Official Title: “Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: May 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Acetaminophen
  • Given for fever control 15mg/kg
• Drug: Ibuprofen
  • Given for fever control 10 mg/kg

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg)
• Experimental: B
  • At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) and an appropriate dose of Acetaminophen (15 mg/kg)
• Experimental: C
  • 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)

Primary Measures

• Determine if combination and alternating regimens of ibuprofen and acetaminophen are superior to ibuprofen alone for fever reduction.
  • Time Frame: 3 years
    Safety Issue?: No

Secondary Measures

• Determine if combination and alternating regimens of antipyretics are superior for improvement of the discomfort associated with febrile illnesses in childhood.
  • Time Frame: 3 years
    Safety Issue?: No
• Determine if combination and alternating regimens of antipyretics are as well tolerated as a single agent.
  • Time Frame: 3 years
    Safety Issue?: No

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 mellitus, 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Months

Maximum Age for this Clinical Trial: 7 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Penn State University

Overall Clinical Trial Officials and Contacts

Ian M Paul, MD Principal Investigator Penn State Milton S. Hershey Children's Hospital  

Overall Contact: Jessica Beiler, MPH 717-531-5656 jbeiler@psu.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00267293

Study ID Number: HY03-127

ClinicalTrials.gov Identifier: NCT00267293

Health Authority: United States: Institutional Review Board

Penn State Milton S. Hershey Children's Hospital Pediatric Clinical Research Office