Fever
Conditions
Keywords
Acetaminophen, Vaccination, Immunization
Brief summary
The purpose of this study is to see whether giving acetaminophen (the medicine in Tylenol) for routine infant vaccinations is helpful in preventing fever or other symptoms.
Detailed description
Post-vaccination fever occurs in up to 40% of infants receiving routinely recommended childhood vaccinations. Although serious events are rare, post-vaccination fever causes discomfort for the child, can lead to medical utilization, can rarely result in febrile seizure, and can cause a working parent to miss time from their job to care for a febrile infant who cannot attend day care. The benefits of acetaminophen prophylaxis for infants receiving current vaccinations, in terms of reduction of discomfort for the child, improvement of quality-of-life indicators for the parent, or reduction of medical utilization, have not been measured. This randomized, blinded, placebo-controlled trial will assess the efficacy of prophylaxis with acetaminophen in prevention of fever following routine childhood immunizations.
Interventions
DRUGAcetaminophen
Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
OTHERplacebo
Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Sponsors
Centers for Disease Control and Prevention
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 9 Months
Healthy volunteers
Yes
Inclusion criteria
1. Child is a current Group Health enrollee. 2. Child will be seen at a Group Health clinic for a Well Child visit that is expected to include 2 or more vaccines after 6 wks and before 10 months of age.
Exclusion criteria
1. If child was born at less than 36 weeks of gestation, the child is not eligible until 4 months of age or older. 2. If the child's birth weight was less than 5.5 pounds (2500 grams), the child is not eligible until 4 months of age or older.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fever >=38C Within 32 Hours of Vaccination. | Fever within 32 hours following vaccination | Fever, defined as rectal temperature \>=38C within 32 hours of vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Assignment Unblinded | At any time during participation in the study | The need for unblinding at any time during the study |
| Medical Utilization | Within 32 hours of vaccination. | Telephone calls to the consulting nurse or the child's physician that were made due to concerns regarding an acute illness, fever, or possible vaccine reaction and outpatient, urgent care, and emergency room visits that were for evaluation of an acute illness, fever, or a possible vaccine reaction, within 32 hours of vaccination. |
| Infant Fussiness | Within 32 hours of vaccination | Parents were asked to record level of fussiness (compared with the child's usual) within 32 hours of vaccination, using the categories much less than usual, less than usual, about usual, more than usual, and much more than usual. |
| Fever >=39C Within 32 Hours of Vaccination. | Fever within 32 hours following vaccination | Fever, defined as rectal temperature \>=39C within 32 hours of vaccination. |
| Infant Time Lost From Sleep | On the night following vaccinations | Parents were asked about their infant's sleep on the night following the vaccinations. They were asked to report whether their infant slept much less than usual, less than usual, about the usual amount, more than usual, or much more than usual on that night. |
| Parent Time Lost From Work | Through the day after vaccination | Parents were asked to report whether they were scheduled to work on the day of the vaccination visit (but following that visit) or the next day and, if so, whether they had to miss work to care for their infant because of fever, fussiness, or possible vaccine reaction on those days. |
| Parent Time Lost From Sleep | On the night following vaccinations | Parents were asked about their sleep on the night following the vaccinations. They were asked to report whether they slept much less than usual, less than usual, about the usual amount, more than usual, or much more than usual on that night. |
Countries
United States
Participant flow
Recruitment details
Recruitment and enrollment took place between May 2006 and September 2009. Children potentially eligible for study participation were identified from the Group Health data systems and parents were mailed a letter providing information on the study.
Pre-assignment details
No significant events followed participant enrollment prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Acetaminophen Subjects who were randomized to receive acetaminophen | 176 |
| Placebo Subjects who were randomized to receive placebo | 176 |
| Total | 352 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not take a dose of study product | 4 | 9 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Study product lost in mail | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Acetaminophen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 176 Participants | 176 Participants | 352 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 24.2 Weeks STANDARD_DEVIATION 4.7 | 24.8 Weeks STANDARD_DEVIATION 4.7 | 24.5 Weeks STANDARD_DEVIATION 4.7 |
| Region of Enrollment United States | 176 participants | 176 participants | 352 participants |
| Sex: Female, Male Female | 95 Participants | 77 Participants | 172 Participants |
| Sex: Female, Male Male | 81 Participants | 99 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 176 | 0 / 176 |
| serious Total, serious adverse events | 0 / 176 | 0 / 176 |
Outcome results
Primary
Fever >=38C Within 32 Hours of Vaccination.
Fever, defined as rectal temperature \>=38C within 32 hours of vaccination.
Time frame: Fever within 32 hours following vaccination
Population: Temperature values were missing for one subject in the acetaminophen group and two subjects in the placebo group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetaminophen | Fever >=38C Within 32 Hours of Vaccination. | 14 percentage of participants |
| Placebo | Fever >=38C Within 32 Hours of Vaccination. | 22 percentage of participants |
Comparison: The study sample size of 1000 children was selected to have 80% power to detect a 30% reduction in risk of the primary outcome of rectal temperature \>=38 following vaccination. In 2009, during the enrollment period of our trial, another paper reported the results of a randomized trial of acetaminophen prophylaxis in infants which found significantly lower immune responses to various vaccines in the acetaminophen group. In light of thse findings we elected to stop enrollment in our trial.p-value: 0.05395% CI: [0.41, 1.01]unadjusted Poisson regression
Secondary
Fever >=39C Within 32 Hours of Vaccination.
Fever, defined as rectal temperature \>=39C within 32 hours of vaccination.
Time frame: Fever within 32 hours following vaccination
Population: Temperature values were missing for one subject in the acetaminophen group and two subjects in the placebo group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetaminophen | Fever >=39C Within 32 Hours of Vaccination. | 0 percentage of participants |
| Placebo | Fever >=39C Within 32 Hours of Vaccination. | 2 percentage of participants |
p-value: 0.08Fisher Exact
Secondary
Infant Fussiness
Parents were asked to record level of fussiness (compared with the child's usual) within 32 hours of vaccination, using the categories much less than usual, less than usual, about usual, more than usual, and much more than usual.
Time frame: Within 32 hours of vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Acetaminophen | Infant Fussiness | Infant fussiness - About usual or less than usual | 42 percentage of participants |
| Acetaminophen | Infant Fussiness | Infant fussiness-More than or much more than usual | 58 percentage of participants |
| Acetaminophen | Infant Fussiness | Infant fussiness-Much more than usual | 10 percentage of participants |
| Placebo | Infant Fussiness | Infant fussiness - About usual or less than usual | 38 percentage of participants |
| Placebo | Infant Fussiness | Infant fussiness-More than or much more than usual | 62 percentage of participants |
| Placebo | Infant Fussiness | Infant fussiness-Much more than usual | 24 percentage of participants |
p-value: 0.00195% CI: [0.25, 0.7]unadjusted Poisson regression
Secondary
Infant Time Lost From Sleep
Parents were asked about their infant's sleep on the night following the vaccinations. They were asked to report whether their infant slept much less than usual, less than usual, about the usual amount, more than usual, or much more than usual on that night.
Time frame: On the night following vaccinations
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Acetaminophen | Infant Time Lost From Sleep | Infant sleep - About usual or more than usual | 78 percentage of participants |
| Acetaminophen | Infant Time Lost From Sleep | Infant sleep - Less than or much less than usual | 22 percentage of participants |
| Acetaminophen | Infant Time Lost From Sleep | Infant sleep - Much less than usual | 2 percentage of participants |
| Placebo | Infant Time Lost From Sleep | Infant sleep - About usual or more than usual | 81 percentage of participants |
| Placebo | Infant Time Lost From Sleep | Infant sleep - Less than or much less than usual | 19 percentage of participants |
| Placebo | Infant Time Lost From Sleep | Infant sleep - Much less than usual | 2 percentage of participants |
p-value: 195% CI: [0.25, 3.94]unadjusted Poisson regression
Secondary
Medical Utilization
Telephone calls to the consulting nurse or the child's physician that were made due to concerns regarding an acute illness, fever, or possible vaccine reaction and outpatient, urgent care, and emergency room visits that were for evaluation of an acute illness, fever, or a possible vaccine reaction, within 32 hours of vaccination.
Time frame: Within 32 hours of vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetaminophen | Medical Utilization | 3 percentage of participants |
| Placebo | Medical Utilization | 6 percentage of participants |
p-value: 0.1495% CI: [0.16, 1.28]unadjusted Poisson regression
Secondary
Parent Time Lost From Sleep
Parents were asked about their sleep on the night following the vaccinations. They were asked to report whether they slept much less than usual, less than usual, about the usual amount, more than usual, or much more than usual on that night.
Time frame: On the night following vaccinations
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Acetaminophen | Parent Time Lost From Sleep | Parent sleep - About usual or more than usual | 73 percentage of participants |
| Acetaminophen | Parent Time Lost From Sleep | Parent sleep - Much less than usual | 3 percentage of participants |
| Acetaminophen | Parent Time Lost From Sleep | Parent sleep - Less than or much less than usual | 27 percentage of participants |
| Placebo | Parent Time Lost From Sleep | Parent sleep - About usual or more than usual | 77 percentage of participants |
| Placebo | Parent Time Lost From Sleep | Parent sleep - Less than or much less than usual | 23 percentage of participants |
| Placebo | Parent Time Lost From Sleep | Parent sleep - Much less than usual | 5 percentage of participants |
p-value: 0.495% CI: [0.21, 1.88]unadjusted Poisson regression
Secondary
Parent Time Lost From Work
Parents were asked to report whether they were scheduled to work on the day of the vaccination visit (but following that visit) or the next day and, if so, whether they had to miss work to care for their infant because of fever, fussiness, or possible vaccine reaction on those days.
Time frame: Through the day after vaccination
Population: Refers to the number of participants for whom parents reported that they were scheduled to work on the day of the vaccination visit or the day following the child's vaccination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetaminophen | Parent Time Lost From Work | 4 percentage of participants |
| Placebo | Parent Time Lost From Work | 1 percentage of participants |
p-value: 0.1895% CI: [0.6, 14.34]unadjusted Poisson regression
Secondary
Study Assignment Unblinded
The need for unblinding at any time during the study
Time frame: At any time during participation in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetaminophen | Study Assignment Unblinded | 3 percentage of participants |
| Placebo | Study Assignment Unblinded | 9 percentage of participants |
p-value: 0.0295% CI: [0.12, 0.84]unadjusted Poisson regression