Fever After Simultaneous Versus Sequential Vaccination in Young Children

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective, Randomized, Open-label Clinical Trial to Assess Fever Following Simultaneous Versus Sequential Administration of PCV13, DTaP Vaccine and IIV in Young Children

Conditions
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Fever After Vaccination, Fever, Febrile Seizure

Intervention / Treatment
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* Biological: PCV13
* Biological: DTaP
* Biological: IIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Stable health as determined by investigator's clinical examination and assessment of child's medical history 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. 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 The parent(s)/LAR(s) must be willing and capable of providing permission for their child to participate through the written informed consent process 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. The parent(s)/LAR(s) must be English speaking 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: History of any seizure (including febrile seizure) in the child or a febrile seizure in a first degree relative Has already completed influenza vaccination during the current season per ACIP recommendations Receipt of more than 3 previous doses of DTaP Received the 3rd dose of DTaP within 6 months of Visit 1 Receipt of more than 3 previous doses of PCV13 Received the 3rd dose of PCV13 within 8 weeks of Visit 1 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. 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. History of Guillain-Barré syndrome within 6 weeks following a prior dose of influenza, DTaP, or tetanus toxoid containing vaccine History of a progressive neurologic disorder History of encephalopathy within 7 days of a previous pertussis-containing vaccine History of collapse within 3 days after a prior dose of DTaP Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Visit 1 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) A moderate to severe acute illness within 72 hours of Visit 1 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 Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 24 hours prior to enrollment 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 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 Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and or their provider's routine physical examination Has an active neoplastic disease, a history of any hematologic malignancy, current bleeding disorder, or taking anticoagulants. Unable to receive an intramuscular injection in the thigh Any condition deemed by the investigator to place the child at increased risk as a result of their participation in the study Any child or grandchild of a study investigator or study team member

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 16 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Simultaneous vaccination arm<br>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. | Biological: PCV13<br>* ACIP Recommended vaccine<br>* Other names: 13-valent Conjugate Pneumococcal Vaccine;Biological: DTaP<br>* ACIP Recommended vaccine<br>* Other names: Diphtheria, Tetanus, and Acellular Pertussis Vaccine;Biological: IIV<br>* ACIP Recommended vaccine<br>* Other names: Flu Vaccine;|
| Other: Sequential vaccination arm<br>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. | Biological: PCV13<br>* ACIP Recommended vaccine<br>* Other names: 13-valent Conjugate Pneumococcal Vaccine;Biological: DTaP<br>* ACIP Recommended vaccine<br>* Other names: Diphtheria, Tetanus, and Acellular Pertussis Vaccine;Biological: IIV<br>* ACIP Recommended vaccine<br>* Other names: Flu Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Fever Following Vaccination | 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. | 2 days post administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Fever Visit 1 | Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 | 2 days post administration | 
| Number of Participants With Fever Visit 2 | Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2 | 2 days post administration | 
| Number of Participants With Grade 2 and/or 3 Following Visit 1 | 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) | 2 days post administration | 
| Number of Participants With Grade 2 and/or 3 Following Visit 2 | Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 2. | 2 days post administration | 
| Number of Participants With Grade 2 and/or 3 Following Visit 1 and Visit 2 | 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. | 2 days post administration | 
| Duration of Fever - Visit 1 | 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. | 8 days post administration | 
| Duration of Fever - Visit 2 | 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. | 8 days post administration | 
| Duration of Fever - Visit 1 and 2 Combined | 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. | 8 days post administration | 
| Number of Participants With Medical Care Utilization - Visit 1 | 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. | 2 days post administration | 
| Number of Participants With Medical Care Utilization - Visit 2 | 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. | 2 days post administration | 
| Number of Participants With Medical Care Utilization - Visit 1 and 2 Combined | 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. | 2 days post administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine, fever following vaccination, PCV13 vaccine, DTaP vaccine, pneumococcal vaccine