<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/NCT03781817</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-300002731</org_study_id>
    <nct_id>NCT03781817</nct_id>
  </id_info>
  <brief_title>Intranasal Versus Intravenous Ketamine for Procedural Sedation in Children With Non-operative Fractures</brief_title>
  <official_title>Intranasal Versus Intravenous Ketamine for Procedural Sedation in Children With Non-operative Fractures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alabama at Birmingham</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This a randomized clinical trial involving children with non-operative fractures presenting&#xD;
      the emergency department randomized either to intranasal or intravenous ketamine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to determine if Intranasal Ketamine (INK) is efficacious for&#xD;
      Procedural Sedation and Analgesia (PSA) when compared to Intravenous Ketamine (IVK) in&#xD;
      children with non-operative fractures. The primary aim is to determine if INK provides&#xD;
      non-inferior sedation to IVK as defined by a Modified Ramsay Sedation score of ≥ 4 and also&#xD;
      to compare the proportion of successful procedure between two treatment groups. The secondary&#xD;
      aim is to compare proportion of adverse events and compare duration of sedation and length of&#xD;
      emergency department (ED) stay between treatment groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Transition/change of primary investigators&#xD;
  </why_stopped>
  <start_date type="Actual">September 9, 2019</start_date>
  <completion_date type="Actual">April 30, 2022</completion_date>
  <primary_completion_date type="Actual">January 21, 2022</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Achieved Adequate Sedation.</measure>
    <time_frame>Induction up to 10 minutes</time_frame>
    <description>Determine if IN ketamine provides non-inferior sedation to IV ketamine as defined by a Modified Ramsay Sedation score of ≥ 4. Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 4 or greater is set to be satisfactory for deep sedation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Adequately Sedated Participants Successfully Completing the Procedure Without Requiring Rescue Medications.</measure>
    <time_frame>From induction to discharge from sedation by emergency physician, up to 3 hours.</time_frame>
    <description>Rescue medication is defined as requiring additional doses of Ketamine to maintain adequate sedation. Successful procedure completion will be define as completing the procedure with only the induction dose and without requiring rescue medications.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Non-serious Adverse Events.</measure>
    <time_frame>From induction to discharge from the emergency department.</time_frame>
    <description>Non-serious adverse events include allergic reaction, vomiting, emergence agitation, and oxygen desaturations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Sedation Using Modified Ramsay Sedation Scale.</measure>
    <time_frame>From induction to discharge from sedation by the emergency physician.</time_frame>
    <description>Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 2 or less is set to be satisfactory for discharge from sedation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Emergency Department Stay.</measure>
    <time_frame>From arrival to emergency department to discharge order entered by emergency physician.</time_frame>
    <description>Measured from time of arrival to emergency department to discharge order.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Trauma</condition>
  <condition>Fractures, Closed</condition>
  <condition>Children, Only</condition>
  <condition>Deep Sedation</condition>
  <condition>Ketamine</condition>
  <arm_group>
    <arm_group_label>Intravenous ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intranasal ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous Ketamine</intervention_name>
    <description>Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
    <arm_group_label>Intravenous ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intranasal Ketamine</intervention_name>
    <description>Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
    <arm_group_label>Intranasal ketamine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children 1-18 years of age.&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) I or II&#xD;
&#xD;
          -  Non-operative fracture requiring reduction&#xD;
&#xD;
          -  Body weight less than or equal to 25 kg as measured by standard weighing scale&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ASA classification III or above&#xD;
&#xD;
          -  Age less than 1 year&#xD;
&#xD;
          -  History of hypertension, known coronary artery disease or Kawasaki disease, congestive&#xD;
             heart failure, acute glaucoma or globe injury, increased intracranial pressure or&#xD;
             intracranial mass lesion, acute porphyria, developmental delays, or major psychiatric&#xD;
             disorder&#xD;
&#xD;
          -  Prior allergy to ketamine&#xD;
&#xD;
          -  Unavailable parent or guardian to provide consent&#xD;
&#xD;
          -  Non-English speaking&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James Statler, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Judson Barber, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <results_first_submitted>January 18, 2023</results_first_submitted>
  <results_first_submitted_qc>April 19, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 20, 2023</results_first_posted>
  <last_update_submitted>April 19, 2023</last_update_submitted>
  <last_update_submitted_qc>April 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>James Statler</investigator_full_name>
    <investigator_title>Pediatric Emergency Medicine Fellow</investigator_title>
  </responsible_party>
  <keyword>procedural sedation</keyword>
  <keyword>ketamine</keyword>
  <keyword>pediatric</keyword>
  <keyword>fracture</keyword>
  <keyword>intranasal</keyword>
  <keyword>intravenous</keyword>
  <keyword>emergency department</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Fractures, Closed</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03781817/Prot_SAP_ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patient screening, enrollment and informed consent will be obtained in the emergency department (ED) of Children's of Alabama (COA). Data collection will take place in the ED as well as in Children's Park Place, Suite 110. The remainder of the research, including data analysis, and collaboration amongst the principal investigator and the sub-investigators, will be conducted in Children's Park Place, Suite 110.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Intravenous Ketamine</title>
          <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
        </group>
        <group group_id="P2">
          <title>Intranasal Ketamine</title>
          <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intravenous Ketamine</title>
          <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
        </group>
        <group group_id="B2">
          <title>Intranasal Ketamine</title>
          <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="17"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5" spread="1.65"/>
                    <measurement group_id="B2" value="5" spread="1.99"/>
                    <measurement group_id="B3" value="5" spread="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Allergies</title>
          <description>Whether participants have any previous known medication allergies.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>weight in kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18.1" spread="3.2"/>
                    <measurement group_id="B2" value="18.4" spread="4.13"/>
                    <measurement group_id="B3" value="18.15" spread="3.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History</title>
          <description>Whether participants have any known previous medical history.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Surgical History</title>
          <description>Whether participants have any previous surgical history.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Achieved Adequate Sedation.</title>
        <description>Determine if IN ketamine provides non-inferior sedation to IV ketamine as defined by a Modified Ramsay Sedation score of ≥ 4. Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 4 or greater is set to be satisfactory for deep sedation.</description>
        <time_frame>Induction up to 10 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Ketamine</title>
            <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
          <group group_id="O2">
            <title>Intranasal Ketamine</title>
            <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Achieved Adequate Sedation.</title>
          <description>Determine if IN ketamine provides non-inferior sedation to IV ketamine as defined by a Modified Ramsay Sedation score of ≥ 4. Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 4 or greater is set to be satisfactory for deep sedation.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Adequately Sedated Participants Successfully Completing the Procedure Without Requiring Rescue Medications.</title>
        <description>Rescue medication is defined as requiring additional doses of Ketamine to maintain adequate sedation. Successful procedure completion will be define as completing the procedure with only the induction dose and without requiring rescue medications.</description>
        <time_frame>From induction to discharge from sedation by emergency physician, up to 3 hours.</time_frame>
        <population>Number of participants that required rescue dosing either due to inadequate sedation at 10 minutes or after adequate sedation at 10 minutes but requiring more sedation to complete the procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Ketamine</title>
            <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
          <group group_id="O2">
            <title>Intranasal Ketamine</title>
            <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Adequately Sedated Participants Successfully Completing the Procedure Without Requiring Rescue Medications.</title>
          <description>Rescue medication is defined as requiring additional doses of Ketamine to maintain adequate sedation. Successful procedure completion will be define as completing the procedure with only the induction dose and without requiring rescue medications.</description>
          <population>Number of participants that required rescue dosing either due to inadequate sedation at 10 minutes or after adequate sedation at 10 minutes but requiring more sedation to complete the procedure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Non-serious Adverse Events.</title>
        <description>Non-serious adverse events include allergic reaction, vomiting, emergence agitation, and oxygen desaturations.</description>
        <time_frame>From induction to discharge from the emergency department.</time_frame>
        <population>Percentage of participants that experienced any possible adverse events from sedation with either intravenous or intranasal ketamine.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Ketamine</title>
            <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
          <group group_id="O2">
            <title>Intranasal Ketamine</title>
            <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Non-serious Adverse Events.</title>
          <description>Non-serious adverse events include allergic reaction, vomiting, emergence agitation, and oxygen desaturations.</description>
          <population>Percentage of participants that experienced any possible adverse events from sedation with either intravenous or intranasal ketamine.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Sedation Using Modified Ramsay Sedation Scale.</title>
        <description>Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 2 or less is set to be satisfactory for discharge from sedation.</description>
        <time_frame>From induction to discharge from sedation by the emergency physician.</time_frame>
        <population>Describes the duration of sedation (in minutes) from the start of induction to when participant was discharged from sedation by the emergency physician.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Ketamine</title>
            <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
          <group group_id="O2">
            <title>Intranasal Ketamine</title>
            <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Sedation Using Modified Ramsay Sedation Scale.</title>
          <description>Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 2 or less is set to be satisfactory for discharge from sedation.</description>
          <population>Describes the duration of sedation (in minutes) from the start of induction to when participant was discharged from sedation by the emergency physician.</population>
          <units>Minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.71" spread="32.54"/>
                    <measurement group_id="O2" value="101.21" spread="52.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Emergency Department Stay.</title>
        <description>Measured from time of arrival to emergency department to discharge order.</description>
        <time_frame>From arrival to emergency department to discharge order entered by emergency physician.</time_frame>
        <population>Duration of total emergency department stay from arrival to the emergency department to discharge order entered by emergency physician.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Ketamine</title>
            <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
          <group group_id="O2">
            <title>Intranasal Ketamine</title>
            <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Emergency Department Stay.</title>
          <description>Measured from time of arrival to emergency department to discharge order.</description>
          <population>Duration of total emergency department stay from arrival to the emergency department to discharge order entered by emergency physician.</population>
          <units>Time (in minutes)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="325.65" spread="104.7"/>
                    <measurement group_id="O2" value="312.4" spread="67.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time the induction medication (either intranasal ketamine or intranasal hypertonic saline) to discharge order by the emergency physician, up to 6 hours.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intravenous Ketamine</title>
          <description>Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.&#xD;
Intravenous Ketamine: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
        </group>
        <group group_id="E2">
          <title>Intranasal Ketamine</title>
          <description>Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.&#xD;
Intranasal Ketamine: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>Vomiting after the conclusion of the sedation and procedure not including nausea.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>James Statler, MD</name_or_title>
      <organization>University of Alabama at Birmingham, Department of Pediatrics</organization>
      <phone>(205) 638-6048</phone>
      <email>jstatler@uabmc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03781817
org study id: IRB-300002731
nct id: NCT03781817
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This a randomized clinical trial involving children with non-operative fractures presenting
      the emergency department randomized either to intranasal or intravenous ketamine.
The purpose of this study is to determine if Intranasal Ketamine (INK) is efficacious for
      Procedural Sedation and Analgesia (PSA) when compared to Intravenous Ketamine (IVK) in
      children with non-operative fractures. The primary aim is to determine if INK provides
      non-inferior sedation to IVK as defined by a Modified Ramsay Sedation score of ≥ 4 and also
      to compare the proportion of successful procedure between two treatment groups. The secondary
      aim is to compare proportion of adverse events and compare duration of sedation and length of
      emergency department (ED) stay between treatment groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants Who Achieved Adequate Sedation.
time frame: Induction up to 10 minutes
description: Determine if IN ketamine provides non-inferior sedation to IV ketamine as defined by a Modified Ramsay Sedation score of ≥ 4. Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 4 or greater is set to be satisfactory for deep sedation.
measure: Percentage of Adequately Sedated Participants Successfully Completing the Procedure Without Requiring Rescue Medications.
time frame: From induction to discharge from sedation by emergency physician, up to 3 hours.
description: Rescue medication is defined as requiring additional doses of Ketamine to maintain adequate sedation. Successful procedure completion will be define as completing the procedure with only the induction dose and without requiring rescue medications.
measure: Percentage of Participants With Non-serious Adverse Events.
time frame: From induction to discharge from the emergency department.
description: Non-serious adverse events include allergic reaction, vomiting, emergence agitation, and oxygen desaturations.
measure: Duration of Sedation Using Modified Ramsay Sedation Scale.
time frame: From induction to discharge from sedation by the emergency physician.
description: Modified Ramsay Sedation scale is used to evaluate levels of sedation. The scale range is from 0 to 6 with a higher score indicated deeper levels of sedation. At levels of 2 or less is set to be satisfactory for discharge from sedation.
measure: Duration of Emergency Department Stay.
time frame: From arrival to emergency department to discharge order entered by emergency physician.
description: Measured from time of arrival to emergency department to discharge order.
arm group label: Intravenous ketamine
arm group type: Active Comparator
description: Participants randomized to IV ketamine will be receive IV ketamine and Intranasal normal saline.
arm group label: Intranasal ketamine
arm group type: Experimental
description: Participants randomized to Intranasal Ketamine group will receive Intranasal ketamine and IV normal saline.
intervention type: Drug
intervention name: Intravenous Ketamine
description: Subject randomized to IV Ketamine arm will receive IN Normal Saline at induction. After 8 minutes subjects will receive IV Ketamine (10 mg/mL) at a dose of 1.5 mg/kg. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.
arm group label: Intravenous ketamine
intervention type: Drug
intervention name: Intranasal Ketamine
description: Subject randomized to IN Ketamine arm will receive IN Ketamine (100 mg/mL) at a dose of 9 mg/kg at induction. After 8 minutes subjects will receive IV Normal Saline. Level of sedation will be scored at the 15 minutes from induction to determine if adequate sedation has been achieved.
arm group label: Intranasal ketamine
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: James Statler, MD
role: Study Chair
affiliation: Emory University
last name: Judson Barber, MD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: James Statler
investigator title: Pediatric Emergency Medicine Fellow
mesh term: Fractures, Bone
mesh term: Fractures, Closed
mesh term: Ketamine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 