<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/NCT03043430</url>
  </required_header>
  <id_info>
    <org_study_id>C.2016.021</org_study_id>
    <nct_id>NCT03043430</nct_id>
  </id_info>
  <brief_title>Intranasal Ketamine for Anxiolysis in Pediatric Emergency Department Patients</brief_title>
  <official_title>Anxiolysis for Emergency Department Procedures in Pediatric Patients Using Intranasal Ketamine Compared With Intranasal Midazolam: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brooke Army Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brooke Army Medical Center</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>
      Investigators plan to conduct a randomized, double-blinded, controlled study among pediatric&#xD;
      patients requiring minor procedures in the Emergency Department setting. Patients will be&#xD;
      randomized to one of two arms of intranasal treatments: ketamine 1.0 mg/kg (K) or midazolam&#xD;
      0.3 mg/kg (M). The primary outcome will be change in anxiety using the Modified Yale&#xD;
      Preoperative Anxiety Scale (mYPAS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The intranasal route of drug delivery is commonly used in Emergency Departments (ED) in&#xD;
      pediatric patients. Multiple trials have shown the safety of administration of intranasal&#xD;
      ketamine, including studies performed in the ED to treat pain in pediatric patients. The use&#xD;
      of ketamine for anxiolysis has not been directly studied; however, ketamine has been shown to&#xD;
      have anxiolytic effect at low doses as secondary outcomes when studied. Midazolam has been&#xD;
      established as an effective medication to provide analgesia and anxiolysis. Investigators&#xD;
      plan to conduct a randomized, double-blinded, controlled study in the Emergency Department.&#xD;
      Pediatric patients presenting to the ED with the need for minor procedures who meet the&#xD;
      inclusion and exclusion criteria will be consented, and if amenable, will be enrolled.&#xD;
      Patients will be randomized to one of two arms of intranasal treatments: ketamine 1.0 mg/kg&#xD;
      (K) or midazolam 0.3 mg/kg (M). Patients will be tracked for symptom improvement within the&#xD;
      Emergency Department. The primary outcome will be change in anxiety from initial measurement&#xD;
      to measurement 5 minutes pre-procedure using the Modified Yale Preoperative Anxiety Scale&#xD;
      (mYPAS). Secondary outcomes will include sedation level, adverse events, need for additional&#xD;
      medications, change in pain rating, patient and/or parent/guardian satisfaction.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Research manpower shortage&#xD;
  </why_stopped>
  <start_date type="Actual">May 2016</start_date>
  <completion_date type="Actual">April 2023</completion_date>
  <primary_completion_date type="Actual">April 2023</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>
    <intervention_model_description>Subjects will be randomized to one of two treatment arms.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Medication (ketamine versus midazolam) will be drawn up in unmarked syringe and applied to the patient by mucosal atomization device by a nurse not directly involved in the investigation or the patient's care.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in mYPAS</measure>
    <time_frame>Change in score between initial measurement versus 5 minutes pre-procedure</time_frame>
    <description>Modified Yale preoperative anxiety scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in sedation scale</measure>
    <time_frame>Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge</time_frame>
    <description>University of Michigan sedation scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pain rating (Wong-Baker Pain Faces Rating Scale)</measure>
    <time_frame>Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge</time_frame>
    <description>Wong-Baker Pain Faces Rating Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in anxiety score (Visual analogue scale)</measure>
    <time_frame>Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge</time_frame>
    <description>Visual analogue scale</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Anxiety</condition>
  <condition>Pediatric ALL</condition>
  <condition>Procedural Anxiety</condition>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ketamine 100 mg/mL concentration administered in a single 1.0 mg/kg dose with a maximum of 50mg intranasal via mucosal atomization device.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Midazolam 5 mg/mL concentration administered in a single administered in a single 0.3 mg/kg dose with a maximum of 5mg intranasal via mucosal atomization device.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine 100 MG/ML</intervention_name>
    <description>Administer ketamine via mucosal atomization device</description>
    <arm_group_label>Ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam 5 MG/ML</intervention_name>
    <description>Administer midazolam via mucosal atomization device</description>
    <arm_group_label>Midazolam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients age 2 to 12 years who present to the ED&#xD;
&#xD;
          -  Requiring intravenous access&#xD;
&#xD;
          -  Requiring laceration repairs&#xD;
&#xD;
          -  Requiring incision and drainage of abscesses&#xD;
&#xD;
          -  Requiring digital nerve blocks&#xD;
&#xD;
          -  Requiring radiological imaging&#xD;
&#xD;
          -  Requiring bladder catheterization&#xD;
&#xD;
          -  Requiring foreign body removal.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Vital sign abnormalities greater than 20% deviation from age-normalized ranges&#xD;
&#xD;
          -  Altered mental status/delirium or intoxication&#xD;
&#xD;
          -  Patient or patient's parent/guardian are unwilling to participate or provide informed&#xD;
             consent&#xD;
&#xD;
          -  Any allergy to ketamine or midazolam&#xD;
&#xD;
          -  Patient is female with history of menarche&#xD;
&#xD;
          -  Presence of chronic oxygen-dependent pulmonary disease, liver cirrhosis, or renal&#xD;
             disease requiring dialysis&#xD;
&#xD;
          -  Presence of ischemic heart disease, heart failure, or a history of unstable&#xD;
             dysrhythmias&#xD;
&#xD;
          -  Presence of intracranial mass or vascular lesion.&#xD;
&#xD;
          -  Presence of a history of psychosis or hallucinations&#xD;
&#xD;
          -  Weight greater than 100kg&#xD;
&#xD;
          -  History of increased intracranial pressure/ hypertensive hydrocephalus within the last&#xD;
             3 months&#xD;
&#xD;
          -  Non-English speaking/reading parent/guardian and/or patients&#xD;
&#xD;
          -  Patient is acutely psychotic&#xD;
&#xD;
          -  Provider feels that patient currently or likely will require chemical and/or physical&#xD;
             restraints&#xD;
&#xD;
          -  History of prolonged QT-interval&#xD;
&#xD;
          -  Nasal trauma&#xD;
&#xD;
          -  Epistaxis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nadia M Pearson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty Physician</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>San Antonio Military Medical Center</name>
      <address>
        <city>Fort Sam Houston</city>
        <state>Texas</state>
        <zip>78234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hosseini Jahromi SA, Hosseini Valami SM, Adeli N, Yazdi Z. Comparison of the effects of intranasal midazolam versus different doses of intranasal ketamine on reducing preoperative pediatric anxiety: a prospective randomized clinical trial. J Anesth. 2012 Dec;26(6):878-82. doi: 10.1007/s00540-012-1422-6. Epub 2012 Jun 12.</citation>
    <PMID>22688444</PMID>
  </reference>
  <reference>
    <citation>Roelofse JA, Shipton EA, de la Harpe CJ, Blignaut RJ. Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison. Anesth Prog. 2004;51(4):114-21.</citation>
    <PMID>15675259</PMID>
  </reference>
  <reference>
    <citation>Narendra PL, Naphade RW, Nallamilli S, Mohd S. A comparison of intranasal ketamine and intranasal midazolam for pediatric premedication. Anesth Essays Res. 2015 May-Aug;9(2):213-8. doi: 10.4103/0259-1162.154051.</citation>
    <PMID>26417129</PMID>
  </reference>
  <reference>
    <citation>Khatavkar SS, Bakhshi RG. Comparison of nasal Midazolam with Ketamine versus nasal Midazolam as a premedication in children. Saudi J Anaesth. 2014 Jan;8(1):17-21. doi: 10.4103/1658-354X.125904.</citation>
    <PMID>24665234</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <last_update_submitted>April 23, 2023</last_update_submitted>
  <last_update_submitted_qc>April 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brooke Army Medical Center</investigator_affiliation>
    <investigator_full_name>Michael D. April</investigator_full_name>
    <investigator_title>Assistant Program Director for Research, EM Residency</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Emergencies</mesh_term>
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Ketamine</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/NCT03043430
org study id: C.2016.021
nct id: NCT03043430
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Investigators plan to conduct a randomized, double-blinded, controlled study among pediatric
      patients requiring minor procedures in the Emergency Department setting. Patients will be
      randomized to one of two arms of intranasal treatments: ketamine 1.0 mg/kg (K) or midazolam
      0.3 mg/kg (M). The primary outcome will be change in anxiety using the Modified Yale
      Preoperative Anxiety Scale (mYPAS).
The intranasal route of drug delivery is commonly used in Emergency Departments (ED) in
      pediatric patients. Multiple trials have shown the safety of administration of intranasal
      ketamine, including studies performed in the ED to treat pain in pediatric patients. The use
      of ketamine for anxiolysis has not been directly studied; however, ketamine has been shown to
      have anxiolytic effect at low doses as secondary outcomes when studied. Midazolam has been
      established as an effective medication to provide analgesia and anxiolysis. Investigators
      plan to conduct a randomized, double-blinded, controlled study in the Emergency Department.
      Pediatric patients presenting to the ED with the need for minor procedures who meet the
      inclusion and exclusion criteria will be consented, and if amenable, will be enrolled.
      Patients will be randomized to one of two arms of intranasal treatments: ketamine 1.0 mg/kg
      (K) or midazolam 0.3 mg/kg (M). Patients will be tracked for symptom improvement within the
      Emergency Department. The primary outcome will be change in anxiety from initial measurement
      to measurement 5 minutes pre-procedure using the Modified Yale Preoperative Anxiety Scale
      (mYPAS). Secondary outcomes will include sedation level, adverse events, need for additional
      medications, change in pain rating, patient and/or parent/guardian satisfaction.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be randomized to one of two treatment arms.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Medication (ketamine versus midazolam) will be drawn up in unmarked syringe and applied to the patient by mucosal atomization device by a nurse not directly involved in the investigation or the patient's care.
measure: Change in mYPAS
time frame: Change in score between initial measurement versus 5 minutes pre-procedure
description: Modified Yale preoperative anxiety scale
measure: Change in sedation scale
time frame: Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge
description: University of Michigan sedation scale
measure: Change in pain rating (Wong-Baker Pain Faces Rating Scale)
time frame: Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge
description: Wong-Baker Pain Faces Rating Scale
measure: Change in anxiety score (Visual analogue scale)
time frame: Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge
description: Visual analogue scale
arm group label: Ketamine
arm group type: Experimental
description: Ketamine 100 mg/mL concentration administered in a single 1.0 mg/kg dose with a maximum of 50mg intranasal via mucosal atomization device.
arm group label: Midazolam
arm group type: Active Comparator
description: Midazolam 5 mg/mL concentration administered in a single administered in a single 0.3 mg/kg dose with a maximum of 5mg intranasal via mucosal atomization device.
intervention type: Drug
intervention name: Ketamine 100 MG/ML
description: Administer ketamine via mucosal atomization device
arm group label: Ketamine
intervention type: Drug
intervention name: Midazolam 5 MG/ML
description: Administer midazolam via mucosal atomization device
arm group label: Midazolam
criteria: 
gender: All
minimum age: 2 Years
maximum age: 12 Years
healthy volunteers: No
last name: Nadia M Pearson, MD
role: Principal Investigator
affiliation: Faculty Physician
facility: 
country: United States
citation: Hosseini Jahromi SA, Hosseini Valami SM, Adeli N, Yazdi Z. Comparison of the effects of intranasal midazolam versus different doses of intranasal ketamine on reducing preoperative pediatric anxiety: a prospective randomized clinical trial. J Anesth. 2012 Dec;26(6):878-82. doi: 10.1007/s00540-012-1422-6. Epub 2012 Jun 12.
PMID: 22688444
citation: Roelofse JA, Shipton EA, de la Harpe CJ, Blignaut RJ. Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison. Anesth Prog. 2004;51(4):114-21.
PMID: 15675259
citation: Narendra PL, Naphade RW, Nallamilli S, Mohd S. A comparison of intranasal ketamine and intranasal midazolam for pediatric premedication. Anesth Essays Res. 2015 May-Aug;9(2):213-8. doi: 10.4103/0259-1162.154051.
PMID: 26417129
citation: Khatavkar SS, Bakhshi RG. Comparison of nasal Midazolam with Ketamine versus nasal Midazolam as a premedication in children. Saudi J Anaesth. 2014 Jan;8(1):17-21. doi: 10.4103/1658-354X.125904.
PMID: 24665234
responsible party type: Principal Investigator
investigator affiliation: Brooke Army Medical Center
investigator full name: Michael D. April
investigator title: Assistant Program Director for Research, EM Residency
mesh term: Emergencies
mesh term: Anxiety Disorders
mesh term: Midazolam
mesh term: Ketamine
sharing ipd: No