Fever After VaccinationPhase 4NCT06038617
Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children
A Phase 4 study testing mRNA COVID-19 Vaccine and Routine Childhood Vaccinations in people with Fever After Vaccination and Fever, run by Duke University at 5 sites in United States.
Trial summary
This is a prospective, randomized, open-label clinical trial to evaluate the safety of COVID-19 vaccination and other routine childhood vaccines given simultaneously at Visit 1, as compared to sequential vaccination of COVID-19 vaccine and other vaccines at separate visits (Visits 1 and 2). Read more about this study
- Who is it for?
- Ages 6 months to 4 yearsHealthy volunteers can take part
- Conditions the study is for
- Fever After Vaccination, Fever, Seizures Fever
- What is being tested?
- mRNA COVID-19 Vaccine and Routine Childhood Vaccinations
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 347 participants
- Where
- 5 sitesUnited States
- Study dates
- 30 Oct 2023to 25 Jul 2025
- 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 6 months to 4 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Child 6 months through <5 years of age at time of enrollment.
- Child is due to receive mRNA COVID-19 vaccine and at least one other routinely recommended non-live vaccine per CDC or ACIP recommendations.
- Parental/LAR intention of child receiving mRNA COVID-19 vaccine and at least one recommended non-live vaccine.
- The parent/LAR must be willing and capable of providing permission for their child to participate through the written informed consent process.
- The parent/LAR must be available for follow-up and must at minimum have telephone access.
- The parent/LAR 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).
- The parent/LAR must be willing to delay COVID-19 vaccination for their child for up to 3 weeks.
- The parent/LAR must be able to read English or Spanish.
Who cannot join
- History of any seizure (including febrile seizure) or first degree relative (biologic parent or biologic sibling including half-sibling) with a history of febrile seizure.
- Contraindication to mRNA COVID-19 vaccine: A history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of the COVID-19 vaccine or a known diagnosed allergy to a component of COVID-19 vaccine.
- A history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of a vaccine administered on the day of study enrollment.
- For children receiving DTaP vaccine (alone or combination vaccine): Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures), not attributable to another identifiable cause, within 7 days of administration of previous dose of DTP or DTaP.
- Received any other non-live vaccines within 14 days prior to enrollment or any other live vaccines within 28 days prior to enrollment.
- Intention to receive non-COVID-19 non-live or live vaccines during the 4 weeks after Visit 1; vaccines may be administered after enrollment if deemed a personal or public health priority by the health care provider caring for this patient or the study team.
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- Received prior COVID-19 vaccine as part of a clinical trial.
- Received any experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to enrollment in this study or expects to receive an experimental/investigational agent during the study.
- A moderate to severe acute illness and/or a reported temperature ≥ 100.4°F (≥38.0°C) within 48 hours prior to enrollment or a temperature (measured by temporal artery thermometer) ≥100.4°F (≥38.0°C) at the time of enrollment. (This may result in a temporary delay of vaccination).
- Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 72 hours prior to enrollment (this may result in a temporary delay of vaccination) or planned receipt of a prophylactic antipyretic medication on the day of and/or days following vaccination prior to any measured increase in temperature in anticipation of a fever (this exclusion does not apply if the Parent/LAR indicates they might administer antipyretics or analgesics after vaccination to reduce a fever or pain).
- Immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy since birth.
- Long term (at least 14 days of prednisone 2 mg/kg/day or equivalent other glucocorticoid) use of any parenteral steroids or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the 6 months prior to enrollment (topical and nasal steroids are allowed).
- Has an active case of COVID-19 infection.
- History of multisystem inflammatory syndrome (MIS-C).
- History of myocarditis or pericarditis.
- Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
- Any child or grandchild of a study investigator or study team member.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Centers for Disease Control and Prevention
Atlanta, Georgia, 30333
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University
Durham, North Carolina, 27710
Columbia University
New York, New York, 10027
Kaiser Permanente Northern California
Oakland, California, 94612
About this study
Official title: A Prospective, Randomized, Open-label Clinical Trial to Assess the Safety of Simultaneous Vaccination With mRNA COVID-19 Vaccine and Other Vaccines in Young Children Aged 6 Months to <5 Years.
This is a prospective, randomized, open-label clinical trial to evaluate the safety of COVID-19 vaccination and other routine childhood vaccines given simultaneously at Visit 1, as compared to sequential vaccination of COVID-19 vaccine and other vaccines at separate visits (Visits 1 and 2).
Parent(s) or legal authorized representative(s) (LAR) will assess fever and other solicited systemic adverse events on the day of vaccination (Day 1) and the next 6 days (through Day 7) following Visit 1 and Visit 2 using either a web-based data collection system or a paper memory aid. Serious adverse events and adverse events of special interest will be captured during the entire study period. Parental/LAR perceptions about their child's vaccine schedule will be assessed on Day 7 following Visit 2.
Read the detailed description
Intent-to-Treat (ITT) Analysis Population: Defined as any participant who was enrolled and randomized into the study.
Modified Intent-to-Treat (mITT) Analysis Population: Defined as any participant who was enrolled, randomized into the study, and received at least one study vaccine at Visit 1.
- Conditions
- Fever After Vaccination, Fever, Seizures Fever
- Being tested
- mRNA COVID-19 Vaccine, Routine Childhood Vaccinations
- Keywords
- COVID vaccine, Fever following vaccination
- Medical subject headings
- Fever, Seizures, Febrile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mRNA COVID-19 VaccineBiological
Also called Pfizer COVID-19 Vaccine, Moderna COVID-19 Vaccine
ACIP Recommended Vaccine
Routine Childhood VaccinationsBiological
Also called Pneumococcal, DTaP, Haemophilus Influenzae Type B, MMR, Varicella, MMRV, Hepatitis A, Inactivated Poliovirus, Hepatitis B, Rotavirus, Influenza vaccines
ACIP Recommended Vaccines
| Study group | Role | What they receive |
|---|---|---|
| Simultaneous vaccination arm | Experimental | The simultaneous vaccination group will receive routine childhood vaccinations and mRNA COVID-19 vaccination at Visit 1, followed by a health education visit without vaccination at Visit 2. Receives: Biological: mRNA COVID-19 Vaccine; Biological: Routine Childhood Vaccinations |
| Sequential vaccination arm | Experimental | The sequential vaccination group will receive routine childhood vaccinations at Visit 1, followed by a health education visit with mRNA COVID-19 vaccination at Visit 2. Receives: Biological: mRNA COVID-19 Vaccine; Biological: Routine Childhood Vaccinations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Fever Following Vaccination
Number 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 (16)
Number of Participants With Fever Following Visit 1
Number 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 Visit 1
Number of Participants With Fever Following Visit 2
Number 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 Visit 2
Number of Participants With Grade 2 and/or 3 Fever Following Visit 1 and Visit 2 Combined
Number 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. (Moderate/severe fever: ≥ 38.4°C or ≥ 101.2°F)
Measured: 2 Days Post Administration
Number of Participants With Grade 2 and/or 3 Fever Following Visit 1
Number of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1. (Moderate/severe fever: ≥ 38.4°C or ≥ 101.2°F)
Measured: 2 Days Post Visit 1
Number of Participants With Grade 2 and/or 3 Fever Following Visit 2
Number of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 2. (Moderate/severe fever: ≥ 38.4°C or ≥ 101.2°F)
Measured: 2 Days Post Visit 2
Number of Participants With Medical Care Utilization for Fever - Visit 1 and Visit 2 Combined
Number of children with medical care utilization (medical advice (telephone, patient portal), urgent care visit, emergency department visit, and hospital admission) for fever on day 1 and /or day 2 following Visit 1 and Visit 2 combined.
Measured: 2 Days Post Administration
Number of Participants With Medical Care Utilization for Fever - Visit 1
Number of children with medical care utilization (medical advice (telephone, patient portal),urgent care visit, emergency department visit, and hospital admission) for fever on day 1 and/or day 2 following Visit 1.
Measured: 2 Days Post Visit 1
Number of Participants With Medical Care Utilization for Fever- Visit 2
Number of children with medical care utilization (medical advice (telephone, patient portal),urgent care visit, emergency department visit, and hospital admission) for fever on day 1 and/or day 2 following Visit 2.
Measured: 2 Days Post Visit 2
Number of Participants Who Received Antipyretics - Visit 1 and Visit 2 Combined
Number of children who received antipyretics on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
Measured: 2 Days Post Administration
Number of Participants Who Received Antipyretics - Visit 1
Number of children who received antipyretics on day 1 and/or day 2 following Visit 1.
Measured: 2 Days Post Visit 1
Number of Participants Who Received Antipyretics - Visit 2
Number of children who received antipyretics on day 1 and/or day 2 following Visit 2.
Measured: 2 Days Post Visit 2
Number of Participants With Defined Systemic Reactogenicity Events at Visit 1, Ages 6-23 Months Old
Tables summarizing each solicited local and systemic reactogenicity event by maximum classification (none, mild, moderate, and severe), as well as by moderate or severe
Measured: Up to 7 Days Post Visit 1
Number of Participants With Defined Systemic Reactogenicity Events at Visit 2, Ages 6-23 Months Old
Tables summarizing each solicited local and systemic reactogenicity event by maximum classification (none, mild, moderate, and severe), as well as by moderate or severe
Measured: Up to 7 Days Post Visit 2
Number of Participants With Defined Systemic Reactogenicity Events at Visit 1, Ages 2-5 Years Old
Tables summarizing each solicited local and systemic reactogenicity event by maximum classification (none, mild, moderate, and severe), as well as by moderate or severe
Measured: Up to 7 Days Post Visit 1
Number of Participants With Defined Systemic Reactogenicity Events at Visit 2, Ages 2-5 Years Old
Tables summarizing each solicited local and systemic reactogenicity event by maximum classification (none, mild, moderate, and severe), as well as by moderate or severe
Measured: Up to 7 Days Post Visit 2
The Number of Individuals With At Least One Serious Adverse Event
Measured: Up to 105 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 posted15 Sep 2023
- Study start30 Oct 2023
- Primary completion24 Apr 2025
- Study completion25 Jul 2025
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.
- 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
- 347 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Kaiser Permanente, Columbia University, Children's Hospital Medical Center, Cincinnati, Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Michael J Smith, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06038617
- Sponsor's protocol ID
- Pro00113014
- Status last verified
- May 2026
- First submitted
- 8 Sep 2023
- Last updated
- 13 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open-label Clinical Trial to Assess the Safety of Simultaneous Vaccination With mRNA COVID-19 Vaccine and Other Vaccines in Young Children Aged 6 Months to <5 Years.
- ClinicalTrials.gov ID
- NCT06038617
- Acronym / sponsor ID
- Pro00113014
- Conditions
- Fever After Vaccination, Fever, Seizures Fever
- Keywords
- COVID vaccine, Fever following vaccination
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 347 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Kaiser Permanente, Columbia University, Children's Hospital Medical Center, Cincinnati, Centers for Disease Control and Prevention
- Study start
- 30 Oct 2023 (actual)
- Primary completion
- 24 Apr 2025 (actual)
- Study completion
- 25 Jul 2025 (actual)
- First posted
- 15 Sep 2023 (actual)
- Results
- Posted 13 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, randomized, open-label clinical trial to evaluate the safety of COVID-19 vaccination and other routine childhood vaccines given simultaneously at Visit 1, as compared to sequential vaccination of COVID-19 vaccine and other vaccines at separate visits (Visits 1 and 2).
Parent(s) or legal authorized representative(s) (LAR) will assess fever and other solicited systemic adverse events on the day of vaccination (Day 1) and the next 6 days (through Day 7) following Visit 1 and Visit 2 using either a web-based data collection system or a paper memory aid. Serious adverse events and adverse events of special interest will be captured during the entire study period. Parental/LAR perceptions about their child's vaccine schedule will be assessed on Day 7 following Visit 2.
Detailed description
Intent-to-Treat (ITT) Analysis Population: Defined as any participant who was enrolled and randomized into the study.
Modified Intent-to-Treat (mITT) Analysis Population: Defined as any participant who was enrolled, randomized into the study, and received at least one study vaccine at Visit 1.
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 | Experimental | Biological: mRNA COVID-19 Vaccine, Biological: Routine Childhood VaccinationsThe simultaneous vaccination group will receive routine childhood vaccinations and mRNA COVID-19 vaccination at Visit 1, followed by a health education visit without vaccination at Visit 2. |
| Sequential vaccination arm | Experimental | Biological: mRNA COVID-19 Vaccine, Biological: Routine Childhood VaccinationsThe sequential vaccination group will receive routine childhood vaccinations at Visit 1, followed by a health education visit with mRNA COVID-19 vaccination at Visit 2. |
Who may qualify
- Ages
- 6 months to 4 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Child 6 months through <5 years of age at time of enrollment.
- Child is due to receive mRNA COVID-19 vaccine and at least one other routinely recommended non-live vaccine per CDC or ACIP recommendations.
- Parental/LAR intention of child receiving mRNA COVID-19 vaccine and at least one recommended non-live vaccine.
- The parent/LAR must be willing and capable of providing permission for their child to participate through the written informed consent process.
- The parent/LAR must be available for follow-up and must at minimum have telephone access.
Key exclusion criteria (17 listed)
- History of any seizure (including febrile seizure) or first degree relative (biologic parent or biologic sibling including half-sibling) with a history of febrile seizure.
- Contraindication to mRNA COVID-19 vaccine: A history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of the COVID-19 vaccine or a known diagnosed allergy to a component of COVID-19 vaccine.
- A history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of a vaccine administered on the day of study enrollment.
- For children receiving DTaP vaccine (alone or combination vaccine): Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures), not attributable to another identifiable cause, within 7 days of administration of previous dose of DTP or DTaP.
- Received any other non-live vaccines within 14 days prior to enrollment or any other live vaccines within 28 days prior to enrollment.
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 |
|---|---|---|
| mRNA COVID-19 VaccineAlso: Pfizer COVID-19 Vaccine, Moderna COVID-19 VaccineACIP Recommended Vaccine | Biological | Sequential vaccination arm, Simultaneous vaccination arm |
| Routine Childhood VaccinationsAlso: Pneumococcal, DTaP, Haemophilus Influenzae Type B, MMR, Varicella, MMRV, Hepatitis A, Inactivated Poliovirus, Hepatitis B, Rotavirus, Influenza vaccinesACIP Recommended Vaccines | Biological | Sequential vaccination arm, Simultaneous vaccination arm |
Primary outcome
Number of Participants With Fever Following Vaccination
Time frame: 2 Days Post-Administration
Number 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.
16 secondary outcomes
Number of Participants With Fever Following Visit 1
Time frame: 2 Days Post Visit 1
Number of Participants With Fever Following Visit 2
Time frame: 2 Days Post Visit 2
Number of Participants With Grade 2 and/or 3 Fever Following Visit 1 and Visit 2 Combined
Time frame: 2 Days Post Administration
Number of Participants With Grade 2 and/or 3 Fever Following Visit 1
Time frame: 2 Days Post Visit 1
Number of Participants With Grade 2 and/or 3 Fever Following Visit 2
Time frame: 2 Days Post Visit 2
Number of Participants With Medical Care Utilization for Fever - Visit 1 and Visit 2 Combined
Time frame: 2 Days Post Administration
Number of Participants With Medical Care Utilization for Fever - Visit 1
Time frame: 2 Days Post Visit 1
Number of Participants With Medical Care Utilization for Fever- Visit 2
Time frame: 2 Days Post Visit 2
Number of Participants Who Received Antipyretics - Visit 1 and Visit 2 Combined
Time frame: 2 Days Post Administration
Number of Participants Who Received Antipyretics - Visit 1
Time frame: 2 Days Post Visit 1
Number of Participants Who Received Antipyretics - Visit 2
Time frame: 2 Days Post Visit 2
Number of Participants With Defined Systemic Reactogenicity Events at Visit 1, Ages 6-23 Months Old
Time frame: Up to 7 Days Post Visit 1
Number of Participants With Defined Systemic Reactogenicity Events at Visit 2, Ages 6-23 Months Old
Time frame: Up to 7 Days Post Visit 2
Number of Participants With Defined Systemic Reactogenicity Events at Visit 1, Ages 2-5 Years Old
Time frame: Up to 7 Days Post Visit 1
Number of Participants With Defined Systemic Reactogenicity Events at Visit 2, Ages 2-5 Years Old
Time frame: Up to 7 Days Post Visit 2
The Number of Individuals With At Least One Serious Adverse Event
Time frame: Up to 105 Days Post Administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Michael J Smith, MD principal investigator
Duke University
5 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 mRNA COVID-19 Vaccine and Routine Childhood Vaccinations in people with Fever After Vaccination and Fever, run by Duke University at 5 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 17 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 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 13 May 2026). 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?
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 13 May 2026.