Fever After Simultaneous Versus Sequential Vaccination in Young Children
Condition: Fever After Vaccination; Fever; Febrile Seizure
MeSH terms: Seizures; Seizures, Febrile; Fever; Hyperthermia
Intervention: PCV13; DTaP; IIV
Intervention description: ACIP Recommended vaccine; ACIP Recommended vaccine; ACIP Recommended vaccine
Intervention MeSH terms: Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 221.0
Sex: All
Minimum age: 12 Months
Maximum age: 16 Months
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Influenza vaccine; fever following vaccination; PCV13 vaccine; DTaP vaccine; pneumococcal vaccine

Summary:

      A prospective, randomized open-label clinical trial that will be conducted during the
      2017-2018 influenza season. During the 2017-2018 season, approximately 280 children will be
      enrolled at Duke University Medical Center and Kaiser Permanente Northern California.
      Eligible children will be randomized to receive simultaneous or sequentially administered US
      licensed PCV13, US-licensed DTaP vaccine, and US-licensed inactivated influenza vaccine
      (IIV). Children in the simultaneous group will receive PCV13, DTaP, and IIV vaccines at Visit
      1, and then return for a health education visit without vaccination about 2 weeks later
      (Visit 2). Children in the sequential group will receive both PCV13 and DTaP without IIV at
      Visit 1, and then will receive IIV and health education about 2 weeks later (Visit 2).
      Parents will record the occurrence of fever, solicited adverse events, medical care
      utilization, and receipt of antipyretics over 8 days following Visit 1 and Visit 2. In
      addition, febrile seizures and serious adverse events will be recorded for the entire study
      period (from enrollment through 8 days following the Visit 2) as determined through parental
      report and chart review. Parental perceptions about their child's vaccine schedule will be
      assessed on the 8th day following Visit 2.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 12 through 16 months of age (i.e. from the 1-year birthday until the day before 17
             months of age) at the time of vaccination

          2. Stable health as determined by investigator's clinical examination and assessment of
             child's medical history

          3. Has received all immunizations recommended by Advisory Committee for Immunization
             Practices (ACIP) during the first year of life with the exception of rotavirus and
             influenza vaccines.

          4. The parent(s)/ legally authorized representative(s) LAR(s) intend for the child to
             receive DTaP and PCV13 in addition to this season's IIV

          5. The parent(s)/LAR(s) must be willing and capable of providing permission for their
             child to participate through the written informed consent process

          6. The parent(s)/LAR(s) must be able to comply with the requirements of the protocol
             (e.g., completion of the memory aid (either electronic or paper diary), return for
             follow-up visits, respects intervals between the visits and have telephone access.

          7. The parent(s)/LAR(s) must be English speaking

          8. The parent(s)/LAR(s) must agree to sign a medical release for the child so that study
             personnel may obtain medical information about the child's health (if needed)

        Exclusion Criteria:

          1. History of any seizure (including febrile seizure) in the child or a febrile seizure
             in a first degree relative

          2. Has already completed influenza vaccination during the current season per ACIP
             recommendations

          3. Receipt of more than 3 previous doses of DTaP

          4. Received the 3rd dose of DTaP within 6 months of Visit 1

          5. Receipt of more than 3 previous doses of PCV13

          6. Received the 3rd dose of PCV13 within 8 weeks of Visit 1

          7. History of a severe allergic reaction (e.g. anaphylaxis) to a previous dose of any
             influenza, diphtheria toxoid-, tetanus toxoid-, or pertussis-containing vaccine, or
             pneumococcal vaccine.

          8. History of a severe allergic reaction (e.g., anaphylaxis) to any component (including
             egg protein) of any of the three vaccines used in this study; or a latex allergy.

          9. History of Guillain-Barré syndrome within 6 weeks following a prior dose of influenza,
             DTaP, or tetanus toxoid containing vaccine

         10. History of a progressive neurologic disorder

         11. History of encephalopathy within 7 days of a previous pertussis-containing vaccine

         12. History of collapse within 3 days after a prior dose of DTaP

         13. Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28
             days (for live vaccines) prior to Visit 1

         14. Received an experimental/investigational agent (vaccine, drug, biologic, device, blood
             product, or medication) within 28 days prior to Visit 1, or expects to receive an
             experimental/investigational agent during the study period (up to 8 days after visit
             2)

         15. A moderate to severe acute illness within 72 hours of Visit 1

         16. A reported temperature greater than or equal to 100.4°F (38.0°C) within 72 hours prior
             enrollment or a temperature (measured by temporal artery thermometer) greater than or
             equal to 100.4°F (38.0°C) at the time of enrollment

         17. Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 24 hours
             prior to enrollment

         18. Parent(s)/LAR is planning to administer a prophylactic antipyretic or medication on
             the day of, and/or within 7 days following Visit 1 or Visit 2

         19. Long term (at least 14 consecutive days) oral corticosteroids (prednisone 2 mg/kg/day
             or equivalent other glucocorticoid), any parenteral steroids, high-dose inhaled
             steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) or other
             immune-modifying drugs or immunosuppressants within the preceding 6 months prior to
             Visit 1

         20. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and or their provider's routine physical examination

         21. Has an active neoplastic disease, a history of any hematologic malignancy, current
             bleeding disorder, or taking anticoagulants.

         22. Unable to receive an intramuscular injection in the thigh

         23. Any condition deemed by the investigator to place the child at increased risk as a
             result of their participation in the study

         24. Any child or grandchild of a study investigator or study team member