Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trialBMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f6041 (Published 25 October 2013) Cite this as: BMJ 2013;347:f6041
- Paul Little, general practitioner and professor of primary care research,
- Michael Moore, general practitioner and reader in primary care,
- Joanne Kelly, senior trial manager,
- Ian Williamson, general practitioner and senior lecturer in primary care,
- Geraldine Leydon, social scientist, principal research fellow,
- Lisa McDermott, research fellow,
- Mark Mullee, statistician, director research design service,
- Beth Stuart, research fellow
- on behalf of the PIPS investigators
- Correspondence to: P Little
- Accepted 23 September 2013
Objective To assess strategies for advice on analgesia and steam inhalation for respiratory tract infections.
Design Open pragmatic parallel group factorial randomised controlled trial.
Setting Primary care in United Kingdom.
Participants Patients aged ≥3 with acute respiratory tract infections.
Intervention 889 patients were randomised with computer generated random numbers in pre-prepared sealed numbered envelopes to components of advice or comparator advice: advice on analgesia (take paracetamol, ibuprofen, or both), dosing of analgesia (take as required v regularly), and steam inhalation (no inhalation v steam inhalation).
Outcomes Primary: mean symptom severity on days 2-4; symptoms rated 0 (no problem) to 7 (as bad as it can be). Secondary: temperature, antibiotic use, reconsultations.
Results Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval −0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, −0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5°C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen −0.40, −0.78 to −0.01; combination −0.47; −0.84 to −0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: −0.47, −0.76 to −0.18; combination: −0.04, −0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the combination (1.49, 0.98 to 2.18). Mild thermal injury with steam was documented for four patients (2%) who returned full diaries, but no reconsultations with scalding were documented.
Conclusion Overall advice to use steam inhalation, or ibuprofen rather than paracetamol, does not help control symptoms in patients with acute respiratory tract infections and must be balanced against the possible progression of symptoms during the next month for a minority of patients. Advice to use ibuprofen might help short term control of symptoms in those with chest infections and in children.
Trial registration ISRCTN 38551726.
We are grateful to all the general practitioners and practice nurses and particularly the patients who gave their time to this study.
University of Southampton: Paul Little, Ian Williamson, Mike Moore, Mark Mullee, Jo Kelly, Julie Hooper, Lisa McDermott, Gerry Leydon, Katherine Salisbury*, Emily Edwards*, Jennifer White*, Adam Nicholls*, Hannah Ebdon*, Susannah Gant* (*medical students at the time); Samantha Hall, Patient and Public (PPI) representative.
Contributors: All authors and Daniel Lane contributed significantly to the development of the protocol. All authors contributed to overseeing the management of the study, agreeing the analysis plan, and to the write-up of the paper. KS, EE, JW, AN, HE, and SG developed and piloted the initial study documents supervised by the trial team; PL had the initial idea, led the grant application, and the initial drafting of the paper and is guarantor. PL, MM, and BS performed the analysis. JK and JH performed day to day management of the study supervised by PL. Alastair Hay provide helpful comments on the analysis approach and the manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. Samantha Hall, PPI representative, kindly commented on the protocol and outcomes, and contributed to steering meetings
Funding: This study was funded by the National Institute for Health Research Programme Grants for Applied Research programme. This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research programme (grant ref No RP-PG-0407-10098). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study was approved by the Southampton and Southwest MREC number 06/Q1702/154 and all participants gave informed consent.
Declaration of transparency: PL affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Data sharing: No additional data available.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.