Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever

This study has been completed.
Sponsor:
Collaborator:
Children Youth and Family Consortium
Information provided by (Responsible Party):
Ian M. Paul, M.D., M.Sc., Penn State University
ClinicalTrials.gov Identifier:
NCT00267293
First received: December 16, 2005
Last updated: May 8, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Fever
Drug: Acetaminophen
Drug: Ibuprofen
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • Child Temperature (Degrees C)Over 6 Hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    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.


Enrollment: 60
Study Start Date: January 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
At time 0 child is given an appropriate dose of Ibuprofen (10mg/kg)
Drug: Ibuprofen
Given for fever control 10 mg/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)
Drug: Acetaminophen
Given for fever control 15mg/kg
Drug: Ibuprofen
Given for fever control 10 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)
Drug: Acetaminophen
Given for fever control 15mg/kg
Drug: Ibuprofen
Given for fever control 10 mg/kg

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.

  Eligibility

Ages Eligible for Study:   6 Months to 7 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00267293

Locations
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Sponsors and Collaborators
Penn State University
Children Youth and Family Consortium
Investigators
Principal Investigator: Ian M Paul, MD Penn State Milton S. Hershey Children's Hospital
  More Information

Additional Information:
No publications provided by Penn State University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ian M. Paul, M.D., M.Sc., Professor of Pediatrics and Public Health Sciences, Penn State University
ClinicalTrials.gov Identifier: NCT00267293     History of Changes
Other Study ID Numbers: HY03-127
Study First Received: December 16, 2005
Results First Received: July 22, 2011
Last Updated: May 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Penn State University:
fever treatment
children

Additional relevant MeSH terms:
Fever
Body Temperature Changes
Signs and Symptoms
Acetaminophen
Ibuprofen
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014