Paracetamol and ibuprofen for the

treatment of fever in children: the

Paracetamol and ibuprofen for the treatment of

PITCH randomised controlled trial

AD Hay1*, NM Redmond1, C Costelloe,

AA Montgomery1, M Fletcher2,
S Hollinghurst1 and TJ Peters1
1
Academic Unit of Primary Health Care, NIHR National School for Primary
Care Research, Department of Community Based Medicine, University of
Bristol, Bristol, UK
2
Faculty of Health and Social Care, University of the West of England,
Bristol, UK

*Corresponding author
fever in children

Executive summary
Health Technology Assessment 2009; Vol. 13: No. 27
DOI: 10.3310/hta13270

Health Technology Assessment

NIHR HTA programme
www.hta.ac.uk
Executive summary: �Paracetamol and ibuprofen for the treatment of fever in children

Executive summary
Background Children were excluded if they required hospital
admission; were clinically dehydrated; had recently
Paracetamol and ibuprofen are increasingly used participated in another trial; had previously
together for fever, despite a lack of evidence participated in PITCH; had a known trial medicine
regarding their clinical effectiveness or cost- intolerance, allergy or contraindication; if they
effectiveness. had a chronic neurological disease; and/or if their
parents could not read or write English.
Objectives
1. To establish the relative clinical effectiveness Interventions
of both medicines compared with paracetamol The intervention was the provision of, and
and ibuprofen separately for time without fever advice to give, the medicines for up to 48 hours:
in young children who can be managed at paracetamol every 4–6 hours (maximum of four
home. doses in 24 hours) and ibuprofen every 6–8 hours
2. To assess the relative clinical effectiveness (maximum of three doses in 24 hours). Every
of both medicines with paracetamol and parent received two bottles, with at least one
ibuprofen separately for the relief of fever- containing an active medicine. Parents, research
associated discomfort. nurses and investigators were blinded to treatment
3. To use qualitative methods to optimise the allocation by the use of identically matched placebo
overall trial process and explore parents’ and medicines. The dose of medicine was determined
clinicians’ beliefs about the use, effectiveness by the child’s weight: paracetamol 15 mg/kg and
and side effects of paracetamol and ibuprofen. ibuprofen 10 mg/kg per dose.
4. To perform an economic evaluation from
the perspectives of the NHS and parents
comparing the cost and benefits of each Main outcome measures
treatment. Primary outcome measures were time without fever
5. To describe the natural history of fever. in the first 4 hours and fever-associated discomfort
at 48 hours, measured using continuous axillary
thermometry and a symptom diary respectively.
Design Secondary outcomes were fever clearance (time
to first apyrexial); time without fever during the
The trial design was a single-centre (multisite), first 24 hours; other fever-associated symptoms
individually randomised, blinded, three-arm trial (appetite, activity and sleep), digital axillary
comparing paracetamol and ibuprofen together temperature and adverse effects at 24 hours, 48
with paracetamol or ibuprofen separately. hours and day 5. Directs costs to the NHS and
parents were estimated at 48 hours and day 5;
we assumed that parents had bought the study
Setting medicines over the counter.
There were three recruitment settings, as follows:
‘local’ where research nurses were recruited from
NHS primary care sites; ‘remote’ where NHS sites Research findings
notified the study of potentially eligible children;
and ‘community’ where parents contacted the study For additional time without fever in the first 4
in response to local media advertisements. hours, use of both medicines was superior to use of
paracetamol alone [adjusted difference 55 minutes,
95% confidence interval (CI) 33 to 77 minutes;
Participants p < 0.001] and may have been as good as ibuprofen
We recruited children aged between 6 months (adjusted difference 16 minutes, 95% CI –6 to 39
and 6 years with fever ≥ 37.8°C and ≤ 41°C due minutes; p = 0.2). Both medicines together cleared
to an illness that could be managed at home.
 Health Technology Assessment 2009; Vol. 13: No. 27 (Executive summary)

the fever 23 minutes (95% CI 2–45 minutes; either monotherapy. However, if two medicines
p = 0.015) faster than paracetamol alone but no are used, we recommend that all dose times are
faster than ibuprofen alone (adjusted difference carefully recorded to avoid accidentally exceeding
–3 minutes, 95% CI 24–18 minutes; p = 0.8). For the maximum recommended dose. Manufacturers
additional time without fever in the first 24 hours, should consider supplying blank charts for this
both medicines were superior to paracetamol purpose. The economic analysis shows that the
(adjusted difference 4.4 hours, 95% CI 2.4–6.3 use of both medicines should not be discouraged
hours; p < 0.001) or ibuprofen (adjusted difference on the basis of cost to either parents or the NHS.
2.5 hours, 95% CI 0.6–4.5 hours; p = 0.008) Parents and clinicians should be aware that fever
alone. No reduction in discomfort or other fever- is a relatively short-lived symptom, but may
associated symptoms was found, although power have more serious prognostic implications than
was low for these outcomes. An exploratory analysis the other common symptom presentations of
showed that children with higher discomfort levels childhood.
had higher mean temperatures. No difference in
adverse effects was observed between treatment Recommendations for research
groups. The recommended maximum number (in order of priority)
of doses of paracetamol and ibuprofen in 24
hours was exceeded in 8% and 11% of children 1. Is a parent education programme that includes
respectively. information regarding the accurate dosing
(by weight) of antipyretics cost effective in
Over the 5-day study period, paracetamol and improving parents’ ability to care for children
ibuprofen together was the cheapest option for in the home?
the NHS due to the lower use of health-care
services: £14 [standard deviation (SD) £23] versus 2. Children’s infections are the single largest
£20 (SD £38) for paracetamol and £18 (SD £40) contributor to NHS workload. Improving
for ibuprofen. Both medicines were also cheapest parents’ confidence to care for children in the
for parents because the lower use of health care home, dose medicines accurately and to know
services resulted in personal saving on travel when to seek medical help could have major
costs and less time off work: £24 (SD £46) versus benefits for the NHS.
£26 (SD £63) for paracetamol and £30 (SD £91)
for ibuprofen. This more than compensated for 3. The evidence base for the general components
the extra cost of medication. However, statistical of an effective behavioural change intervention
evidence for these differences was weak due to lack is well established. Previous parent
of power. interventions providing written information
only regarding the management of common
Overall, a quarter of children were ‘back to illnesses demonstrated little change in their use
normal’ by 48 hours and one-third by day 5. of health services. The PITCH study suggested
After randomisation, five (3%) children were that the ‘dose by weight’ use of combined
admitted to hospital, two with pneumonia, two antipyretic medicines might be cost effective,
with bronchiolitis and one with a severe, but due to reductions in the use of primary care
unidentified ‘viral illness’. services when compared with the use of single
medicines.

Conclusions
Implications for health care Trial registration
Doctors, nurses and parents who want to use This trial is registered as ISRCTN 26362730.
medicines to treat young children who are unwell
with fever should be advised to use ibuprofen first
and to consider the relative risks (inadvertently
Publication
exceeding the maximum recommended dose)
and benefits (extra 2.5 hours without fever) of Hay AD, Redmond NM, Costelloe C, Montgomery
using paracetamol plus ibuprofen over 24 hours. AA, Fletcher M, Hollinghurst S et al. Paracetamol
Pragmatically, we speculate that if a child remains and ibuprofen for the treatment of fever in
unwell after a first dose of ibuprofen, subsequent children: the PITCH randomised controlled trial.
use of both medicines will be more effective than Health Technol Assess 2009;13(27).
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