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

doi:10.1136/bmj.a1302

Published 2 September 2008, doi:10.1136/bmj.a1302
Cite this as: BMJ 2008;337:a1302

Research

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

Alastair D Hay, consultant senior lecturer in primary health care¹, Céire Costelloe, trial coordinator¹, Niamh M Redmond, trial coordinator¹, Alan A Montgomery, senior lecturer in primary care research¹, Margaret Fletcher, reader in children’s nursing², Sandra Hollinghurst, senior lecturer in health economics¹, Tim J Peters, professor of primary care health services research¹

¹ Academic Unit of Primary Health Care, NIHR National School for Primary Care Research, Department of Community Based Medicine, University of Bristol, Bristol BS8 2AA, ² Faculty of Health and Social Care, University of West England, Bristol

Correspondence to: A D Hay alastair.hay{at}bristol.ac.uk

Objective To investigate whether paracetamol (acetaminophen)plus ibuprofen are superior to either drug alone for increasingtime without fever and the relief of fever associated discomfortin 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 withaxillary temperatures of at least 37.8°C and up to 41.0°C.

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

Main outcome measures Primary outcomes were the time withoutfever (<37.2°C) in the first four hours after the firstdose was given and the proportion of children reported as beingnormal on the discomfort scale at 48 hours. Secondary outcomeswere 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 ibuprofenwere superior to paracetamol for less time with fever in thefirst four hours (adjusted difference 55 minutes, 95% confidenceinterval 33 to 77; P<0.001) and may have been as good asibuprofen (16 minutes, –7 to 39; P=0.2). For less timewith fever over 24 hours, paracetamol plus ibuprofen were superiorto 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 fever23 minutes (2 to 45; P=0.025) faster than paracetamol alonebut no faster than ibuprofen alone (–3 minutes, 18 to–24; P=0.8). No benefit was found for discomfort or othersymptoms, although power was low for these outcomes. Adverseeffects did not differ between groups.

Conclusion Parents, nurses, pharmacists, and doctors wantingto use medicines to supplement physical measures to maximisethe time that children spend without fever should use ibuprofenfirst and consider the relative benefits and risks of usingparacetamol plus ibuprofen over 24 hours.

Trial registration Current Controlled Trials ISRCTN26362730 [controlled-trials.com] .

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to StumbleUpon StumbleUpon Add to Technorati Technorati Twitter What's this?

Relevant Articles

Is combining or alternating antipyretic therapy more beneficial than monotherapy for febrile children?: Mona Nabulsi
BMJ 2009 339: b3540. [Extract] [Full Text]

Ibuprofen increases soft tissue infections in children: Carlos A Calderon Ospina and Alejandra Salcedo
BMJ 2008 337: a1767. [Extract] [Full Text]

Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomised controlled trial: Sandra Hollinghurst, Niamh Redmond, Céire Costelloe, Alan Montgomery, Margaret Fletcher, Tim J Peters, and Alastair D Hay
BMJ 2008 337: a1490. [Abstract] [Full Text] [PDF]

Antipyretic treatment for feverish young children in primary care: Anthony Harnden
BMJ 2008 337: a1409. [Extract] [Full Text]

Temperature measured at the axilla compared with rectum in children and young people: systematic review: Jean V Craig, Gillian A Lancaster, Paula R Williamson, and Rosalind L Smyth
BMJ 2000 320: 1174-1178. [Abstract] [Full Text] [PDF]

Minimisation: the platinum standard for trials?: Tom Treasure and Kenneth D MacRae
BMJ 1998 317: 362-363. [Extract] [Full Text]

What worries parents when their preschool children are acutely ill, and why: a qualitative study: Joe Kai
BMJ 1996 313: 983-986. [Abstract] [Full Text]

This article has been cited by other articles:

Nabulsi, M. (2009). Is combining or alternating antipyretic therapy more beneficial than monotherapy for febrile children?. BMJ 339: b3540-b3540 [Full text]
(2008). Ibuprofen Is Superior to Acetaminophen for Treating Childhood Fever. JWatch Emergency Med. 2008: 5-5 [Full text]
(2008). Comparison of Acetaminophen, Ibuprofen, and Both Agents for Treatment of Fever in Children. JWatch Pediatrics 2008: 2-2 [Full text]
Ospina, C. A C., Salcedo, A. (2008). Ibuprofen increases soft tissue infections in children. BMJ 337: a1767-a1767 [Full text]
Hollinghurst, S., Redmond, N., Costelloe, C., Montgomery, A., Fletcher, M., Peters, T. J, Hay, A. D (2008). Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomised controlled trial. BMJ 337: a1490-a1490 [Abstract] [Full text]
Harnden, A. (2008). Antipyretic treatment for feverish young children in primary care. BMJ 337: a1409-a1409 [Full text]

Rapid Responses:

Read all Rapid Responses

Combining paracetamol and ibuprofen: Edward Purssell, et al.
bmj.com, 3 Sep 2008 [Full text]
Re: Combining paracetamol and ibuprofen: Umesh Prabhu
bmj.com, 4 Sep 2008 [Full text]
conclusion?: yogi sehgal
bmj.com, 5 Sep 2008 [Full text]
A validation of Street Wisdom: Andrew P Mimnagh
bmj.com, 6 Sep 2008 [Full text]
Paracetamol plus ibuprofen for the treatment of fever in children: Jaseem Siddiqui
bmj.com, 6 Sep 2008 [Full text]
absences in IBU+Para in children: Nicholas D Moore
bmj.com, 10 Sep 2008 [Full text]
Increased risk of soft tissue infections in children who take ibuprofen and ibuprofen and paracetamol: Carlos A Calderon Ospina, et al.
bmj.com, 11 Sep 2008 [Full text]
PITCH: an indication of the level of emotion in relation to childhood fevers.: Wouter Havinga
bmj.com, 11 Sep 2008 [Full text]
Paracetamol and Ibuprofen (or Dipyrone) 3 hours each: Leonardo C M Savassi, et al.
bmj.com, 12 Sep 2008 [Full text]
Be cautious to avoid over treatment!: Sen Devadathan
bmj.com, 18 Sep 2008 [Full text]
No numbers in the abstract: Trish Groves
bmj.com, 23 Sep 2008 [Full text]
Other dangers of NSAIDs: Marise A McQueen
bmj.com, 24 Sep 2008 [Full text]
PITCH conclusions need to be retracted by the BMJ: Wouter Havinga
bmj.com, 29 Sep 2008 [Full text]
some missed points: Gema Ponce Revilla
bmj.com, 11 Oct 2008 [Full text]
A missed opportunity.: Sharon Conroy
bmj.com, 16 Oct 2008 [Full text]