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Fever After Simultaneous Versus Sequential Vaccination in Young Children

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ClinicalTrials.gov Identifier: NCT03165981
Recruitment Status : Completed
First Posted : May 24, 2017
Results First Posted : February 8, 2019
Last Update Posted : February 8, 2019
Sponsor:
Collaborators:
Centers for Disease Control and Prevention
Kaiser Permanente
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE May 23, 2017
First Posted Date  ICMJE May 24, 2017
Results First Submitted Date  ICMJE December 31, 2018
Results First Posted Date  ICMJE February 8, 2019
Last Update Posted Date February 8, 2019
Actual Study Start Date  ICMJE August 25, 2017
Actual Primary Completion Date January 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 5, 2019)		 Number of Participants With Fever Following Vaccination [ Time Frame: 2 days post administration ]
Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and/or Visit 2.
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2017)		 Proportions of Children with Fever following Vaccination [ Time Frame: 2 days post administration ]
Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and/or Visit 2.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 5, 2019)
  • Number of Participants With Fever Visit 1 [ Time Frame: 2 days post administration ]
    Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1
  • Number of Participants With Fever Visit 2 [ Time Frame: 2 days post administration ]
    Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2
  • Number of Participants With Grade 2 and/or 3 Following Visit 1 [ Time Frame: 2 days post administration ]
    Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1. (Moderate/severe fever: ≥ 38.6°C or ≥ 101.4°F)
  • Number of Participants With Grade 2 and/or 3 Following Visit 2 [ Time Frame: 2 days post administration ]
    Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 2.
  • Number of Participants With Grade 2 and/or 3 Following Visit 1 and Visit 2 [ Time Frame: 2 days post administration ]
    Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Duration of Fever - Visit 1 [ Time Frame: 8 days post administration ]
    Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following Visit 1. Note: fever starting on day 1 or 2 could continue through day 8.
  • Duration of Fever - Visit 2 [ Time Frame: 8 days post administration ]
    Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following Visit 2. Note: fever starting on day 1 or 2 could continue through day 8.
  • Duration of Fever - Visit 1 and 2 Combined [ Time Frame: 8 days post administration ]
    Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following and Visit 1 and Visit 2 combined. Note: fever starting on day 1 or 2 could continue through day 8.
  • Number of Participants With Medical Care Utilization - Visit 1 [ Time Frame: 2 days post administration ]
    Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 1.
  • Number of Participants With Medical Care Utilization - Visit 2 [ Time Frame: 2 days post administration ]
    Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 2.
  • Number of Participants With Medical Care Utilization - Visit 1 and 2 Combined [ Time Frame: 2 days post administration ]
    Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
  • Fever Severity Visit 1 [ Time Frame: 2 days post administration ]
    Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1
  • Fever Severity Visit 2 [ Time Frame: 2 days post administration ]
    Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2
  • Degrees of Fever - Visit 1 (38.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 38.0°C (≥ 100.4°F) on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 (38.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 38.0°C (≥ 100.4°F) on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined (38.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 38.0°C (≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 (38.5°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 38.5°C (≥ 101.3°F) on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 (38.5°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 38.5°C (≥ 101.3°F) on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined (38.5°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 38.5°C (≥ 101.3°F) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 (39.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 39.0°C (≥ 102.2°F) on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 (39.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 39.0°C (≥ 102.2°F) on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined (39.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 39.0°C (≥ 102.2°F) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 (39.5°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 39.5°C (≥ 103.1°F) on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 (39.5°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 39.5°C (≥ 103.1°F) on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined (39.5°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 39.5°C (≥ 103.1°F) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 (40.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 40.0°C (≥ 104.0°F) on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 (40.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 40.0°C (≥ 104.0°F) on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined (40.0°C) [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at temperature ≥ 40.0°C (≥ 104.0°F) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 Grade 1 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 1 severity on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 Grade 1 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 1 severity on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined Grade 1 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 1 severity on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 Grade 2 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 2 severity on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 Grade 2 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 2 severity on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined Grade 2 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 2 severity on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Degrees of Fever - Visit 1 Grade 3 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 3 severity on day 1 and/or day 2 following Visit 1.
  • Degrees of Fever - Visit 2 Grade 3 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 3 severity on day 1 and/or day 2 following Visit 2.
  • Degrees of Fever - Visit 1 and 2 Combined Grade 3 [ Time Frame: 2 days post administration ]
    Proportions of children with fever defined at Grade 3 severity on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Peak Temperature - Visit 1 [ Time Frame: 2 days post administration ]
    Average peak temperature of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1.
  • Peak Temperature - Visit 2 [ Time Frame: 2 days post administration ]
    Average peak temperature of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2.
  • Peak Temperature - Visit 1 and 2 Combined [ Time Frame: 2 days post administration ]
    Average peak temperature of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Fever Degree-days - Visit 1 [ Time Frame: 2 days post administration ]
    Total number of fever degree-days (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 per subject following Visit 1.
  • Fever Degree-days - Visit 2 [ Time Frame: 2 days post administration ]
    Total number of fever degree-days (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 per subject following Visit 2.
  • Fever Degree-days - Visit 1 and 2 Combined [ Time Frame: 2 days post administration ]
    Total number of fever degree-days (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 per subject following Visit 1 and Visit 2 combined.
  • Length of Fever - Visit 1 [ Time Frame: 8 days post administration ]
    Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following and Visit 1. Note: fever starting on day 1 or 2 could continue through day 8.
  • Length of Fever - Visit 2 [ Time Frame: 8 days post administration ]
    Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following and Visit 2. Note: fever starting on day 1 or 2 could continue through day 8.
  • Length of Fever - Visit 1 and 2 Combined [ Time Frame: 8 days post administration ]
    Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following and Visit 1 and Visit 2 combined. Note: fever starting on day 1 or 2 could continue through day 8.
  • Medical Care Utilization - Visit 1 [ Time Frame: 2 days post administration ]
    Proportion of children with medical care utilization (medical office, urgent care, emergency department, or hospital admission) for fever on day 1 and/or day 2 following Visit 1.
  • Medical Care Utilization - Visit 2 [ Time Frame: 2 days post administration ]
    Proportion of children with medical care utilization (medical office, urgent care, emergency department, or hospital admission) for fever on day 1 and/or day 2 following Visit 2.
  • Medical Care Utilization - Visit 1 and 2 Combined [ Time Frame: 2 days post administration ]
    Proportion of children with medical care utilization (medical office, urgent care, emergency department, or hospital admission) for fever on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
  • Antipyretic Use - Visit 1 [ Time Frame: 2 days post administration ]
    Proportion of children with antipyretic use for fever on day 1 and/or day 2 following Visit 1.
  • Antipyretic Use - Visit 2 [ Time Frame: 2 days post administration ]
    Proportion of children with antipyretic use for fever on day 1 and/or day 2 following Visit 2.
  • Antipyretic Use - Visit 1 and 2 Combined [ Time Frame: 2 days post administration ]
    Proportion of children with antipyretic use for fever on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fever After Simultaneous Versus Sequential Vaccination in Young Children
Official Title  ICMJE A Prospective, Randomized, Open-label Clinical Trial to Assess Fever Following Simultaneous Versus Sequential Administration of PCV13, DTaP Vaccine and IIV in Young Children
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Fever After Vaccination
  • Fever
  • Febrile Seizure
Intervention  ICMJE
  • Biological: PCV13
    ACIP Recommended vaccine
    Other Name: 13-valent Conjugate Pneumococcal Vaccine
  • Biological: DTaP
    ACIP Recommended vaccine
    Other Name: Diphtheria, Tetanus, and Acellular Pertussis Vaccine
  • Biological: IIV
    ACIP Recommended vaccine
    Other Names:
    • Quadrivalent Inactivated Influenza Vaccine
    • IIV4
    • Flu Vaccine
Study Arms  ICMJE
  • Simultaneous vaccination arm
    In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2.
    Interventions:
    • Biological: PCV13
    • Biological: DTaP
    • Biological: IIV
  • Sequential vaccination arm
    In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2.
    Interventions:
    • Biological: PCV13
    • Biological: DTaP
    • Biological: IIV
Publications * Walter EB, Klein NP, Wodi AP, Rountree W, Todd CA, Wiesner A, Duffy J, Marquez PL, Broder KR. Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations. Pediatrics. 2020 Mar;145(3). pii: e20191909. doi: 10.1542/peds.2019-1909. Epub 2020 Feb 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 21, 2018)		 221
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2017)		 280
Actual Study Completion Date  ICMJE January 15, 2018
Actual Primary Completion Date January 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 16 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03165981
Other Study ID Numbers  ICMJE Pro00082484
200 2012 53663 0009 ( Other Grant/Funding Number: CDC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE
  • Centers for Disease Control and Prevention
  • Kaiser Permanente
Investigators  ICMJE
Principal Investigator: Emmanuel B Walter, MD, MPH Duke University
Principal Investigator: Karen Broder, MD Centers for Disease Control and Prevention
Principal Investigator: Nicola Klein, MD, PhD Kaiser Permanente
PRS Account Duke University
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP