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Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever

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ClinicalTrials.gov Identifier: NCT00267293
Recruitment Status : Completed
First Posted : December 20, 2005
Results First Posted : May 9, 2012
Last Update Posted : May 9, 2012
Sponsor:
Collaborator:
Children Youth and Family Consortium
Information provided by (Responsible Party):
Ian M. Paul, M.D., M.Sc., Penn State University

December 16, 2005
December 20, 2005
July 22, 2011
May 9, 2012
May 9, 2012
January 2006
June 2009   (Final data collection date for primary outcome measure)
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.
Determine if combination and alternating regimens of ibuprofen and acetaminophen are superior to ibuprofen alone for fever reduction.
Complete list of historical versions of study NCT00267293 on ClinicalTrials.gov Archive Site
Not Provided
  • Determine if combination and alternating regimens of antipyretics are superior for improvement of the discomfort associated with febrile illnesses in childhood.
  • Determine if combination and alternating regimens of antipyretics are as well tolerated as a single agent.
Not Provided
Not Provided
 
Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever
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.

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.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Fever
  • Drug: Acetaminophen
    Given for fever control 15mg/kg
  • Drug: Ibuprofen
    Given for fever control 10 mg/kg
  • Active Comparator: A
    At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg)
    Intervention: Drug: Ibuprofen
  • Experimental: B
    At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg) and an appropriate dose of Acetaminophen (15 mg/kg)
    Interventions:
    • Drug: Acetaminophen
    • Drug: Ibuprofen
  • 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)
    Interventions:
    • Drug: Acetaminophen
    • Drug: Ibuprofen
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
120
June 2009
June 2009   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
6 Months to 7 Years   (Child)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00267293
HY03-127
No
Not Provided
Not Provided
Ian M. Paul, M.D., M.Sc., Penn State University
Penn State University
Children Youth and Family Consortium
Principal Investigator: Ian M Paul, MD Penn State Milton S. Hershey Children's Hospital
Penn State University
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP