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

BMJ 2008; 337 doi: https://doi.org/10.1136/bmj.a1302 (Published 02 September 2008) Cite this as: BMJ 2008;337:a1302
  1. Alastair D Hay, consultant senior lecturer in primary health care1,
  2. Céire Costelloe, trial coordinator1,
  3. Niamh M Redmond, trial coordinator1,
  4. Alan A Montgomery, senior lecturer in primary care research1,
  5. Margaret Fletcher, reader in children’s nursing2,
  6. Sandra Hollinghurst, senior lecturer in health economics1,
  7. Tim J Peters, professor of primary care health services research1
  1. 1Academic Unit of Primary Health Care, NIHR National School for Primary Care Research, Department of Community Based Medicine, University of Bristol, Bristol BS8 2AA
  2. 2Faculty of Health and Social Care, University of West England, Bristol
  1. Correspondence to: A D Hay alastair.hay{at}bristol.ac.uk
  • Accepted 4 July 2008

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.

Footnotes

  • We thank Avon, Gloucestershire, and Wiltshire NHS Direct; the Bristol general practitioner practices; the south Bristol walk-in centre; the emergency department of the Bristol Royal Hospital for Children; the children and parents who participated; the South West Medicines for Children Local Research Network; the research nurse team W Horseman, J Farrimond, R Powell, S Shatford, P Richards; the South West Medicines for Children Local Research Network nurse V Payne; W Patterson (trial coordinator); S Doohan and S Burke (project administrators); K Schroeder, M Weiss, and A Emond (co-applicants); Sara Whitburn (proof and background reading); K Pitcher (data entry and quality); the trial steering committee (AL Kinmonth, C Butler, J Peacock, M Blythe, and P Denyer); and the data monitoring and safety committee (R Bragonier, S Kerry, and J Chudleigh).

  • Contributors: ADH, AAM, MF, and TJP conceived the study and wrote the protocol. The research nurse team collected the data under the supervision of NMR, CC, and SH. AAM, CC, and TJP cleaned and analysed the data. CC, ADH, and TJP initially drafted the paper, with subsequent contributions from all authors. ADH is the guarantor.

  • Funding: National Institute for Health Research health technology assessment programme (project No 03/09/01). The final study design, data collection and analysis, interpretation of results, and paper writing was the sole responsibility of the authors. For the duration of the trial, ADH held a postdoctoral award from the National Coordinating Centre for Research Capacity Development, Department of Health. The views and opinions expressed in this paper do not necessarily reflect those of the funding bodies. The active drugs and placebos were purchased from Pfizer and DHP Investigational Medicinal Products, respectively. Neither had any other role in the design, conduct, analysis, or reporting of the trial.

  • Competing interests: None declared.

  • Ethical approval: Bath research ethics committee (reference No 04/Q2001/197).

  • Provenance and peer review: Not commissioned; externally peer reviewed.

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