Fever After VaccinationPhase 4NCT03165981
Fever After Simultaneous Versus Sequential Vaccination in Young Children
A Phase 4 study testing PCV13, DTaP and IIV in people with Fever After Vaccination and Fever, run by Duke University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 16 monthsHealthy volunteers can take part
- Conditions the study is for
- Fever After Vaccination, Fever, Febrile Seizure
- What is being tested?
- PCV13, DTaP and IIV
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 221 participants
- Where
- 3 sitesUnited States
- Study dates
- 25 Aug 2017to 15 Jan 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 16 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Centers for Disease Control and Prevention
Atlanta, Georgia, 30333
Duke University
Durham, North Carolina, 27705
Kaiser Permanente Northern California
Oakland, California, 94612
About this study
Official title: A Prospective, Randomized, Open-label Clinical Trial to Assess Fever Following Simultaneous Versus Sequential Administration of PCV13, DTaP Vaccine and IIV in Young Children
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.
- Conditions
- Fever After Vaccination, Fever, Febrile Seizure
- Being tested
- PCV13, DTaP, IIV
- Keywords
- Influenza vaccine, fever following vaccination, PCV13 vaccine, DTaP vaccine, pneumococcal vaccine
- Medical subject headings
- Fever, Seizures, Febrile, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCV13Biological
Also called 13-valent Conjugate Pneumococcal Vaccine
ACIP Recommended vaccine
DTaPBiological
Also called Diphtheria, Tetanus, and Acellular Pertussis Vaccine
ACIP Recommended vaccine
IIVBiological
Also called Quadrivalent Inactivated Influenza Vaccine, IIV4, Flu Vaccine
ACIP Recommended vaccine
| Study group | Role | What they receive |
|---|---|---|
| Simultaneous vaccination arm | Other | 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. Receives: Biological: PCV13; Biological: DTaP; Biological: IIV |
| Sequential vaccination arm | Other | 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. Receives: Biological: PCV13; Biological: DTaP; Biological: IIV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 days post administration
Secondary outcomes (11)
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
Measured: 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
Measured: 2 days post administration
Number of Participants With Grade 2 and/or 3 Fever 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)
Measured: 2 days post administration
Number of Participants With Grade 2 and/or 3 Fever 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 days post administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2017
- Study start25 Aug 2017
- Primary completion15 Jan 2018
- Study completion15 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fever After VaccinationStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, Kaiser Permanente
- Responsible party
- Sponsor
- Investigators
- Emmanuel B Walter, MD, MPH, Principal investigator, Duke UniversityKaren Broder, MD, Principal investigator, Centers for Disease Control and PreventionNicola Klein, MD, PhD, Principal investigator, Kaiser Permanente
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03165981
- Sponsor's protocol ID
- Pro00082484
- Other IDs
- 200 2012 53663 0009
- Status last verified
- Oct 2024
- First submitted
- 23 May 2017
- Last updated
- 18 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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):e20191909. doi: 10.1542/peds.2019-1909. Epub 2020 Feb 6.
PubMed 32029684
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open-label Clinical Trial to Assess Fever Following Simultaneous Versus Sequential Administration of PCV13, DTaP Vaccine and IIV in Young Children
- ClinicalTrials.gov ID
- NCT03165981
- Acronym / sponsor ID
- Pro00082484
- Conditions
- Fever After Vaccination, Fever, Febrile Seizure
- Keywords
- Influenza vaccine, fever following vaccination, PCV13 vaccine, DTaP vaccine, pneumococcal vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, Kaiser Permanente
- Study start
- 25 Aug 2017 (actual)
- Primary completion
- 15 Jan 2018 (actual)
- Study completion
- 15 Jan 2018 (actual)
- First posted
- 24 May 2017 (actual)
- Results
- Posted 8 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Simultaneous vaccination arm | Other | Biological: PCV13, Biological: DTaP, Biological: IIVIn 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. |
| Sequential vaccination arm | Other | Biological: PCV13, Biological: DTaP, Biological: IIVIn 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. |
Who may qualify
- Ages
- 12 to 16 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PCV13Also: 13-valent Conjugate Pneumococcal VaccineACIP Recommended vaccine | Biological | Sequential vaccination arm, Simultaneous vaccination arm |
| DTaPAlso: Diphtheria, Tetanus, and Acellular Pertussis VaccineACIP Recommended vaccine | Biological | Sequential vaccination arm, Simultaneous vaccination arm |
| IIVAlso: Quadrivalent Inactivated Influenza Vaccine, IIV4, Flu VaccineACIP Recommended vaccine | Biological | Sequential vaccination arm, Simultaneous vaccination arm |
Primary outcome
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.
11 secondary outcomes
Number of Participants With Fever Visit 1
Time frame: 2 days post administration
Number of Participants With Fever Visit 2
Time frame: 2 days post administration
Number of Participants With Grade 2 and/or 3 Fever Following Visit 1
Time frame: 2 days post administration
Number of Participants With Grade 2 and/or 3 Fever Following Visit 2
Time frame: 2 days post administration
Number of Participants With Grade 2 and/or 3 Following Visit 1 and Visit 2
Time frame: 2 days post administration
Duration of Fever - Visit 1
Time frame: 8 days post administration
Duration of Fever - Visit 2
Time frame: 8 days post administration
Duration of Fever - Visit 1 and 2 Combined
Time frame: 8 days post administration
Number of Participants With Medical Care Utilization - Visit 1
Time frame: 2 days post administration
Number of Participants With Medical Care Utilization - Visit 2
Time frame: 2 days post administration
Number of Participants With Medical Care Utilization - Visit 1 and 2 Combined
Time frame: 2 days post administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32029684Walter 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):e20191909. doi: 10.1542/peds.2019-1909. Epub 2020 Feb 6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanuel B Walter, MD, MPH principal investigator
Duke University
Karen Broder, MD principal investigator
Centers for Disease Control and Prevention
Nicola Klein, MD, PhD principal investigator
Kaiser Permanente
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PCV13, DTaP and IIV in people with Fever After Vaccination and Fever, run by Duke University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Fever Following Vaccination (time frame: 2 days post administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03165981, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.