xml: <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/NCT05975255</url>
    </required_header>
    <id_info>
      <org_study_id>2306-198-1445</org_study_id>
      <nct_id>NCT05975255</nct_id>
    </id_info>
    <brief_title>Dose Finding Study for Remimazolam in Children</brief_title>
    <official_title>Effective Dose of Remimazolam for Loss of Consciousness in Children: A Prospective Dose Finding Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Seoul National University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Seoul National University Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</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>
        This study aims to find effective dose of remimazolam for inducing loss of consciousness in&#xD;
        children aged 2 to 8 years old. We will explore ED90 of remimazolam for loss of consciousness&#xD;
        in 2 minutes after intravenous injection, via a up-and-down method with biased-coin design.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        We will administer remimazolam intravenously to the study participants. Remimazolam will be&#xD;
        infused in 30 seconds to the participants, and we will wait for 2 minutes for the&#xD;
        participants be sedated.&#xD;
  &#xD;
        When a participant was not sedated in 2 minutes, dose of remimazolam in the next participant&#xD;
        will be escalated by 0.05mg/kg. When a participant was sedated in 2 minutes, dose of&#xD;
        remimazolam in the next participant will be decreased by 0.05mg/kg or maintained as same. The&#xD;
        probability of decrement and maintenance will be 90% and 10% respectively. The dose of&#xD;
        remimazolam in the first participant of the study will be 0.05mg/kg.&#xD;
  &#xD;
        We will collect the results and obtain ED90 of remimazolam for loss of consciousness in&#xD;
        children aged 2 to 8 years old.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 31, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>Sequential allocation to drug dosage according to result of previous participant</intervention_model_description>
      <primary_purpose>Supportive Care</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Loss of consciousness</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Score 3 or more in the University of Michigan Sedation Scale in less than 2 minutes after administration of remimazolam besylate</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>UMSS (University of Michigan Sedation Scale)</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Serial measurement of University of Michigan Sedation Scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart rate</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Serial measurement of heart rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pulse oximetry</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Serial measurement of pulse oximetry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Noninvasive mean blood pressure</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Serial measurement of noninvasive mean blood pressure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anesthetic depth</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Serial measurement of electroencephalogram-based anesthetic depth monitoring</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apnea</measure>
      <time_frame>From start of remimazolam administration to 2 minute after end of administration</time_frame>
      <description>Incidence of apnea after administration of remimazolam besylate</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Drug Effect</condition>
    <arm_group>
      <arm_group_label>Study group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Remimazolam administration and evaluation of sedative effect</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Remimazolam besylate</intervention_name>
      <description>Intravenous administration of predetermined dose of Byfavo for 30 seconds</description>
      <arm_group_label>Study group</arm_group_label>
      <other_name>Byfavo</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Children scheduled to undergo general anesthesia or sedation&#xD;
  &#xD;
            -  American Society of Anesthesiologist Physical Status of 1 or 2&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence of Upper respiratory tract infection or any pulmonary disease&#xD;
  &#xD;
            -  Presence of subglottic stenosis, laryngomalacia, or tracheomalacia&#xD;
  &#xD;
            -  History of hypersensitivity to benzodiazepines or propofol&#xD;
  &#xD;
            -  History of hypersensitivity to beans or peanut&#xD;
  &#xD;
            -  History of seizure&#xD;
  &#xD;
            -  Presence of arrhythmia, tachycardia, or bradycardia&#xD;
  &#xD;
            -  Presence of acute closed-angle glaucoma&#xD;
  &#xD;
            -  Patients with unstable vital sign&#xD;
  &#xD;
            -  Presence of sleep apnea&#xD;
  &#xD;
            -  Presence of galactose intolerance, Lapp lactase deficiency, or glucose-galactose&#xD;
               absorption disorder&#xD;
  &#xD;
            -  History of hypersensitivity to dextran 40&#xD;
  &#xD;
            -  Refusal to enroll by one or more parents or legal guardian&#xD;
  &#xD;
            -  Other conditions the researchers regarded as inappropriate to enroll&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>2 Years</minimum_age>
      <maximum_age>8 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jin-Tae Kim, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Seoul National University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Sang-Hwan Ji, M.D., Ph.D.</last_name>
      <phone>82-2-2072-3661</phone>
      <email>jsh1@snu.ac.kr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Seoul National University Hospital</name>
        <address>
          <city>Seoul</city>
          <zip>03080</zip>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
    <reference>
      <citation>Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, Wiard RP, Feldman PL, Collins H, Waszczak BL, Tilbrook GS. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology. 2007 Jul;107(1):60-6. doi: 10.1097/01.anes.0000267503.85085.c0.</citation>
      <PMID>17585216</PMID>
    </reference>
    <reference>
      <citation>Gorges M, Zhou G, Brant R, Ansermino JM. Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications. Paediatr Anaesth. 2017 Mar;27(3):240-247. doi: 10.1111/pan.13088. Epub 2017 Feb 17.</citation>
      <PMID>28211193</PMID>
    </reference>
    <reference>
      <citation>Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20.</citation>
      <PMID>22190555</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
      <investigator_full_name>Jin-Tae Kim</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Remimazolam</keyword>
    <keyword>Children</keyword>
    <keyword>Dose</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05975255
  org study id: 2306-198-1445
  nct id: NCT05975255
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: Yes
  This study aims to find effective dose of remimazolam for inducing loss of consciousness in
        children aged 2 to 8 years old. We will explore ED90 of remimazolam for loss of consciousness
        in 2 minutes after intravenous injection, via a up-and-down method with biased-coin design.
  We will administer remimazolam intravenously to the study participants. Remimazolam will be
        infused in 30 seconds to the participants, and we will wait for 2 minutes for the
        participants be sedated.
  
        When a participant was not sedated in 2 minutes, dose of remimazolam in the next participant
        will be escalated by 0.05mg/kg. When a participant was sedated in 2 minutes, dose of
        remimazolam in the next participant will be decreased by 0.05mg/kg or maintained as same. The
        probability of decrement and maintenance will be 90% and 10% respectively. The dose of
        remimazolam in the first participant of the study will be 0.05mg/kg.
  
        We will collect the results and obtain ED90 of remimazolam for loss of consciousness in
        children aged 2 to 8 years old.
  allocation: N/A
  intervention model: Sequential Assignment
  intervention model description: Sequential allocation to drug dosage according to result of previous participant
  primary purpose: Supportive Care
  masking: None (Open Label)
  measure: Loss of consciousness
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Score 3 or more in the University of Michigan Sedation Scale in less than 2 minutes after administration of remimazolam besylate
  measure: UMSS (University of Michigan Sedation Scale)
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Serial measurement of University of Michigan Sedation Scale
  measure: Heart rate
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Serial measurement of heart rate
  measure: Pulse oximetry
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Serial measurement of pulse oximetry
  measure: Noninvasive mean blood pressure
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Serial measurement of noninvasive mean blood pressure
  measure: Anesthetic depth
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Serial measurement of electroencephalogram-based anesthetic depth monitoring
  measure: Apnea
  time frame: From start of remimazolam administration to 2 minute after end of administration
  description: Incidence of apnea after administration of remimazolam besylate
  arm group label: Study group
  arm group type: Experimental
  description: Remimazolam administration and evaluation of sedative effect
  intervention type: Drug
  intervention name: Remimazolam besylate
  description: Intravenous administration of predetermined dose of Byfavo for 30 seconds
  arm group label: Study group
  other name: Byfavo
  criteria: 
  gender: All
  minimum age: 2 Years
  maximum age: 8 Years
  healthy volunteers: No
  last name: Jin-Tae Kim, M.D., Ph.D.
  role: Principal Investigator
  affiliation: Seoul National University Hospital
  last name: Sang-Hwan Ji, M.D., Ph.D.
  phone: 82-2-2072-3661
  email: jsh1@snu.ac.kr
  facility: 
  country: Korea, Republic of
  citation: Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, Wiard RP, Feldman PL, Collins H, Waszczak BL, Tilbrook GS. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology. 2007 Jul;107(1):60-6. doi: 10.1097/01.anes.0000267503.85085.c0.
  PMID: 17585216
  citation: Gorges M, Zhou G, Brant R, Ansermino JM. Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications. Paediatr Anaesth. 2017 Mar;27(3):240-247. doi: 10.1111/pan.13088. Epub 2017 Feb 17.
  PMID: 28211193
  citation: Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20.
  PMID: 22190555
  responsible party type: Principal Investigator
  investigator affiliation: Seoul National University Hospital
  investigator full name: Jin-Tae Kim
  investigator title: Professor
  sharing ipd: No