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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

Tracking Information
First Submitted Date  ICMJE December 16, 2005
First Posted Date  ICMJE December 20, 2005
Results First Submitted Date  ICMJE July 22, 2011
Results First Posted Date  ICMJE May 9, 2012
Last Update Posted Date May 9, 2012
Study Start Date  ICMJE January 2006
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2012)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2005)
Determine if combination and alternating regimens of ibuprofen and acetaminophen are superior to ibuprofen alone for fever reduction.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2005)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever
Official Title  ICMJE Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fever
Intervention  ICMJE
  • Drug: Acetaminophen
    Given for fever control 15mg/kg
  • Drug: Ibuprofen
    Given for fever control 10 mg/kg
Study Arms  ICMJE
  • 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
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 8, 2012)
60
Original Enrollment  ICMJE
 (submitted: December 16, 2005)
120
Actual Study Completion Date  ICMJE June 2009
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 7 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00267293
Other Study ID Numbers  ICMJE HY03-127
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ian M. Paul, M.D., M.Sc., Penn State University
Study Sponsor  ICMJE Penn State University
Collaborators  ICMJE Children Youth and Family Consortium
Investigators  ICMJE
Principal Investigator: Ian M Paul, MD Penn State Milton S. Hershey Children's Hospital
PRS Account Penn State University
Verification Date May 2012

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