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Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever

Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00267293
Enrollment
60
Registered
2005-12-20
Start date
2006-01-31
Completion date
2009-06-30
Last updated
2012-05-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fever

Keywords

fever treatment, children

Brief summary

Currently, when a child has fever either ibuprofen (e.g. Motrin, Advil) or acetaminophen (e.g. Tylenol) is given. Both Ibuprofen and Acetaminophen are approved for over the counter use for treatment of fever by the Food and Drug Administration (FDA). This study hopes to determine whether giving both medications together is better than giving one medication alone for the treatment of fever.

Detailed description

Despite a lack of evidence to support their fears, a majority of parents, pediatricians, and pediatric nurses believe that fever can be dangerous to a child. This fever phobia has caused a majority of caregivers to aggressively treat fever with antipyretics such as ibuprofen and acetaminophen, often in combination. Although there is scant data to support the use of these medications together for fever control and none using alternating regimens, it was recently reported that 50% of pediatricians and 70% of pediatricians with less than 5 years of experience advise parents to alternate acetaminophen and ibuprofen as an attempt to achieve maximal antipyresis. While a combination of aspirin (no longer used for antipyresis in children) and acetaminophen has been shown to be superior to either agent alone for fever reduction, these data cannot be extrapolated to the pairing of ibuprofen and acetaminophen. There is evidence that combinations of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are more effective for the treatment of pain and can reduce opioid use when compared with a single agent. Improved activity and alertness in children have been reported after antipyretic administration. It is believed that acetaminophen and ibuprofen may be safely used together because the two medications have significantly different pathways of metabolism that are not affected by each other, and have been used abroad in combination form for over a decade. Both acetaminophen and ibuprofen have been shown to be safe when given individually or together in recommended doses for short term use. There are no reports of adverse effects from combination therapy with standard doses. In addition, while it now appears that fever itself is probably a protective physiologic response, under different circumstances it has the potential to be harmful. Fever increases the metabolic rate approximately 10% for every 1 degree C rise in body temperature. The myocardial depression,orthostatic dysfunction, and increases in oxygen consumption, respiratory minute volume, and respiratory quotient that occur may not be tolerated by all patients including some children. Because of the ubiquitous nature of the problem, childhood fever, this study has the potential to immediately impact the way clinicians and parents treat children with fever. If the combination regimens are not shown to be superior, it could limit improper medication administration and overdose. If it is superior, the combination of medications may improve other symptoms associated with fever such as discomfort. Either way, it will fill the gap that exists in the evidence-based approach to the management of childhood fever and immediately impact current practice.

Interventions

DRUGAcetaminophen

Given for fever control 15mg/kg

DRUGIbuprofen

Given for fever control 10 mg/kg

Sponsors

Children Youth and Family Consortium
CollaboratorOTHER
Penn State University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
6 Months to 7 Years
Healthy volunteers
Yes

Inclusion criteria

* Age 6 months - 7 years of age at time of the fever. * Initial temperature of 38.0C (100.4F) or more. * Ability to cooperate with serial temporal artery temperature measurements. * Ability to take medications by mouth. * Willingness of the child's guardian/sponsor to give informed consent

Exclusion criteria

* Patients who have received acetaminophen within 6 hours of presentation, or ibuprofen, aspirin, or other non-steroidal anti-inflammatory medications within 8 hours of presentation. * Patients \>=3 years of age that have received narcotics in the previous 24 hours. * Children with weight \>60 kg. Treatment of children with weights \>60 kg will result in greater than recommended adult doses of the medications. * History of adverse reaction to any study medication ingredient. * History of diabetes mellitis, renal dysfunction, hepatic dysfunction, or thrombocytopenia. * Presence of moderate or severe dehydration. * Inclusion in the trial on 3 previous occasions * Medical judgment that the severity of the underlying illness prohibits inclusion.

Design outcomes

Primary

MeasureTime frameDescription
Child Temperature (Degrees C)Over 6 Hours6 hoursTemperature was measured hourly using a temporal thermometer to monitor the child's temperature in degrees C. Temperature of 38 degrees C or higher was considered febrile.

Countries

United States

Participant flow

Participants by arm

ArmCount
Group A: Ibuprofen Alone
Time 0 Ibuprofen (10mg/kg)given. Temperature in °C measured hourly for 6 hours.
20
Group B: Ibuprofen and Acetaminophen
time 0 child Ibuprofen (10mg/kg) and Acetaminophen (15 mg/kg)given. Temperature in °C measured hourly for 6 hours.
20
Group C: Ibuprofen Then Acetaminophen
Time 0 child is given Ibuprofen (10mg/kg) and at time 3 hours is given (15 mg/kg. Temperature in °C measured hourly for 6 hours.
20
Total60

Baseline characteristics

CharacteristicGroup B: Ibuprofen and AcetaminophenGroup C: Ibuprofen Then AcetaminophenGroup A: Ibuprofen AloneTotal
Age, Categorical
<=18 years
20 Participants20 Participants20 Participants60 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
0 Participants0 Participants0 Participants0 Participants
Age Continuous3.0 years
STANDARD_DEVIATION 1.9
4.0 years
STANDARD_DEVIATION 2.8
3.2 years
STANDARD_DEVIATION 1.9
3.4 years
STANDARD_DEVIATION 2.2
Region of Enrollment
United States
20 participants20 participants20 participants60 participants
Sex: Female, Male
Female
10 Participants13 Participants8 Participants31 Participants
Sex: Female, Male
Male
10 Participants7 Participants12 Participants29 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 200 / 200 / 20
serious
Total, serious adverse events
0 / 200 / 200 / 20

Outcome results

Primary

Child Temperature (Degrees C)Over 6 Hours

Temperature was measured hourly using a temporal thermometer to monitor the child's temperature in degrees C. Temperature of 38 degrees C or higher was considered febrile.

Time frame: 6 hours

Population: Analysis was ITT per sample size calculation at 80% power.

ArmMeasureValue (MEAN)Dispersion
Group A: Ibuprofen AloneChild Temperature (Degrees C)Over 6 Hours38.5 degrees CelciusStandard Deviation 1.5
Group B: Ibuprofen and AcetaminophenChild Temperature (Degrees C)Over 6 Hours37.2 degrees CelciusStandard Deviation 0.6
Group C: Ibuprofen Then AcetaminophenChild Temperature (Degrees C)Over 6 Hours36.9 degrees CelciusStandard Deviation 0.3
Comparison: Power for 80%p-value: <0.001Mixed Models Analysis
p-value: <0.0001Chi-squared

Source: ClinicalTrials.gov · Data processed: Mar 30, 2026