FeverPhase 4NCT00267293
Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever
A Phase 4 study testing Acetaminophen and Ibuprofen in people with Fever, run by Penn State University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months to 7 yearsHealthy volunteers can take part
- Conditions the study is for
- Fever
- What is being tested?
- Acetaminophen and Ibuprofen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Jun 2009
- 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 7 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
- Medical judgment that the severity of the underlying illness prohibits inclusion.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
About this study
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.
Read the 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.
- Conditions
- Fever
- Being tested
- Acetaminophen, Ibuprofen
- Keywords
- fever treatment, children
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Given for fever control 15mg/kg
IbuprofenDrug
Given for fever control 10 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) Receives: Drug: Ibuprofen |
| B | Experimental | At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) and an appropriate dose of Acetaminophen (15 mg/kg) Receives: Drug: Acetaminophen; Drug: Ibuprofen |
| C | Experimental | At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) and at time 3 hours is given an appropriate dose of Acetaminophen (15 mg/kg) Receives: Drug: Acetaminophen; Drug: Ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2005 (estimated)
- Study startJan 2006
- Primary completionJun 2009
- Study completionJun 2009
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 FeverStudies of the same condition, open and under way.
- More trials run by Penn State 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Penn State University
- Sponsor type
- University, hospital or other
- Collaborators
- Children Youth and Family Consortium
- Responsible party
- Principal investigator, Ian M. Paul, M.D., M.Sc., Penn State University
- Investigators
- Ian M Paul, MD, Principal investigator, Penn State Milton S. Hershey Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00267293
- Sponsor's protocol ID
- HY03-127
- Status last verified
- May 2012
- First submitted
- 16 Dec 2005
- Last updated
- 9 May 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Paul IM, Sturgis SA, Yang C, Engle L, Watts H, Berlin CM Jr. Efficacy of standard doses of Ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children. Clin Ther. 2010 Dec;32(14):2433-40. doi: 10.1016/j.clinthera.2011.01.006.
PubMed 21353111
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever
- ClinicalTrials.gov ID
- NCT00267293
- Acronym / sponsor ID
- HY03-127
- Conditions
- Fever
- Keywords
- fever treatment, children
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Penn State UniversityUniversity, hospital or other
- Collaborators
- Children Youth and Family Consortium
- Study start
- Jan 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 20 Dec 2005 (estimated)
- Results
- Posted 9 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: IbuprofenAt time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) |
| B | Experimental | Drug: Acetaminophen, Drug: IbuprofenAt time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) and an appropriate dose of Acetaminophen (15 mg/kg) |
| C | Experimental | Drug: Acetaminophen, Drug: IbuprofenAt time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) and at time 3 hours is given an appropriate dose of Acetaminophen (15 mg/kg) |
Who may qualify
- Ages
- 6 months to 7 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
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 |
|---|---|---|
| AcetaminophenGiven for fever control 15mg/kg | Drug | B, C |
| IbuprofenGiven for fever control 10 mg/kg | Drug | A, B, C |
Primary outcome
Child Temperature (Degrees C)Over 6 Hours
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21353111Paul IM, Sturgis SA, Yang C, Engle L, Watts H, Berlin CM Jr. Efficacy of standard doses of Ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children. Clin Ther. 2010 Dec;32(14):2433-40. doi: 10.1016/j.clinthera.2011.01.006.
- Penn State Milton S. Hershey Children's Hospital Pediatric Clinical Research OfficeLink provided by the sponsor.
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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.
Ian M Paul, MD principal investigator
Penn State Milton S. Hershey Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetaminophen and Ibuprofen in people with Fever, run by Penn State University at 1 site 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 6 inclusion and 6 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 9 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 9 May 2012). 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?
Child Temperature (Degrees C)Over 6 Hours (time frame: 6 hours). 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 NCT00267293, 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 9 May 2012.