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Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial
Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial

BACKGROUND: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups.

METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298).

FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis.

INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

FUNDING: National Institute for Health Research.

0140-6736
1417-1426
Little, Paul
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Francis, Nick A
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Stuart, Beth
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O'Reilly, Gilly
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Thompson, Natalie
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Becque, Taeko
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Hay, Alastair D
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Harnden, Anthony
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Yao, Guiqing
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Raftery, James
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Zhu, Shihua
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Little, Joseph
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Hookham, Charlotte
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Rowley, Kate
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Euden, Joanne
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Harman, Kim
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Coenen, Samuel
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Read, Robert C
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Butler, Christopher C
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Little, Paul
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O'Reilly, Gilly
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Read, Robert C
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Verheij, Theo
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Little, Paul, Francis, Nick A, Stuart, Beth, O'Reilly, Gilly, Thompson, Natalie, Becque, Taeko, Hay, Alastair D, Wang, Kay, Sharland, Michael, Harnden, Anthony, Yao, Guiqing, Raftery, James, Zhu, Shihua, Little, Joseph, Hookham, Charlotte, Rowley, Kate, Euden, Joanne, Harman, Kim, Coenen, Samuel, Read, Robert C, Woods, Catherine, Butler, Christopher C, Faust, Saul N, Leydon, Geraldine, Wan, Mandy, Hood, Kerenza, Whitehurst, Jane, Richards-Hall, Samantha, Smith, Peter, Thomas, Michael, Moore, Michael and Verheij, Theo (2021) Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial. Lancet (London, England), 398 (10309), 1417-1426. (doi:10.1016/S0140-6736(21)01431-8).

Record type: Article

Abstract

BACKGROUND: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups.

METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298).

FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis.

INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

FUNDING: National Institute for Health Research.

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ARTICtrialpaperLancetrevisedcleancopyv2 - Accepted Manuscript
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Accepted/In Press date: 21 June 2021
e-pub ahead of print date: 22 September 2021
Published date: 22 September 2021

Identifiers

Local EPrints ID: 451527
URI: http://eprints.soton.ac.uk/id/eprint/451527
ISSN: 0140-6736
PURE UUID: 28b27480-5b93-47a4-bbb2-9c5cda964c80
ORCID for Nick A Francis: ORCID iD orcid.org/0000-0001-8939-7312
ORCID for Beth Stuart: ORCID iD orcid.org/0000-0001-5432-7437
ORCID for Taeko Becque: ORCID iD orcid.org/0000-0002-0362-3794
ORCID for Kim Harman: ORCID iD orcid.org/0000-0002-5173-7753
ORCID for Robert C Read: ORCID iD orcid.org/0000-0002-4297-6728
ORCID for Saul N Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Geraldine Leydon: ORCID iD orcid.org/0000-0001-5986-3300
ORCID for Michael Moore: ORCID iD orcid.org/0000-0002-5127-4509

Catalogue record

Date deposited: 05 Oct 2021 19:25
Last modified: 27 Apr 2022 02:15

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Contributors

Author: Paul Little
Author: Nick A Francis ORCID iD
Author: Beth Stuart ORCID iD
Author: Gilly O'Reilly
Author: Natalie Thompson
Author: Taeko Becque ORCID iD
Author: Alastair D Hay
Author: Kay Wang
Author: Michael Sharland
Author: Anthony Harnden
Author: Guiqing Yao
Author: James Raftery
Author: Shihua Zhu
Author: Joseph Little
Author: Charlotte Hookham
Author: Kate Rowley
Author: Joanne Euden
Author: Kim Harman ORCID iD
Author: Samuel Coenen
Author: Robert C Read ORCID iD
Author: Catherine Woods
Author: Christopher C Butler
Author: Saul N Faust ORCID iD
Author: Mandy Wan
Author: Kerenza Hood
Author: Jane Whitehurst
Author: Samantha Richards-Hall
Author: Peter Smith
Author: Michael Thomas
Author: Michael Moore ORCID iD
Author: Theo Verheij

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