Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever

• 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: Penn State University
• Collaborator: Children Youth and Family Consortium
• Information provided by (Responsible Party): Ian M. Paul, M.D., M.Sc., Penn State University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fever	Drug: Acetaminophen; Drug: Ibuprofen	Phase 4

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ibuprofen Alone and in Combination With Acetaminophen for Treatment of Fever
• Study Start Date: January 2006
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 7 Years (Child)
• Sexes Eligible for Study: All
• 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

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:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Ian M. Paul, M.D., M.Sc., Professor of Pediatrics and Public Health Sciences, Penn State University
• ClinicalTrials.gov Identifier: NCT00267293
• Other Study ID Numbers: HY03-127
• First Posted: December 20, 2005
• Results First Posted: May 9, 2012
• Last Update Posted: May 9, 2012
• Last Verified: May 2012

Keywords provided by Ian M. Paul, M.D., M.Sc., Penn State University:

fever treatment; children

Additional relevant MeSH terms:

Fever; Body Temperature Changes; Acetaminophen; Ibuprofen; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action