Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial.

BMJ (2008)

Alastair D Hay, consultant senior lecturer in primary health care,1 Ce´ire Costelloe, trial coordinator,1
Niamh M Redmond, trial coordinator,1 Alan A Montgomery, senior lecturer in primary care research,1
Margaret Fletcher, reader in children’s nursing,2 Sandra Hollinghurst, senior lecturer in health economics,1
Tim J Peters, professor of primary care health services research1


ABSTRACT
Objective To investigate whether paracetamol
(acetaminophen) plus ibuprofen are superior to either
drug alone for increasing time without fever and the relief
of fever associated discomfort in febrile children managed
at home.

Design Individually randomised, blinded, three arm trial.
Setting Primary care and households in England.
Participants Children aged between 6 months and 6 years
with axillary temperatures of at least 37.8°C and up to
41.0°C.

Intervention Advice on physical measures to reduce
temperature and the provision of, and advice to give,
paracetamol plus ibuprofen, paracetamol alone, or
ibuprofen alone.

Main outcome measures Primary outcomes were the time
without fever (<37.2°C) in the first four hours after the first
dose was given and the proportion of children reported as
being normal on the discomfort scale at 48 hours.
Secondary outcomes were time to first occurrence of
normal temperature (fever clearance), time without fever
over 24 hours, fever associated symptoms, and adverse
effects.

Results On an intention to treat basis, paracetamol plus
ibuprofen were superior to paracetamol for less time with
fever in the first four hours (adjusted difference
55 minutes, 95% confidence interval 33 to 77; P<0.001)
and may have been as good as ibuprofen (16 minutes, −7
to 39; P=0.2). For less time with fever over 24 hours,
paracetamol plus ibuprofen were superior to paracetamol
(4.4 hours, 2.4 to 6.3; P<0.001) and to ibuprofen (2.5
hours, 0.6 to 4.4; P=0.008). Combined therapy cleared
fever 23 minutes (2 to 45; P=0.025) faster than
paracetamol alone but no faster than ibuprofen alone
(−3 minutes, 18 to −24; P=0.8). No benefit was found for
discomfort or other symptoms, although power was low
for these outcomes. Adverse effects did not differ between
groups.

Conclusion Parents, nurses, pharmacists, and doctors
wanting to use medicines to supplement physical
measures to maximise the time that children spend
without fever should use ibuprofen first and consider the
relative benefits and risks of using paracetamol plus
ibuprofen over 24 hours.
Trial registration Current Controlled Trials
ISRCTN26362730.