<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/NCT02212990</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00056213</org_study_id>
    <secondary_id>200-2012-53663</secondary_id>
    <nct_id>NCT02212990</nct_id>
  </id_info>
  <brief_title>The Effect of Prophylactic Antipyretics on Immune Responses and Fever After 2014-2015 and 2015-2016 Inactivated Influenza Vaccine</brief_title>
  <official_title>Clinical Immunization Safety Assessment (CISA): A Study to Assess the Effect of Prophylactic Antipyretics on Immune Responses and Fever After 2014-2015 and 2015-2016 Inactivated Influenza Vaccine (IIV) Administered to Children 6 Through 47 Months of Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to conduct a double-blind, placebo-controlled study to assess the effect of&#xD;
      prophylactic antipyretics on the immune responses and rates of fever after inactivated&#xD;
      influenza vaccine (IIV) in children 6 through 47 months of age.&#xD;
&#xD;
      In this study, 160 healthy children, 6 through 47 months of age, including some children at&#xD;
      risk of febrile seizure, will be randomized to one of three different treatment arms.&#xD;
      Children will receive either blinded therapy with prophylactic acetaminophen or placebo&#xD;
      immediately following and every 4 to 6 hours in the 24 hours after receipt of a dose of IIV&#xD;
      or open-label ibuprofen every 6 to 8 hours in the 24 hours after receipt of a dose of IIV.&#xD;
      Children will be followed for the occurrence of fever, fussiness, changes in appetite and&#xD;
      sleep patterns, and use of medical services on the day of and for two days following&#xD;
      vaccination. Antibody to influenza antigens contained in the respective 2014-2015 and&#xD;
      2015-2016 vaccines as measured by hemagglutination inhibition (HAI) antibody will be assessed&#xD;
      at baseline and four weeks following vaccination. The proportions of children experiencing&#xD;
      fever, having solicited side effects, using medical services, demonstrating a serologic&#xD;
      response corresponding to seroprotection and seroconversion to each of the IIV antigens will&#xD;
      be determined for groups of children in each of the three treatment arms. Likewise geometric&#xD;
      mean HAI titers (GMTs) and corresponding 95% confidence intervals for each IIV antigen will&#xD;
      be calculated for the three treatment arms. The investigators hope to learn whether or not&#xD;
      prophylactic antipyretics affect the immune response and fever rates following IIV.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>N/A</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Seroconversion</measure>
    <time_frame>One month following the last dose of IIV</time_frame>
    <description>Seroconversion (an HAI titer ≥ 1:40 four weeks post- vaccination if the baseline titer is &lt; 1:10 or a four-fold rise in HAI titer if the baseline titer is ≥ 1:10) for each IIV antigen</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seroprotection</measure>
    <time_frame>One month following the last dose of IIV</time_frame>
    <description>Seroprotection (the proportion of subjects with an HAI titer &gt;1:40) to each IIV antigen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean HAI titer</measure>
    <time_frame>One month following the last dose of IIV</time_frame>
    <description>Geometric mean HAI titer (GMT) and 95% confidence interval for each IIV antigen</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fever</measure>
    <time_frame>Days 0, 1, and 2 following IIV</time_frame>
    <description>Proportions of children with fever (≥ 38°C and ≥ 39°C) on days 0, 1, and 2 following IIV</description>
  </other_outcome>
  <other_outcome>
    <measure>Systemic symptoms following IIV</measure>
    <time_frame>Days 0, 1, and 2 following IIV</time_frame>
    <description>Proportions of children with fussiness, appetite change, or altered sleep on days 0, 1, and 2 following IIV</description>
  </other_outcome>
  <other_outcome>
    <measure>Receipt of medical attention</measure>
    <time_frame>Days 0, 1, and 2 following IIV</time_frame>
    <description>Proportions of children receiving medical attention on days 0, 1, and 2 following IIV</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Fever</condition>
  <arm_group>
    <arm_group_label>Acetaminophen Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Acetaminophen Suspension 160mg / 5mL Oral dose immediately following IIV and every 4 to 6 hours up to 24 hours (Maximum 5 oral doses)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Suspension Oral dose immediately following IIV and every 4 to 6 hours up to 24 hours (Maximum 5 oral doses)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ibuprofen Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ibuprofen Suspension 100mg / 5mL Oral dose immediately following IIV and every 6 to 8 hours up to 24 hours (Maximum 4 oral doses)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Acetaminophen Arm</intervention_name>
    <description>Blinded Therapy</description>
    <arm_group_label>Acetaminophen Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Arm</intervention_name>
    <description>Blinded Therapy</description>
    <arm_group_label>Placebo Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ibuprofen Arm</intervention_name>
    <description>Open Label Therapy</description>
    <arm_group_label>Ibuprofen Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The child must be 6 through 47 months of age.&#xD;
&#xD;
          2. The child must weigh 5.4 kilograms.&#xD;
&#xD;
          3. The child must be receiving IIV this season.&#xD;
&#xD;
          4. If the child is two years of age or older and needs two doses of influenza vaccine&#xD;
             this season the parent/guardian intends for the child to receive IIV for the second&#xD;
             dose.&#xD;
&#xD;
          5. The parent/guardian must be willing and capable of providing written informed consent&#xD;
             for the child.&#xD;
&#xD;
          6. The parent/guardian must be available for follow-up and must at minimum have telephone&#xD;
             access.&#xD;
&#xD;
          7. The parent/guardian must agree to sign a medical release for the child so that study&#xD;
             personnel may obtain medical information about the child's health (if needed).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of receipt of current year's licensed influenza vaccine.&#xD;
&#xD;
          2. Planned receipt of the live attenuated nasally administered influenza vaccine this&#xD;
             year&#xD;
&#xD;
          3. History of a severe allergic reaction (e.g. anaphylaxis) to any component of influenza&#xD;
             vaccine, including egg protein, formaldehyde, octylphenol ethoxylate, gelatin, or&#xD;
             thimerosal if using thimerosal containing vaccine.&#xD;
&#xD;
          4. History of a severe allergic reaction (e.g. anaphylaxis) following a prior dose of&#xD;
             influenza vaccine.&#xD;
&#xD;
          5. History of an allergic reaction following acetaminophen or ingredients in the&#xD;
             acetaminophen product.&#xD;
&#xD;
          6. History of an allergic reaction following ibuprofen or ingredients in the ibuprofen&#xD;
             product.&#xD;
&#xD;
          7. History of an allergic reaction following aspirin or other pain reliever or fever&#xD;
             reducer.&#xD;
&#xD;
          8. History of liver disease.&#xD;
&#xD;
          9. Currently taking the blood thinning drug warfarin (Coumadin) or other blood thinners.&#xD;
&#xD;
         10. History of recent or planned heart surgery within the past 3 months or next 3 months.&#xD;
&#xD;
         11. History of stomach ulcer or bleeding problem.&#xD;
&#xD;
         12. Currently already routinely taking prescription or nonprescription non-steroidal&#xD;
             anti-inflammatory drugs or NSAIDs (aspirin, ibuprofen, naproxen, or others)&#xD;
&#xD;
         13. Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28&#xD;
             days (for live vaccines) prior to vaccination in this study or expects to receive a&#xD;
             licensed vaccine during the 28 days following the last influenza vaccination in this&#xD;
             study. Concomitant vaccinations are not allowed.&#xD;
&#xD;
         14. Routine immunizations are delayed or will be delayed by not being able to receive a&#xD;
             concomitantly administered vaccine or a needed vaccine in the 28 days following the&#xD;
             last influenza vaccination in this study.&#xD;
&#xD;
         15. Received an experimental/investigational agent (vaccine, drug, biologic, device, blood&#xD;
             product, or medication) within 28 days prior to vaccination in this study, or expects&#xD;
             to receive an experimental/investigational agent within the follow-up time period (28&#xD;
             days after the last vaccination in this study).&#xD;
&#xD;
         16. A moderate to severe acute illness and/or a reported temperature greater than or equal&#xD;
             to 100.0°F (37.8°C) within 72 hours prior to first dose of IIV or an axillary&#xD;
             temperature greater than or equal to 100.0°F (37.8°C) at the time of enrollment. (This&#xD;
             may result in a temporary delay of vaccination. For those needing a second dose of&#xD;
             IIV, a moderate to severe acute illness and/or a reported temperature greater than or&#xD;
             equal to 100.0°F (37.8°C) within 72 hours prior to second dose of IIV may result in a&#xD;
             temporary delay of vaccination).&#xD;
&#xD;
         17. Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 72 hours&#xD;
             prior to the first dose of IIV (This may result in a temporary delay of vaccination)&#xD;
             or is already planning to administer a prophylactic antipyretic medication on the day&#xD;
             of and the day following any dose of IIV (this exclusion does not apply if the&#xD;
             caretaker indicates he/she might administer antipyretics after vaccination to reduce a&#xD;
             fever).&#xD;
&#xD;
         18. Immunosuppression as a result of an underlying illness or treatment, or use of&#xD;
             anti-cancer chemotherapy or radiation therapy within the preceding 36 months.&#xD;
&#xD;
         19. Long term (at least 14 days of prednisone 2 mg/kg/day or equivalent other&#xD;
             glucocorticoid), any parenteral steroids, high-dose inhaled steroids (&gt;800 mcg/day of&#xD;
             beclomethasone dipropionate or equivalent) within the preceding 6 months (topical and&#xD;
             nasal steroids are allowed).&#xD;
&#xD;
         20. History of Guillain-Barré syndrome within 6 weeks of a prior dose of influenza&#xD;
             vaccine.&#xD;
&#xD;
         21. Has any condition that would, in the opinion of the site investigator, place the&#xD;
             participant at an unacceptable risk of injury or render the participant unable to meet&#xD;
             the requirements of the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>47 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emmanuel B Walter, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Unviersity School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karen Broder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centers for Diseaes Control and Prevention</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Health System</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>February 5, 2018</last_update_submitted>
  <last_update_submitted_qc>February 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fever</keyword>
  <keyword>Antipyretics</keyword>
  <keyword>Acetaminophen</keyword>
  <keyword>Ibuprofen</keyword>
  <keyword>Influenza vaccine</keyword>
  <keyword>Influenza</keyword>
  <keyword>Body temperature changes</keyword>
  <keyword>Signs and symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Ibuprofen</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02212990
org study id: Pro00056213
secondary id: 200-2012-53663
nct id: NCT02212990
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to conduct a double-blind, placebo-controlled study to assess the effect of
      prophylactic antipyretics on the immune responses and rates of fever after inactivated
      influenza vaccine (IIV) in children 6 through 47 months of age.

      In this study, 160 healthy children, 6 through 47 months of age, including some children at
      risk of febrile seizure, will be randomized to one of three different treatment arms.
      Children will receive either blinded therapy with prophylactic acetaminophen or placebo
      immediately following and every 4 to 6 hours in the 24 hours after receipt of a dose of IIV
      or open-label ibuprofen every 6 to 8 hours in the 24 hours after receipt of a dose of IIV.
      Children will be followed for the occurrence of fever, fussiness, changes in appetite and
      sleep patterns, and use of medical services on the day of and for two days following
      vaccination. Antibody to influenza antigens contained in the respective 2014-2015 and
      2015-2016 vaccines as measured by hemagglutination inhibition (HAI) antibody will be assessed
      at baseline and four weeks following vaccination. The proportions of children experiencing
      fever, having solicited side effects, using medical services, demonstrating a serologic
      response corresponding to seroprotection and seroconversion to each of the IIV antigens will
      be determined for groups of children in each of the three treatment arms. Likewise geometric
      mean HAI titers (GMTs) and corresponding 95% confidence intervals for each IIV antigen will
      be calculated for the three treatment arms. The investigators hope to learn whether or not
      prophylactic antipyretics affect the immune response and fever rates following IIV.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Seroconversion
time frame: One month following the last dose of IIV
description: Seroconversion (an HAI titer ≥ 1:40 four weeks post- vaccination if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer is ≥ 1:10) for each IIV antigen
measure: Seroprotection
time frame: One month following the last dose of IIV
description: Seroprotection (the proportion of subjects with an HAI titer >1:40) to each IIV antigen
measure: Geometric mean HAI titer
time frame: One month following the last dose of IIV
description: Geometric mean HAI titer (GMT) and 95% confidence interval for each IIV antigen
measure: Fever
time frame: Days 0, 1, and 2 following IIV
description: Proportions of children with fever (≥ 38°C and ≥ 39°C) on days 0, 1, and 2 following IIV
measure: Systemic symptoms following IIV
time frame: Days 0, 1, and 2 following IIV
description: Proportions of children with fussiness, appetite change, or altered sleep on days 0, 1, and 2 following IIV
measure: Receipt of medical attention
time frame: Days 0, 1, and 2 following IIV
description: Proportions of children receiving medical attention on days 0, 1, and 2 following IIV
arm group label: Acetaminophen Arm
arm group type: Active Comparator
description: Acetaminophen Suspension 160mg / 5mL Oral dose immediately following IIV and every 4 to 6 hours up to 24 hours (Maximum 5 oral doses)
arm group label: Placebo Arm
arm group type: Placebo Comparator
description: Placebo Suspension Oral dose immediately following IIV and every 4 to 6 hours up to 24 hours (Maximum 5 oral doses)
arm group label: Ibuprofen Arm
arm group type: Active Comparator
description: Ibuprofen Suspension 100mg / 5mL Oral dose immediately following IIV and every 6 to 8 hours up to 24 hours (Maximum 4 oral doses)
intervention type: Other
intervention name: Acetaminophen Arm
description: Blinded Therapy
arm group label: Acetaminophen Arm
intervention type: Other
intervention name: Placebo Arm
description: Blinded Therapy
arm group label: Placebo Arm
intervention type: Other
intervention name: Ibuprofen Arm
description: Open Label Therapy
arm group label: Ibuprofen Arm
criteria: 
gender: All
minimum age: 6 Months
maximum age: 47 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Emmanuel B Walter, MD, MPH
role: Principal Investigator
affiliation: Duke Unviersity School of Medicine
last name: Karen Broder, MD
role: Principal Investigator
affiliation: Centers for Diseaes Control and Prevention
facility: 
country: United States
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Fever
mesh term: Acetaminophen
mesh term: Ibuprofen