation of sevoflurane to the time of extubation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of emergency agitation</measure>
    <time_frame>From just after extubation until the discharge of PACU, assessed up to 1 hour</time_frame>
    <description>Agitation is assessed immediately after extubation, and continuously thereafter until participants are calm. Emergence agitation is evaluated using the four-point emergence scale and the pediatric anesthesia emergence delirium scale. The highest scores are recorded.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Child</condition>
  <condition>Anesthesia Morbidity</condition>
  <condition>Delirium on Emergence</condition>
  <arm_group>
    <arm_group_label>Midazolam 0.03mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group will be injected intravenous midazolam 0.03mg/kg five minutes before the end of surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam 0.05mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group will be injected intravenous midazolam 0.05mg/kg five minutes before the end of surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>This group will be injected intravenous normal saline five minutes before the end of surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam 0.03mg/kg</intervention_name>
    <description>This group will be injected intravenous midazolam 0.03mg/kg five minutes before the end of surgery.&#xD;
If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.</description>
    <arm_group_label>Midazolam 0.03mg/kg</arm_group_label>
    <other_name>MIDAZOLAM BUKWANG INJ 5mg/5ml</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam 0.05mg/kg</intervention_name>
    <description>This group will be injected intravenous midazolam 0.05mg/kg five minutes before the end of surgery.&#xD;
If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.</description>
    <arm_group_label>Midazolam 0.05mg/kg</arm_group_label>
    <other_name>MIDAZOLAM BUKWANG INJ 5mg/5ml</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>This group will be injected intravenous normal saline five minutes before the end of surgery.&#xD;
If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>NORMAL SALINE INJ(Sodium chloride 9g/1000mL)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists physical status I and II patients&#xD;
&#xD;
          -  Aged one to 13 years scheduled to undergo strabismus surgery under general anesthesia&#xD;
&#xD;
          -  Willing to be assigned to any of the study intervention groups&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal by parents&#xD;
&#xD;
          -  Neurological disease&#xD;
&#xD;
          -  Developmental delay&#xD;
&#xD;
          -  History of any previous surgery&#xD;
&#xD;
          -  Airway disease&#xD;
&#xD;
          -  American Society of Anesthesiologists physical status score of III or IV&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>13 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eun Jung Cho, Resident</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anaesthesiology and Pain Medicine Department, Korea University Anam Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>S.Z. Yoon, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Department of Anaesthesiology and Pain Medicine Department, Korea University Anam Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Anaesthesiology and Pain Medicine Department; Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>136-705</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>January 2013</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>January 3, 2013</last_update_submitted>
  <last_update_submitted_qc>January 3, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 4, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Korea University Anam Hospital</investigator_affiliation>
    <investigator_full_name>Eun Jung Cho</investigator_full_name>
    <investigator_title>Anesthesiology and Pain Medicine Department</investigator_title>
  </responsible_party>
  <keyword>emergence agitation</keyword>
  <keyword>midazolam</keyword>
  <keyword>sevoflurane</keyword>
  <keyword>strabismus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Strabismus</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>Midazolam</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01680471
org study id: ECho2012
nct id: NCT01680471
lead sponsor: 
has dmc: Yes
Sevoflurane with its rapid induction and emergence, hemodynamic stability, and nonirritating
      airway properties, has acquired widespread acceptance in children. However, sevoflurane has
      been reported to be associated with emergence agitation in children, with a reported
      incidence of up to 80%.

      The purpose of this study is to verify that the prophylactic use of midazolam, which is a
      GABA A receptor inhibitor, given five minutes before the end of strabismus surgery reduces
      the incidence of emergence agitation after sevoflurane anesthesia in children.
      Simultaneously, this study aims to find out the proper dose of midazolam with minimum
      disturbance to patient's emergence time.
Sevoflurane is associated with a high incidence of emergence agitation in children. The
      etiology of emergence agitation is unclear. Some studies proposed that emergence agitation
      was related to a variable rate of neurologic recovery rate in different brain areas and
      immaturity of neurons. Inhalation anesthetics have been known to exert transient paradoxical
      excitatory effects in both animals and human patients, especially in children. The
      gamma(γ)-aminobutyric acid (GABA)A receptor is the target depressant effect site of most
      anesthetic drugs including sevoflurane. Midazolam acts on the benzodiazepine binding site of
      GABAA receptors and results in inhibitory effects on the central nervous system. The effect
      of midazolam premedication, as well as midazolam administration at the end of surgery, on
      suppressing emergence agitation has been studied. However, the effect of midazolam on
      emergence agitation is still controversial. This study aims to figure out the effect of
      midazolam at the end of surgery on emergence agitation during the recovery period, and find
      out the proper dose of midazolam with minimum disturbance to patient's emergence time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time of emergence
time frame: within the first 1hour after end of surgery
description: The time of emergence is defined as time interval from the time of discontinuation of sevoflurane to the time of extubation.
measure: Incidence of emergency agitation
time frame: From just after extubation until the discharge of PACU, assessed up to 1 hour
description: Agitation is assessed immediately after extubation, and continuously thereafter until participants are calm. Emergence agitation is evaluated using the four-point emergence scale and the pediatric anesthesia emergence delirium scale. The highest scores are recorded.
arm group label: Midazolam 0.03mg/kg
arm group type: Experimental
description: This group will be injected intravenous midazolam 0.03mg/kg five minutes before the end of surgery.
arm group label: Midazolam 0.05mg/kg
arm group type: Experimental
description: This group will be injected intravenous midazolam 0.05mg/kg five minutes before the end of surgery.
arm group label: Placebo
arm group type: Placebo Comparator
description: This group will be injected intravenous normal saline five minutes before the end of surgery.
intervention type: Drug
intervention name: Midazolam 0.03mg/kg
description: This group will be injected intravenous midazolam 0.03mg/kg five minutes before the end of surgery.
If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.
arm group label: Midazolam 0.03mg/kg
other name: MIDAZOLAM BUKWANG INJ 5mg/5ml
intervention type: Drug
intervention name: Midazolam 0.05mg/kg
description: This group will be injected intravenous midazolam 0.05mg/kg five minutes before the end of surgery.
If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.
arm group label: Midazolam 0.05mg/kg
other name: MIDAZOLAM BUKWANG INJ 5mg/5ml
intervention type: Drug
intervention name: Placebo
description: This group will be injected intravenous normal saline five minutes before the end of surgery.
If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.
arm group label: Placebo
other name: NORMAL SALINE INJ(Sodium chloride 9g/1000mL)
criteria: 
gender: All
minimum age: 1 Year
maximum age: 13 Years
healthy volunteers: No
last name: Eun Jung Cho, Resident
role: Principal Investigator
affiliation: Department of Anaesthesiology and Pain Medicine Department, Korea University Anam Hospital
last name: S.Z. Yoon, Professor
role: Study Director
affiliation: Department of Anaesthesiology and Pain Medicine Department, Korea University Anam Hospital
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Korea University Anam Hospital
investigator full name: Eun Jung Cho
investigator title: Anesthesiology and Pain Medicine Department
mesh term: Delirium
mesh term: Strabismus
mesh term: Emergence Delirium
mesh term: Midazolam