Clinical trial NCT02294071: Prospective Comparative Study of the Efficacy of Common Antipyretic Treatments in Febrile Children
Official title: Prospective Comparative Study of the Efficacy of Common Antipyretic Treatments in Febrile Children
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Fever
Keywords: acetaminophen
ibuprofen
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2014-11-19
Enrollment: 120
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine in detail the immediate effects of three common treatments given to children with fevers to lower their temperature. Each child will be given either ibuprofen, acetaminophen, or a combination, and their temperature monitored at five-minute intervals. The temperature-lowering effects of each treatment will be compared to evaluate which is most effective.

Detailed description: There is no substantial evidence that a fever lower than 41°C is harmful to the welfare of an otherwise healthy child, although they can be dangerous to children already in critical condition \[1,2\]. However, fevers in healthy children commonly cause anxiety in parents and caregivers, so parents and physicians often give antipyretic medications to lower the fever \[3,4\]. Ibuprofen and acetaminophen are two of the most commonly used medications in children. Most major pediatric medical associations agree about appropriate dosages for children, but give no clear guidelines on whether ibuprofen or acetaminophen should be used \[3,5\]. Physicians commonly make the decision between the two based on their personal opinions of the efficacy and safety of the medications, or based on habit \[6\]. Survey data shows that more than half of physicians use combinations of both acetaminophen and ibuprofen to treat fever, either simultaneously or on an alternating schedule, with a variety of dosing patterns \[6\]. A majority of physicians believed there were established guidelines supporting this use, but in fact there are not \[6\].

Combining the two medications is widely theorized to improve effectiveness, but clinical trials comparing combination treatments to ibuprofen and/or acetaminophen alone have shown inconsistent results \[4,7-12\]. Several pharmacodynamic studies have shown that ibuprofen and acetaminophen both produce their largest effects on temperature within the first hour following dosage \[9,10,13-16\]. Despite this, only one study has been performed examining the change in temperature at intervals shorter than 30 minutes, and that study used substandard monitoring methods \[10\].

This study will use gold-standard monitoring methods to take temperatures every five minutes through the first one to four hours of treatment. Understanding the pattern of temperature change in the acute stages after dosing will help settle the debate about the optimal medication choice for treating childrens' fevers.

Eligibility criteria: Inclusion Criteria:

* fever between 38 and 41 Celsius (inclusive) on presentation to ER
* assessment by treating physician that patient requires antipyretic treatment

Exclusion Criteria:

* known allergy or hypersensitivity to either study medication
* received any antipyretic medication in past eight hours
* patient requires admission to hospital
* co-morbidities indicating increased risk of complication
* assessment by treating physician that patient is medically unsuitable for the study

Primary outcomes:
measure: temperature reduction from baseline
timeFrame: 4 hours
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Western University, Canada
name: Michael J Rieder, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Lee BH, Inui D, Suh GY, Kim JY, Kwon JY, Park J, Tada K, Tanaka K, Ietsugu K, Uehara K, Dote K, Tajimi K, Morita K, Matsuo K, Hoshino K, Hosokawa K, Lee KH, Lee KM, Takatori M, Nishimura M, Sanui M, Ito M, Egi M, Honda N, Okayama N, Shime N, Tsuruta R, Nogami S, Yoon SH, Fujitani S, Koh SO, Takeda S, Saito S, Hong SJ, Yamamoto T, Yokoyama T, Yamaguchi T, Nishiyama T, Igarashi T, Kakihana Y, Koh Y; Fever and Antipyretic in Critically ill patients Evaluation (FACE) Study Group. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Crit Care. 2012 Feb 28;16(1):R33. doi: 10.1186/cc11211.
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citation: Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database Syst Rev. 2013 Oct 30;2013(10):CD009572. doi: 10.1002/14651858.CD009572.pub2.
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citation: Vyas FI, Rana DA, Patel PM, Patel VJ, Bhavsar RH. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Perspect Clin Res. 2014 Jan;5(1):25-31. doi: 10.4103/2229-3485.124567.
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citation: Kramer LC, Richards PA, Thompson AM, Harper DP, Fairchok MP. Alternating antipyretics: antipyretic efficacy of acetaminophen versus acetaminophen alternated with ibuprofen in children. Clin Pediatr (Phila). 2008 Nov;47(9):907-11. doi: 10.1177/0009922808319967. Epub 2008 Jun 6.
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