Paul 2010

Methods	Study design: three‐arm, randomized, controlled trial. Study dates and duration: March 2006 to July 2009. Method of temperature measurement: temporal artery thermometer. Time points measured in study: hourly for 6 hours.
Participants	Number: 46 patients; among the 46 patients, 8 participated twice, 3 participated 3 times and 35 participated only once, contributing to 60 febrile episodes that were randomly assigned into the 3 treatment groups. Number of patients in each intervention: 20 episodes per group. Inclusion criteria: 6 months ‐ 8 years with temperature ≥38 °C. Required to demonstrate an ability to cooperate with serial temporal artery temperature measurements and to take medications by mouth Exclusion criteria: Received paracetamol within 6 hours of presentation or ibuprofen, aspirin or other NSAIDs within 8 hours of presentation. Other major exclusions included weight > 60kg (to avoid surpassing 600 mg of ibuprofen or 1000 mg of paracetamol in a single dose), a history of adverse reaction to any study medication ingredient, diabetes mellitus, renal dysfunction, hepatic dysfunction, thrombocytopenia, or presence of moderate or severe dehydration. Children were also excluded if medical judgement determined that the severity of the underlying illness prohibited inclusion or if the child had already participated in the trial on 3 previous occasions. Baseline characteristics: Age: n=46 (60 febrile episodes in 46 children). Aged 6 months to 8 years. Mean (SD) age = 3.4 (2.2) years Sex: 31/60 (51.7%) were girls Diagnoses: most common presenting diagnoses were upper respiratory infection (n=27), fever without a source (n=12), acute otitis media (n=8).
Interventions	Treatment group A: single dose ibuprofen 10 mg/kg (oral suspension 100 mg/5 mL) Treatment group B: single dose APAP 15 mg/kg (oral solution USP 160 mg/5 mL) plus ibuprofen 10 mg/kg Treatment group C: ibuprofen 10 mg/kg at the beginning of the study followed by 15 mg/kg of APAP 3 hours later
Outcomes	Primary: Effect of treatment on temperature over 6 hours
Notes	Location: USA Setting: one academic medical centre in Hershey, Pennsylvania, USA; patients recruited from outpatient clinics and child day‐care facilities. Funding: this study was supported by a research grant from the George L. Laverty Foundation and in part by a General clinical Research Centre grant from the National Institutes of Health and a CGRC Construction Grant awarded to the Pennsylvania State University College of Medicine. Disclosure: first author has been a paid consultant for the Consumer Healthcare Products Association, McNeil Consumer Healthcare, Novartis Consumer Health, Inc., Procter & Gamble, and Reckitt Benckiser Healthcare International Ltd., but no industry employees were involved in any aspect of the study. 11 patients participated ≥ 2 times (maximum 3 times).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Each child was randomly assigned to 1 of 3 treatment groups according to a computer‐generated log.
Allocation concealment (selection bias)	Unclear risk	Not specified.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	No attempt was made to blind the participants, however temperature is an objective measurement that should not be subject to bias from lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	No attempt was made to blind the research nurses, however temperature is an objective measurement that should not be subject to bias from lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No loss of participants during the study.
Selective reporting (reporting bias)	Low risk	All assessed outcomes were reported.
Other bias	Low risk