|Methods||Study design: randomized, double-blind and placebo-controlled clinical trial.|
Study dates and duration: November 2002 to April 2005.
Method of temperature measurement: rectal. Each patient used the same thermometer for the whole duration of study (SureTemp 679, Welch Allyn).
Time points measured in study: baseline rectal temperature at T0 then at hours 4, 5, 6, 7, 8.
|Participants||Number: 70 randomized|
Number of patients in each intervention: combined ibuprofen & paracetamol n=37, ibuprofen & placebo n=33.
Inclusion criteria: febrile inpatients aged 6 months – 14 years, with rectal temp ≥ 38.8 °C.
Exclusion criteria: vomiting, any medical or surgical condition that precluded oral drug administration, acute or chronic hepatic disease, malabsorption syndromes, acute or chronic renal disease with the exception of UTI, chronic metabolic disease, bleeding disorders, asthma, chronic neurological disease that may affect central thermoregulation, cancer, immune suppression, sepsis, critical medical status or known allergy to paracetamol or ibuprofen.
Age, mean years (SD): combined ibuprofen & paracetamol 3.7 (3.3), ibuprofen & placebo 3.6 (2.9)
Sex, male gender, n(%): combined ibuprofen & paracetamol 26 (70.3), Ibuprofen & placebo 19 (57.6)
Diagnoses: viral 62.9%, bacteria 27.1%, other 10%.
|Interventions||Control: ibuprofen 10 mg/kg followed by placebo 4 hours later|
Treatment group: single oral dose ibuprofen 10 mg/kg followed by single oral dose paracetamol 15 mg/kg 4 hours later
Proportion of children with normal body temperature at 6 hours (normal = rectal temp 36.5 °C to 37.9 °C)
Proportions of afebrile children in each group at 7 and 8 hours from baseline
Maximum decline in temperature during study period
Time to recurrence of fever
Mean temp changes from baseline at t= 4, 5, 6, 7 and 8h
The proportion of patients in each group with any adverse effect that may be related to either drug such as hypothermia, chilliness or gastrointestinal bleeding
Setting: multi-centre. This study was conducted in the paediatric inpatient services of two hospitals in Beirut: the American University of Beirut Medical Centre (AUBMC), which is a tertiary care facility; and Najjar Hospital, a secondary care facility.
Funding: this study was funded by the Medical Practice Plan of the Faculty of Medicine at the American University of Beirut, Grant number 686056. Gulf Pharmaceutical Industries, United Arab Emirates, donated all the drugs investigated.
|Risk of bias|
|Bias||Authors' judgement||Support for judgement|
|Random sequence generation (selection bias)||Low risk||Children enrolled in the study were assigned a random number by the hospital pharmacist according to a computer-generated random-number list, which was kept with the pharmacist until the end of the study.|
|Allocation concealment (selection bias)||Low risk||The allocation sequence was generated by one of the co-investigators who was not involved in subject recruitment, drug administration or outcome assessment.|
|Blinding of participants and personnel (performance bias) |
|Low risk||Subjects, parents and research assistant were blinded.|
|Blinding of outcome assessment (detection bias) |
|Low risk||Nurses responsible for drug administration and outcome assessment, treating physicians were blinded to patients' assignment.|
|Incomplete outcome data (attrition bias) |
|Low risk||Intent-to-treat analysis was planned.|
Loss to follow up: combined group 3%, ibuprofen group 0%.
|Selective reporting (reporting bias)||Low risk||All assessed outcomes were reported.|
|Other bias||Unclear risk||Forced to stop the trial before achieving the calculated sample size.|