<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/NCT02979626</url>
  </required_header>
  <id_info>
    <org_study_id>16-1785</org_study_id>
    <nct_id>NCT02979626</nct_id>
  </id_info>
  <brief_title>Evaluation of Moderate to Severe Influenza Outcomes in Children</brief_title>
  <acronym>M2SFlu</acronym>
  <official_title>Evaluation of Moderate to Severe Influenza Disease in Children 6 Months to 8 Years in Colorado</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was to determine whether moderate-severe endpoints (including high&#xD;
      fever, lower respiratory tract disease, acute otitis media, or serious extra-pulmonary&#xD;
      complications) were predictive of hospitalization, intensive care admission, antibiotic use&#xD;
      and other complications in children under 8 years of age.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective observational study aimed to determine the risk difference of&#xD;
      hospitalization due to moderate to severe influenza compared with mild influenza among&#xD;
      children aged 6 months to 8 years who were evaluated at Children's Hospital Colorado&#xD;
      emergency department and urgent care during the 2016-2017 influenza season. In addition, the&#xD;
      study intended to evaluate the risk difference for other health outcomes such as ICU&#xD;
      admission, antibiotic and antiviral use, caregiver and child absenteeism and recurrent (&gt;1)&#xD;
      healthcare visits, and to compare the healthcare costs associated with management of moderate&#xD;
      to severe versus mild influenza in children. Children who presented to Children's Hospital&#xD;
      Colorado Emergency Department (ED) and urgent care affiliated sites (North Campus urgent&#xD;
      care) with an influenza-like illness from December 2016 to April 2017 and during the&#xD;
      2016-2017 influenza season, were eligible for the study. Once enrolled in the study, the&#xD;
      investigators collected respiratory samples (nasal swab specimens) for influenza testing by&#xD;
      PCR, sociodemographic and clinical data including variables of interest outlined above, and&#xD;
      followed the clinical outcome of these children for 14 days after their initial presentation.&#xD;
      Some of the variables of interest the investigators collected are shown below.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 30, 2017</start_date>
  <completion_date type="Actual">May 5, 2018</completion_date>
  <primary_completion_date type="Actual">May 4, 2018</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Hospitalization</measure>
    <time_frame>0-14 days</time_frame>
    <description>Hospitalization within 14 days of influenza infection diagnosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU Admission</measure>
    <time_frame>0-14 days</time_frame>
    <description>Admission to the intensive care unit after influenza diagnosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral Use</measure>
    <time_frame>0-14 days</time_frame>
    <description>Antiviral use in children presenting to the ED or urgent care with influenza</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic Use</measure>
    <time_frame>0-14 days</time_frame>
    <description>Antibiotic use in children presenting to the ED or urgent care with influenza</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrent Visits</measure>
    <time_frame>0-14 days</time_frame>
    <description>Recurrent visits to the ED or healthcare provider in children presenting to the ED or urgent care with influenza</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>School Absenteeism</measure>
    <time_frame>0-14 days</time_frame>
    <description>Absenteeism from school or daycare in patients presenting to the ED or urgent care with influenza</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Work Absenteeism</measure>
    <time_frame>0-14 days</time_frame>
    <description>Absenteeism from work in caregivers of children presenting to the ED or urgent care with influenza</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Injectable Influenza Vaccine (IIV) Hospitalization</measure>
    <time_frame>0-14 days</time_frame>
    <description>Hospitalization among children who received IIV presenting to the ED or urgent care with influenza.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">1478</enrollment>
  <condition>Influenza</condition>
  <condition>Otitis Media</condition>
  <condition>Lower Resp Tract Infection</condition>
  <condition>Encephalitic Infection</condition>
  <condition>Myositis Viral</condition>
  <condition>Fever</condition>
  <arm_group>
    <arm_group_label>Moderate-to-severe Influenza</arm_group_label>
    <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mild Influenza</arm_group_label>
    <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Respiratory nasal swab</intervention_name>
    <description>Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
    <arm_group_label>Mild Influenza</arm_group_label>
    <arm_group_label>Moderate-to-severe Influenza</arm_group_label>
    <other_name>Nasal swab</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Respiratory swab samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children 6 months to 8 years of age and younger seeking evaluation and management of&#xD;
        influenza-like illness (ILI) at any of the study sites will be eligible for participation&#xD;
        in the study. The study will commence during the influenza season as determined by the&#xD;
        department of microbiology and epidemiology at CHCO (the influenza season commences when&#xD;
        there are 3 positive influenza PCR tests within a week), approximately from December 1,&#xD;
        2016 to April 30, 2017.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 6 months to &lt; 8 years&#xD;
&#xD;
          -  Presentation to one of the study sites with signs and symptoms of influenza-like&#xD;
             illness (temperature of &gt;37.8⁰C and at least one of the following: cough, sore throat,&#xD;
             runny nose or nasal congestion)&#xD;
&#xD;
          -  Parents or guardians agreeing and consenting to medical information release,&#xD;
             respiratory specimen collection and testing, email/phone call follow up and collection&#xD;
             of leftover blood samples obtained during routine clinical care&#xD;
&#xD;
          -  Patients seen during the 2016-2017 influenza season&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Respiratory symptom duration &gt; 14 days&#xD;
&#xD;
          -  Nurse only visit&#xD;
&#xD;
          -  Enrollment in the study within prior 14 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>8 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edwin J Asturias, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Suchitra Rao, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital North Campus Urgent Care</name>
      <address>
        <city>Broomfield</city>
        <state>Colorado</state>
        <zip>80023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wilkes JJ, Leckerman KH, Coffin SE, Keren R, Metjian TA, Hodinka RL, Zaoutis TE. Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza. J Pediatr. 2009 Mar;154(3):447-9. doi: 10.1016/j.jpeds.2008.09.026.</citation>
    <PMID>19874761</PMID>
  </reference>
  <reference>
    <citation>Coffin SE, Zaoutis TE, Rosenquist AB, Heydon K, Herrera G, Bridges CB, Watson B, Localio R, Hodinka RL, Keren R. Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics. 2007 Apr;119(4):740-8. doi: 10.1542/peds.2006-2679.</citation>
    <PMID>17403845</PMID>
  </reference>
  <reference>
    <citation>Izurieta HS, Thompson WW, Kramarz P, Shay DK, Davis RL, DeStefano F, Black S, Shinefield H, Fukuda K. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med. 2000 Jan 27;342(4):232-9. doi: 10.1056/NEJM200001273420402.</citation>
    <PMID>10648764</PMID>
  </reference>
  <reference>
    <citation>Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000 Jan 27;342(4):225-31. doi: 10.1056/NEJM200001273420401.</citation>
    <PMID>10648763</PMID>
  </reference>
  <reference>
    <citation>Salo H, Kilpi T, Sintonen H, Linna M, Peltola V, Heikkinen T. Cost-effectiveness of influenza vaccination of healthy children. Vaccine. 2006 Jun 5;24(23):4934-41. doi: 10.1016/j.vaccine.2006.03.057. Epub 2006 Apr 7.</citation>
    <PMID>16678945</PMID>
  </reference>
  <reference>
    <citation>Ferdinands JM, Olsho LE, Agan AA, Bhat N, Sullivan RM, Hall M, Mourani PM, Thompson M, Randolph AG; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012. J Infect Dis. 2014 Sep 1;210(5):674-83. doi: 10.1093/infdis/jiu185. Epub 2014 Mar 26.</citation>
    <PMID>24676207</PMID>
  </reference>
  <reference>
    <citation>Heikkinen T, Silvennoinen H, Heinonen S, Vuorinen T. Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children. Eur J Clin Microbiol Infect Dis. 2016 Jul;35(7):1107-13. doi: 10.1007/s10096-016-2641-9. Epub 2016 Apr 16.</citation>
    <PMID>27086364</PMID>
  </reference>
  <reference>
    <citation>Jain VK, Rivera L, Zaman K, Espos RA Jr, Sirivichayakul C, Quiambao BP, Rivera-Medina DM, Kerdpanich P, Ceyhan M, Dinleyici EC, Cravioto A, Yunus M, Chanthavanich P, Limkittikul K, Kurugol Z, Alhan E, Caplanusi A, Durviaux S, Boutet P, Ofori-Anyinam O, Chandrasekaran V, Dbaibo G, Innis BL. Vaccine for prevention of mild and moderate-to-severe influenza in children. N Engl J Med. 2013 Dec 26;369(26):2481-91. doi: 10.1056/NEJMoa1215817. Epub 2013 Dec 11.</citation>
    <PMID>24328444</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <results_first_submitted>September 3, 2019</results_first_submitted>
  <results_first_submitted_qc>January 15, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 4, 2021</results_first_posted>
  <last_update_submitted>January 15, 2021</last_update_submitted>
  <last_update_submitted_qc>January 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hospitalization</keyword>
  <keyword>intensive care unit</keyword>
  <keyword>school absenteeism</keyword>
  <keyword>work absenteeism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Myositis</mesh_term>
    <mesh_term>Otitis Media</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT02979626/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment occurred from January 30, 2017 until 5 May of 2018 including 2 influenza seasons at the Children's Hospital Colorado main Emergency Department and a peripheral Urgent Care Center</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Moderate-to-severe Influenza</title>
          <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
        </group>
        <group group_id="P2">
          <title>Mild Influenza</title>
          <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="313"/>
                <participants group_id="P2" count="98"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="313"/>
                <participants group_id="P2" count="98"/>
              </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>
      <population>Influenza positive ONLY</population>
      <group_list>
        <group group_id="B1">
          <title>Moderate-to-severe Influenza</title>
          <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
        </group>
        <group group_id="B2">
          <title>Mild Influenza</title>
          <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</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="313"/>
            <count group_id="B2" value="98"/>
            <count group_id="B3" value="411"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Subjects analyzed are ONLY influenza positive confirmed</population>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.8" spread="1.8"/>
                    <measurement group_id="B2" value="4.8" spread="2.4"/>
                    <measurement group_id="B3" value="4" spread="1.8"/>
                  </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="152"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="205"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="161"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="206"/>
                  </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="24"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="108"/>
                  </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="196"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="265"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Hospitalization</title>
        <description>Hospitalization within 14 days of influenza infection diagnosis</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>Hospitalization</title>
          <description>Hospitalization within 14 days of influenza infection diagnosis</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ICU Admission</title>
        <description>Admission to the intensive care unit after influenza diagnosis</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>ICU Admission</title>
          <description>Admission to the intensive care unit after influenza diagnosis</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Antiviral Use</title>
        <description>Antiviral use in children presenting to the ED or urgent care with influenza</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>Antiviral Use</title>
          <description>Antiviral use in children presenting to the ED or urgent care with influenza</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Antibiotic Use</title>
        <description>Antibiotic use in children presenting to the ED or urgent care with influenza</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>Antibiotic Use</title>
          <description>Antibiotic use in children presenting to the ED or urgent care with influenza</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Recurrent Visits</title>
        <description>Recurrent visits to the ED or healthcare provider in children presenting to the ED or urgent care with influenza</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>Recurrent Visits</title>
          <description>Recurrent visits to the ED or healthcare provider in children presenting to the ED or urgent care with influenza</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>School Absenteeism</title>
        <description>Absenteeism from school or daycare in patients presenting to the ED or urgent care with influenza</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>School Absenteeism</title>
          <description>Absenteeism from school or daycare in patients presenting to the ED or urgent care with influenza</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87"/>
                    <measurement group_id="O2" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Work Absenteeism</title>
        <description>Absenteeism from work in caregivers of children presenting to the ED or urgent care with influenza</description>
        <time_frame>0-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>Work Absenteeism</title>
          <description>Absenteeism from work in caregivers of children presenting to the ED or urgent care with influenza</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="313"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71"/>
                    <measurement group_id="O2" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Injectable Influenza Vaccine (IIV) Hospitalization</title>
        <description>Hospitalization among children who received IIV presenting to the ED or urgent care with influenza.</description>
        <time_frame>0-14 days</time_frame>
        <population>Outcome measure data is not required to be reported for this &quot;other pre-specified&quot; (not primary or secondary) outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate-to-severe Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
          <group group_id="O2">
            <title>Mild Influenza</title>
            <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
          </group>
        </group_list>
        <measure>
          <title>Injectable Influenza Vaccine (IIV) Hospitalization</title>
          <description>Hospitalization among children who received IIV presenting to the ED or urgent care with influenza.</description>
          <population>Outcome measure data is not required to be reported for this &quot;other pre-specified&quot; (not primary or secondary) outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>14 days since enrollment until follow up</time_frame>
      <desc>Procedure related adverse events (nasal bleeding, nasal trauma from swab)</desc>
      <group_list>
        <group group_id="E1">
          <title>Moderate-to-severe Influenza</title>
          <description>Children 6 weeks to 8 years of age with influenza-like illness and one of the following:&#xD;
Fever &gt;39&#xD;
Lower respiratory tract infection&#xD;
Acute otitis media&#xD;
Serious extra-pulmonary manifestations (myositis, encephalitis)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</description>
        </group>
        <group group_id="E2">
          <title>Mild Influenza</title>
          <description>Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)&#xD;
Respiratory nasal swab: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.</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="313"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="313"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="313"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </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>Dr. Suchitra Rao</name_or_title>
      <organization>University of Colorado Denver</organization>
      <phone>7207771234</phone>
      <email>suchitra.rao@childrenscolorado.org</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/NCT02979626
org study id: 16-1785
nct id: NCT02979626
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study was to determine whether moderate-severe endpoints (including high
      fever, lower respiratory tract disease, acute otitis media, or serious extra-pulmonary
      complications) were predictive of hospitalization, intensive care admission, antibiotic use
      and other complications in children under 8 years of age.
This prospective observational study aimed to determine the risk difference of
      hospitalization due to moderate to severe influenza compared with mild influenza among
      children aged 6 months to 8 years who were evaluated at Children's Hospital Colorado
      emergency department and urgent care during the 2016-2017 influenza season. In addition, the
      study intended to evaluate the risk difference for other health outcomes such as ICU
      admission, antibiotic and antiviral use, caregiver and child absenteeism and recurrent (>1)
      healthcare visits, and to compare the healthcare costs associated with management of moderate
      to severe versus mild influenza in children. Children who presented to Children's Hospital
      Colorado Emergency Department (ED) and urgent care affiliated sites (North Campus urgent
      care) with an influenza-like illness from December 2016 to April 2017 and during the
      2016-2017 influenza season, were eligible for the study. Once enrolled in the study, the
      investigators collected respiratory samples (nasal swab specimens) for influenza testing by
      PCR, sociodemographic and clinical data including variables of interest outlined above, and
      followed the clinical outcome of these children for 14 days after their initial presentation.
      Some of the variables of interest the investigators collected are shown below.
observational model: Cohort
time perspective: Cross-Sectional
measure: Hospitalization
time frame: 0-14 days
description: Hospitalization within 14 days of influenza infection diagnosis
measure: ICU Admission
time frame: 0-14 days
description: Admission to the intensive care unit after influenza diagnosis
measure: Antiviral Use
time frame: 0-14 days
description: Antiviral use in children presenting to the ED or urgent care with influenza
measure: Antibiotic Use
time frame: 0-14 days
description: Antibiotic use in children presenting to the ED or urgent care with influenza
measure: Recurrent Visits
time frame: 0-14 days
description: Recurrent visits to the ED or healthcare provider in children presenting to the ED or urgent care with influenza
measure: School Absenteeism
time frame: 0-14 days
description: Absenteeism from school or daycare in patients presenting to the ED or urgent care with influenza
measure: Work Absenteeism
time frame: 0-14 days
description: Absenteeism from work in caregivers of children presenting to the ED or urgent care with influenza
measure: Injectable Influenza Vaccine (IIV) Hospitalization
time frame: 0-14 days
description: Hospitalization among children who received IIV presenting to the ED or urgent care with influenza.
arm group label: Moderate-to-severe Influenza
description: Children 6 weeks to 8 years of age with influenza-like illness and one of the following:
Fever >39
Lower respiratory tract infection
Acute otitis media
Serious extra-pulmonary manifestations (myositis, encephalitis)
arm group label: Mild Influenza
description: Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)
intervention type: Procedure
intervention name: Respiratory nasal swab
description: Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.
arm group label: Mild Influenza
arm group label: Moderate-to-severe Influenza
other name: Nasal swab
Respiratory swab samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Months
maximum age: 8 Years
healthy volunteers: No
last name: Edwin J Asturias, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Suchitra Rao, MD
role: Study Director
affiliation: University of Colorado, Denver
facility: 
facility: 
country: United States
citation: Wilkes JJ, Leckerman KH, Coffin SE, Keren R, Metjian TA, Hodinka RL, Zaoutis TE. Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza. J Pediatr. 2009 Mar;154(3):447-9. doi: 10.1016/j.jpeds.2008.09.026.
PMID: 19874761
citation: Coffin SE, Zaoutis TE, Rosenquist AB, Heydon K, Herrera G, Bridges CB, Watson B, Localio R, Hodinka RL, Keren R. Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics. 2007 Apr;119(4):740-8. doi: 10.1542/peds.2006-2679.
PMID: 17403845
citation: Izurieta HS, Thompson WW, Kramarz P, Shay DK, Davis RL, DeStefano F, Black S, Shinefield H, Fukuda K. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med. 2000 Jan 27;342(4):232-9. doi: 10.1056/NEJM200001273420402.
PMID: 10648764
citation: Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000 Jan 27;342(4):225-31. doi: 10.1056/NEJM200001273420401.
PMID: 10648763
citation: Salo H, Kilpi T, Sintonen H, Linna M, Peltola V, Heikkinen T. Cost-effectiveness of influenza vaccination of healthy children. Vaccine. 2006 Jun 5;24(23):4934-41. doi: 10.1016/j.vaccine.2006.03.057. Epub 2006 Apr 7.
PMID: 16678945
citation: Ferdinands JM, Olsho LE, Agan AA, Bhat N, Sullivan RM, Hall M, Mourani PM, Thompson M, Randolph AG; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012. J Infect Dis. 2014 Sep 1;210(5):674-83. doi: 10.1093/infdis/jiu185. Epub 2014 Mar 26.
PMID: 24676207
citation: Heikkinen T, Silvennoinen H, Heinonen S, Vuorinen T. Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children. Eur J Clin Microbiol Infect Dis. 2016 Jul;35(7):1107-13. doi: 10.1007/s10096-016-2641-9. Epub 2016 Apr 16.
PMID: 27086364
citation: Jain VK, Rivera L, Zaman K, Espos RA Jr, Sirivichayakul C, Quiambao BP, Rivera-Medina DM, Kerdpanich P, Ceyhan M, Dinleyici EC, Cravioto A, Yunus M, Chanthavanich P, Limkittikul K, Kurugol Z, Alhan E, Caplanusi A, Durviaux S, Boutet P, Ofori-Anyinam O, Chandrasekaran V, Dbaibo G, Innis BL. Vaccine for prevention of mild and moderate-to-severe influenza in children. N Engl J Med. 2013 Dec 26;369(26):2481-91. doi: 10.1056/NEJMoa1215817. Epub 2013 Dec 11.
PMID: 24328444
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Influenza, Human
mesh term: Myositis
mesh term: Otitis Media
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 