<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/NCT03246620</url>
  </required_header>
  <id_info>
    <org_study_id>ChanEW oral sedation RCT</org_study_id>
    <secondary_id>17111615</secondary_id>
    <nct_id>NCT03246620</nct_id>
  </id_info>
  <brief_title>Oral Olanzapine Versus Haloperidol or Diazepam</brief_title>
  <official_title>Oro-dispersible Olanzapine (Wafer) Versus Conventional Oral Haloperidol or Diazepam Tablets for the Management of Acute Agitation in the Accident and Emergency Department - a Multicentre Randomised Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen Elizabeth Hospital, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Hong Kong</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether oral olanzapine is safer (fewer adverse&#xD;
      events) and more effective (shorter time to sedation) than conventional haloperidol or&#xD;
      diazepam when used in the management of acute agitation in the emergency.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Investigate oral use of sedating drugs within a predominantly Chinese population, to&#xD;
           address this void in international literature impacting the management of acute&#xD;
           agitation.&#xD;
&#xD;
        2. The multi-centre Randomised Clinical Trial will determine the safety and efficacy of&#xD;
           oral olanzapine, in comparison with conventional medicines (haloperidol or diazepam) in&#xD;
           a three-arm comparison for the sedation of acutely agitated patients in AEDs.&#xD;
           Specifically, we aim to determine if administration of oral olanzapine (a)is more&#xD;
           effective than sedation with oral haloperidol or oral diazepam alone; (b)is safer than&#xD;
           sedation with comparison arms; (c)decreases the amount of subsequent redosing or&#xD;
           alternative drugs required; (d)is more favourable than the haloperidol and diazepam arms&#xD;
           with respect to safety, efficacy and adverse events.&#xD;
&#xD;
      Investigate potential variables leading to AED attendance and/or admission requiring oral&#xD;
      sedation. These may include patient demographic and regular medications and adherence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was terminated prematurely due to difficulties in patient recruitment and associated&#xD;
    potential for selection bias.&#xD;
  </why_stopped>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">June 1, 2018</completion_date>
  <primary_completion_date type="Actual">June 1, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to achieve adequate sedation</measure>
    <time_frame>Within 60 minutes from drug administration</time_frame>
    <description>Adequate sedation is determined by a 6-point validated scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total study drug doses administered; alternative drugs and doses used</measure>
    <time_frame>From Accident &amp; Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corrected QT interval (QTc)</measure>
    <time_frame>From Accident &amp; Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AED length of stay (LOS)</measure>
    <time_frame>From Accident &amp; Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>From Accident &amp; Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour</time_frame>
    <description>including airway management (jaw thrust, oral, nasal airway), need for assisted ventilation (bag/mask, intubation), oxygen desaturation &lt;90%, systolic BP&lt;90 mmHg, dystonic reactions, seizures, vomiting or aspiration</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Acute Agitation</condition>
  <condition>Behavioural Emergency</condition>
  <arm_group>
    <arm_group_label>Olanzapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oro-dispersible tablet (wafer)(Zyprexa), 5 mg, single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Haloperidol encapsulated tablet, 2 mg tablet, single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diazepam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Diazepam encapsulated tablet, 2mg tablet, single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olanzapine oro-dispersible 5Mg Tab</intervention_name>
    <description>Patient allocated to this arm will be given 5 mg olanzapine oro-dispersible tablet and an encapsulated placebo tablet</description>
    <arm_group_label>Olanzapine</arm_group_label>
    <other_name>Zyprexa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol 2Mg encapsulated Tab</intervention_name>
    <description>Patient allocated to this arm will be given 2 mg encapsulated haloperidol tablet and an oro-dispersible placebo tablet</description>
    <arm_group_label>Haloperidol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diazepam 2Mg encapsulated Tab</intervention_name>
    <description>Patient allocated to this arm will be given 2 mg encapsulated diazepam tablet and an oro-dispersible placebo tablet</description>
    <arm_group_label>Diazepam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Accident &amp; Emergency Department patients&#xD;
&#xD;
          -  Requiring oral drug sedation (as determined by an emergency clinician) will be&#xD;
             enrolled.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known hypersensitivity or contraindication to the study drugs&#xD;
&#xD;
          -  reversible aetiology for agitation (e.g. hypotension, hypoxia, hypoglycaemia)&#xD;
&#xD;
          -  known pregnancy&#xD;
&#xD;
          -  acute alcohol withdrawal&#xD;
&#xD;
          -  refusal to take oral medication&#xD;
&#xD;
          -  patients from correctional facilities&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <reference>
    <citation>Knott JC, Bennett D, Rawet J, Taylor DM. Epidemiology of unarmed threats in the emergency department. Emerg Med Australas. 2005 Aug;17(4):351-8. doi: 10.1111/j.1742-6723.2005.00756.x.</citation>
    <PMID>16091097</PMID>
  </reference>
  <reference>
    <citation>Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013 Jan;61(1):72-81. doi: 10.1016/j.annemergmed.2012.07.118. Epub 2012 Sep 13.</citation>
    <PMID>22981685</PMID>
  </reference>
  <reference>
    <citation>Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med. 2006 Jan;47(1):61-7. doi: 10.1016/j.annemergmed.2005.07.003. Epub 2005 Aug 18.</citation>
    <PMID>16387219</PMID>
  </reference>
  <reference>
    <citation>Chan EW, Taylor DM, Knott JC, Kong DC. Variation in the management of hypothetical cases of acute agitation in Australasian emergency departments. Emerg Med Australas. 2011 Feb;23(1):23-32. doi: 10.1111/j.1742-6723.2010.01348.x. Epub 2010 Nov 22.</citation>
    <PMID>21091874</PMID>
  </reference>
  <reference>
    <citation>Chan EW, Knott JC, Taylor DM, Phillips GA, Kong DC. Intravenous olanzapine--another option for the acutely agitated patient? Emerg Med Australas. 2009 Jun;21(3):241-2. doi: 10.1111/j.1742-6723.2009.01190.x. No abstract available.</citation>
    <PMID>19527287</PMID>
  </reference>
  <reference>
    <citation>Chan EW, Taylor DM, Knott JC, Liew D, Kong DC. The pharmacoeconomics of managing acute agitation in the emergency department: what do we know and how do we approach it? Expert Rev Pharmacoecon Outcomes Res. 2012 Oct;12(5):589-95. doi: 10.1586/erp.12.53.</citation>
    <PMID>23186399</PMID>
  </reference>
  <reference>
    <citation>Chan EW, Tang C, Lao KS, Ling Pong L, Tsui MS, Ho HF, Wong GC, Kong DC, McD Taylor D, Knott JC, Wong IC. Management of acute agitation in Hong Kong and comparisons with Australasia. Emerg Med Australas. 2015 Dec;27(6):542-548. doi: 10.1111/1742-6723.12499. Epub 2015 Dec 3.</citation>
    <PMID>26635127</PMID>
  </reference>
  <reference>
    <citation>Yap CYL, Taylor DM, Knott JC, Taylor SE, Phillips GA, Karro J, Chan EW, Kong DCM, Castle DJ. Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial. Addiction. 2017 Jul;112(7):1262-1269. doi: 10.1111/add.13780. Epub 2017 Feb 28.</citation>
    <PMID>28160494</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>November 3, 2022</last_update_submitted>
  <last_update_submitted_qc>November 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr. Esther Wai Yin Chan</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>emergency</keyword>
  <keyword>emergency medicine</keyword>
  <keyword>sedation</keyword>
  <keyword>acute agitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychomotor Agitation</mesh_term>
    <mesh_term>Emergencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diazepam</mesh_term>
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Olanzapine</mesh_term>
    <mesh_term>Haloperidol decanoate</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/NCT03246620
org study id: ChanEW oral sedation RCT
secondary id: 17111615
nct id: NCT03246620
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to determine whether oral olanzapine is safer (fewer adverse
      events) and more effective (shorter time to sedation) than conventional haloperidol or
      diazepam when used in the management of acute agitation in the emergency.
1. Investigate oral use of sedating drugs within a predominantly Chinese population, to
           address this void in international literature impacting the management of acute
           agitation.

        2. The multi-centre Randomised Clinical Trial will determine the safety and efficacy of
           oral olanzapine, in comparison with conventional medicines (haloperidol or diazepam) in
           a three-arm comparison for the sedation of acutely agitated patients in AEDs.
           Specifically, we aim to determine if administration of oral olanzapine (a)is more
           effective than sedation with oral haloperidol or oral diazepam alone; (b)is safer than
           sedation with comparison arms; (c)decreases the amount of subsequent redosing or
           alternative drugs required; (d)is more favourable than the haloperidol and diazepam arms
           with respect to safety, efficacy and adverse events.

      Investigate potential variables leading to AED attendance and/or admission requiring oral
      sedation. These may include patient demographic and regular medications and adherence.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time to achieve adequate sedation
time frame: Within 60 minutes from drug administration
description: Adequate sedation is determined by a 6-point validated scale
measure: Total study drug doses administered; alternative drugs and doses used
time frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
measure: Corrected QT interval (QTc)
time frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
measure: AED length of stay (LOS)
time frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
measure: Adverse events
time frame: From Accident & Emergency Department(AED) admission to transfer or discharge from AED, an expected average of 1 hour
description: including airway management (jaw thrust, oral, nasal airway), need for assisted ventilation (bag/mask, intubation), oxygen desaturation <90%, systolic BP<90 mmHg, dystonic reactions, seizures, vomiting or aspiration
arm group label: Olanzapine
arm group type: Experimental
description: oro-dispersible tablet (wafer)(Zyprexa), 5 mg, single dose
arm group label: Haloperidol
arm group type: Active Comparator
description: Haloperidol encapsulated tablet, 2 mg tablet, single dose
arm group label: Diazepam
arm group type: Active Comparator
description: Diazepam encapsulated tablet, 2mg tablet, single dose
intervention type: Drug
intervention name: Olanzapine oro-dispersible 5Mg Tab
description: Patient allocated to this arm will be given 5 mg olanzapine oro-dispersible tablet and an encapsulated placebo tablet
arm group label: Olanzapine
other name: Zyprexa
intervention type: Drug
intervention name: Haloperidol 2Mg encapsulated Tab
description: Patient allocated to this arm will be given 2 mg encapsulated haloperidol tablet and an oro-dispersible placebo tablet
arm group label: Haloperidol
intervention type: Drug
intervention name: Diazepam 2Mg encapsulated Tab
description: Patient allocated to this arm will be given 2 mg encapsulated diazepam tablet and an oro-dispersible placebo tablet
arm group label: Diazepam
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Hong Kong
citation: Knott JC, Bennett D, Rawet J, Taylor DM. Epidemiology of unarmed threats in the emergency department. Emerg Med Australas. 2005 Aug;17(4):351-8. doi: 10.1111/j.1742-6723.2005.00756.x.
PMID: 16091097
citation: Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013 Jan;61(1):72-81. doi: 10.1016/j.annemergmed.2012.07.118. Epub 2012 Sep 13.
PMID: 22981685
citation: Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med. 2006 Jan;47(1):61-7. doi: 10.1016/j.annemergmed.2005.07.003. Epub 2005 Aug 18.
PMID: 16387219
citation: Chan EW, Taylor DM, Knott JC, Kong DC. Variation in the management of hypothetical cases of acute agitation in Australasian emergency departments. Emerg Med Australas. 2011 Feb;23(1):23-32. doi: 10.1111/j.1742-6723.2010.01348.x. Epub 2010 Nov 22.
PMID: 21091874
citation: Chan EW, Knott JC, Taylor DM, Phillips GA, Kong DC. Intravenous olanzapine--another option for the acutely agitated patient? Emerg Med Australas. 2009 Jun;21(3):241-2. doi: 10.1111/j.1742-6723.2009.01190.x. No abstract available.
PMID: 19527287
citation: Chan EW, Taylor DM, Knott JC, Liew D, Kong DC. The pharmacoeconomics of managing acute agitation in the emergency department: what do we know and how do we approach it? Expert Rev Pharmacoecon Outcomes Res. 2012 Oct;12(5):589-95. doi: 10.1586/erp.12.53.
PMID: 23186399
citation: Chan EW, Tang C, Lao KS, Ling Pong L, Tsui MS, Ho HF, Wong GC, Kong DC, McD Taylor D, Knott JC, Wong IC. Management of acute agitation in Hong Kong and comparisons with Australasia. Emerg Med Australas. 2015 Dec;27(6):542-548. doi: 10.1111/1742-6723.12499. Epub 2015 Dec 3.
PMID: 26635127
citation: Yap CYL, Taylor DM, Knott JC, Taylor SE, Phillips GA, Karro J, Chan EW, Kong DCM, Castle DJ. Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial. Addiction. 2017 Jul;112(7):1262-1269. doi: 10.1111/add.13780. Epub 2017 Feb 28.
PMID: 28160494
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Dr. Esther Wai Yin Chan
investigator title: Associate Professor
mesh term: Psychomotor Agitation
mesh term: Emergencies
mesh term: Diazepam
mesh term: Haloperidol
mesh term: Olanzapine
mesh term: Haloperidol decanoate