<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/NCT04471402</url>
  </required_header>
  <id_info>
    <org_study_id>Precedex PG study</org_study_id>
    <nct_id>NCT04471402</nct_id>
  </id_info>
  <brief_title>Determining the Pharmacogenetic Basis of Non-responsiveness to the Sedative Effects of Dexmedetomidine in Children</brief_title>
  <official_title>Determining the Pharmacogenetic Basis of Non-responsiveness to the Sedative Effects of Dexmedetomidine in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hong Kong Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hong Kong Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intranasal Dexmedetomidine is one of the sedative drugs of choice commonly used as an&#xD;
      anxiolytic premedication for children for diagnostic or therapeutic procedures. However, some&#xD;
      children do not achieve the level of sedation expected with the usual dose after an expected&#xD;
      timeframe, leading to distress and costly time wasted.&#xD;
&#xD;
      In this study, we would try to identify a genetic basis to non-responders of Dexmedetomidine&#xD;
      by comparing a chosen gene panel of 250 relevant genes between responders and non-responders&#xD;
      to a standardized 3mcg/kg intranasal Dexmedetomidine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For most children, having to endure a diagnostic or therapeutic procedure in a hospital&#xD;
      environment is a frightening and distressing experience, especially if it is accompanied by&#xD;
      pain or discomfort. In an attempt to minimise the trauma and to maximise co-operation from&#xD;
      the child, administration of a sedative is often requested by either the parent or the&#xD;
      proceduralist. Some sedative agents may have the side effect reducing the child's efforts in&#xD;
      breathing, causing inadequate oxygen to be delivered to and carbon dioxide removed from the&#xD;
      body, a state that can be life threatening if left untreated. Other sedative agents may cause&#xD;
      unpleasant sensations such as hallucinations or nausea while still others may have a&#xD;
      paradoxical effect of exciting rather than sedating the child. Among the available agents&#xD;
      that may be administered without the presence of an attendant anaesthesiologist,&#xD;
      dexmedetomidine is an agent of choice with minimal incidence of the aforementioned effects.&#xD;
      However, we have observed in a small proportion of children that dexmedetomidine does not see&#xD;
      to be able to elicit a sedative response in the expected time and with the usual dose. It is&#xD;
      possible that there is a genetic bas to this resistance and it would be of great use to be&#xD;
      able to predict the non-responders ahead of time so an appropriate alternative may be&#xD;
      selected without a trial and error approach.&#xD;
&#xD;
      In this project, children who would require Precedex as first-line sedation for radiological&#xD;
      or pre-anaesthesia sedation are asked to participate by providing a buccal swab sample and&#xD;
      have their genome (genetic makeup) characterised by target sequencing. They are standardized&#xD;
      into receiving 3mcg/kg intranasal Precedex and are observed every 5 minutes afterwards for&#xD;
      their level of sedation. They would be identified as 'fast responder', 'normal responder',&#xD;
      'slow responder' and 'definite non-responder'.&#xD;
&#xD;
      A gene panel of 250 relevant genes is chosen and compared between the different groups of&#xD;
      responders and non-responders. We will then try to look for the differences between these&#xD;
      groups and we will use this information to build a predictive model. This model will help to&#xD;
      identify non-responders in the future and this would allow clinicians to prepare for an&#xD;
      alternative approach to sedation. This would save time, distress to the child and parent and&#xD;
      ultimately cost to the institution.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Sedative response to intranasal Precedex</measure>
    <time_frame>Every 5 minutes till 30 minutes from administration of intranasal Precedex</time_frame>
    <description>Sedation response is recorded every 5 minutes after administration of Precedex until a satisfactory sedation level is reached. A satisfactory sedation level is defined as a UMSS of 3-4 (University of Michigan Sedation Scale) and allowing transfer to bed without waking up. Subjects are categorized into 'fast responder', 'normal responder', 'slow responder' and 'definite non-responder' based on the time required to achieve satisfactory level of sedation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Onset time of sedation</measure>
    <time_frame>45 minutes from administration of intranasal Precedex</time_frame>
    <description>The actual time required to reach a satisfactory sedation level after administration of intranasal Precedex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of bradycardia</measure>
    <time_frame>2 hour from administration of intranasal Precedex or until administration of other sedative or anaesthetic drugs, whichever is shorter</time_frame>
    <description>Defined as more than 20% reduction in heart rate from baseline or from the lower limit of published normal values for age, whichever is lower</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hypotension</measure>
    <time_frame>2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter</time_frame>
    <description>Defined as a systolic blood pressure more than 20% lower than the published normal values for age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hypertension</measure>
    <time_frame>2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter</time_frame>
    <description>Defined as a systolic blood pressure more than 20% higher than the published normal values for age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hypoxia</measure>
    <time_frame>2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter</time_frame>
    <description>Defined as a SpO2 &lt; or equal to 93% or more than 5% decrease from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wake up time</measure>
    <time_frame>1 hour after completion of procedure</time_frame>
    <description>Time to reach UMSS of 1 or below after completion of procedure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of procedure</measure>
    <time_frame>3 hours</time_frame>
    <description>Length of procedure is recorded</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Pharmacogenetic Study</condition>
  <condition>Procedural Anxiety</condition>
  <condition>Dexmedetomidine</condition>
  <arm_group>
    <arm_group_label>All subjects recruited</arm_group_label>
    <description>All subjects recruited will be given 3mcg/kg intranasal Precedex through an atomiser, divided equally between two nostrils. They will be observed and sedation score will be recorded every 5 minutes according to the University of Michigan Sedation Scale (UMSS). Pulse oximetry and Blood pressure cuff will be applied whenever they accept these monitoring.&#xD;
A buccal swab sample will be taken from all children and the identified genes will be analysed and compared between the different responders (fast, normal, slow or non-responders).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Precedex</intervention_name>
    <description>Intranasal Precedex 3mcg/kg</description>
    <arm_group_label>All subjects recruited</arm_group_label>
    <other_name>Dexmedetomidine</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Buccal swab samples are taken from subjects for DNA analysis&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children who require intranasal Precedex at 3 mcg/kg as an anxiolytic premedication for&#xD;
        radiological or pre-anaesthesia sedation in Hong Kong Children's Hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children who would receive 3mcg/kg intranasal Precedex as a first line sedative agent&#xD;
             for radiological procedures or for pre-anaesthesia sedation&#xD;
&#xD;
          -  Written informed consent from parent or legal guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy or hypersensitivity to Precedex&#xD;
&#xD;
          -  Pre-existing developmental delay&#xD;
&#xD;
          -  Neurological impairment&#xD;
&#xD;
          -  Autism&#xD;
&#xD;
          -  Fever (temperature &gt;/= 38.5c)&#xD;
&#xD;
          -  Major organ dysfunction&#xD;
&#xD;
          -  Cardiac arrhythmia&#xD;
&#xD;
          -  Cardiac failure&#xD;
&#xD;
          -  Subjects who would require a dose exceeding 100mcg if 3mcg/kg dose is achieved&#xD;
&#xD;
          -  Subjects who have failed intranasal administration of Dexmedetomidine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vivian MY Yuen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hong Kong Children's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vivian MY Yuen, M.D.</last_name>
    <phone>+852 57413131</phone>
    <email>yuenmyv@ha.org.hk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jacqueline CK Tse, MBBS</last_name>
    <phone>+852 57413200</phone>
    <email>tck030@ha.org.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hong Kong Children's Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vivian MY Yuen, M.D.</last_name>
      <phone>+852 57413131</phone>
      <email>yuenmyv@ha.org.hk</email>
    </contact>
    <contact_backup>
      <last_name>Jacqueline CK Tse, MBBS</last_name>
      <phone>+852 57413200</phone>
      <email>tck030@ha.org.hk</email>
    </contact_backup>
    <investigator>
      <last_name>Siu Wai Choi, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gordon TC Wong, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Procedural anxiety in children</keyword>
  <keyword>Pharmacogenetic study</keyword>
  <keyword>Dexmedetomidine</keyword>
  <keyword>Sedation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04471402
org study id: Precedex PG study
nct id: NCT04471402
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Intranasal Dexmedetomidine is one of the sedative drugs of choice commonly used as an
      anxiolytic premedication for children for diagnostic or therapeutic procedures. However, some
      children do not achieve the level of sedation expected with the usual dose after an expected
      timeframe, leading to distress and costly time wasted.

      In this study, we would try to identify a genetic basis to non-responders of Dexmedetomidine
      by comparing a chosen gene panel of 250 relevant genes between responders and non-responders
      to a standardized 3mcg/kg intranasal Dexmedetomidine.
For most children, having to endure a diagnostic or therapeutic procedure in a hospital
      environment is a frightening and distressing experience, especially if it is accompanied by
      pain or discomfort. In an attempt to minimise the trauma and to maximise co-operation from
      the child, administration of a sedative is often requested by either the parent or the
      proceduralist. Some sedative agents may have the side effect reducing the child's efforts in
      breathing, causing inadequate oxygen to be delivered to and carbon dioxide removed from the
      body, a state that can be life threatening if left untreated. Other sedative agents may cause
      unpleasant sensations such as hallucinations or nausea while still others may have a
      paradoxical effect of exciting rather than sedating the child. Among the available agents
      that may be administered without the presence of an attendant anaesthesiologist,
      dexmedetomidine is an agent of choice with minimal incidence of the aforementioned effects.
      However, we have observed in a small proportion of children that dexmedetomidine does not see
      to be able to elicit a sedative response in the expected time and with the usual dose. It is
      possible that there is a genetic bas to this resistance and it would be of great use to be
      able to predict the non-responders ahead of time so an appropriate alternative may be
      selected without a trial and error approach.

      In this project, children who would require Precedex as first-line sedation for radiological
      or pre-anaesthesia sedation are asked to participate by providing a buccal swab sample and
      have their genome (genetic makeup) characterised by target sequencing. They are standardized
      into receiving 3mcg/kg intranasal Precedex and are observed every 5 minutes afterwards for
      their level of sedation. They would be identified as 'fast responder', 'normal responder',
      'slow responder' and 'definite non-responder'.

      A gene panel of 250 relevant genes is chosen and compared between the different groups of
      responders and non-responders. We will then try to look for the differences between these
      groups and we will use this information to build a predictive model. This model will help to
      identify non-responders in the future and this would allow clinicians to prepare for an
      alternative approach to sedation. This would save time, distress to the child and parent and
      ultimately cost to the institution.
observational model: Cohort
time perspective: Prospective
measure: Sedative response to intranasal Precedex
time frame: Every 5 minutes till 30 minutes from administration of intranasal Precedex
description: Sedation response is recorded every 5 minutes after administration of Precedex until a satisfactory sedation level is reached. A satisfactory sedation level is defined as a UMSS of 3-4 (University of Michigan Sedation Scale) and allowing transfer to bed without waking up. Subjects are categorized into 'fast responder', 'normal responder', 'slow responder' and 'definite non-responder' based on the time required to achieve satisfactory level of sedation
measure: Onset time of sedation
time frame: 45 minutes from administration of intranasal Precedex
description: The actual time required to reach a satisfactory sedation level after administration of intranasal Precedex
measure: Incidence of bradycardia
time frame: 2 hour from administration of intranasal Precedex or until administration of other sedative or anaesthetic drugs, whichever is shorter
description: Defined as more than 20% reduction in heart rate from baseline or from the lower limit of published normal values for age, whichever is lower
measure: Incidence of hypotension
time frame: 2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter
description: Defined as a systolic blood pressure more than 20% lower than the published normal values for age
measure: Incidence of hypertension
time frame: 2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter
description: Defined as a systolic blood pressure more than 20% higher than the published normal values for age
measure: Incidence of hypoxia
time frame: 2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter
description: Defined as a SpO2 < or equal to 93% or more than 5% decrease from baseline
measure: Wake up time
time frame: 1 hour after completion of procedure
description: Time to reach UMSS of 1 or below after completion of procedure
measure: Length of procedure
time frame: 3 hours
description: Length of procedure is recorded
arm group label: All subjects recruited
description: All subjects recruited will be given 3mcg/kg intranasal Precedex through an atomiser, divided equally between two nostrils. They will be observed and sedation score will be recorded every 5 minutes according to the University of Michigan Sedation Scale (UMSS). Pulse oximetry and Blood pressure cuff will be applied whenever they accept these monitoring.
A buccal swab sample will be taken from all children and the identified genes will be analysed and compared between the different responders (fast, normal, slow or non-responders).
intervention type: Drug
intervention name: Precedex
description: Intranasal Precedex 3mcg/kg
arm group label: All subjects recruited
other name: Dexmedetomidine
Buccal swab samples are taken from subjects for DNA analysis
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 6 Months
maximum age: 12 Years
healthy volunteers: No
last name: Vivian MY Yuen, M.D.
role: Principal Investigator
affiliation: Hong Kong Children's Hospital
last name: Vivian MY Yuen, M.D.
phone: +852 57413131
email: yuenmyv@ha.org.hk
last name: Jacqueline CK Tse, MBBS
phone: +852 57413200
email: tck030@ha.org.hk
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Hong Kong
responsible party type: Sponsor
mesh term: Dexmedetomidine
sharing ipd: No