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Efficacy, safety, and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with Community-Acquired Pneumonia: a protocol for a randomised controlled trial (CAP-IT)

Efficacy, safety, and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with Community-Acquired Pneumonia: a protocol for a randomised controlled trial (CAP-IT)
Efficacy, safety, and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with Community-Acquired Pneumonia: a protocol for a randomised controlled trial (CAP-IT)
ntroduction Community-acquired pneumonia (CAP) is a common indication for antibiotic treatment in young children. Data are limited regarding the ideal dose and duration of amoxicillin, leading to practice variation which may impact on treatment failure and antimicrobial resistance (AMR). Community-Acquired Pneumonia: a randomIsed controlled Trial (CAP-IT) aims to determine the optimal amoxicillin treatment strategies for CAP in young children in relation to efficacy and AMR.

Methods and analysis The CAP-IT trial is a multicentre, randomised, double-blind, placebo-controlled 2×2 factorial non-inferiority trial of amoxicillin dose and duration. Children are enrolled in paediatric emergency and inpatient environments, and randomised to receive amoxicillin 70–90 or 35–50 mg/kg/day for 3 or 7 days following hospital discharge. The primary outcome is systemic antibacterial treatment for respiratory tract infection (including CAP) other than trial medication up to 4 weeks after randomisation. Secondary outcomes include adverse events, severity and duration of parent-reported CAP symptoms, adherence and antibiotic resistance. The primary analysis will be by intention to treat. Assuming a 15% primary outcome event rate, 8% non-inferiority margin assessed against an upper one-sided 95% CI, 90% power and 15% loss to follow-up, 800 children will be enrolled to demonstrate non-inferiority for the primary outcome for each of duration and dose.

Ethics and dissemination The CAP-IT trial and relevant materials were approved by the National Research Ethics Service (reference: 16/LO/0831; 30 June 2016). The CAP-IT trial results will be published in peer-reviewed journals, and in a report published by the National Institute for Health Research Health Technology Assessment programme. Oral and poster presentations will be given to national and international conferences, and participating families will be notified of the results if they so wish. Key messages will be constructed in partnership with families, and social media will be used in their dissemination.

Trial registration number ISRCTN76888927, EudraCT2016-000809-36.
2044-6055
Lyttle, Mark D.
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Bielicki, Julia
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Barratt, Sam
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Dunn, David
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Finn, Adam
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Harper, Lynda
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Jackson, Pauline
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Powell, Colin V.E.
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Roland, Damian
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Stohr, Wolfgang
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Sturgeon, Kate
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Wan, Mandy
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Little, Paul
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Faust, Saul
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Robotham, Julie
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Hay, Alastair D.
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Gibb, Diana M.
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Sharland, Mike
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Lyttle, Mark D.
8b37d5d4-9dd1-4dfa-b251-7b560f4994c7
Bielicki, Julia
2420819f-afd1-4231-9783-345d17df31cb
Barratt, Sam
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Dunn, David
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Finn, Adam
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Harper, Lynda
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Jackson, Pauline
f60719d6-5606-49ed-a961-95a42b515323
Powell, Colin V.E.
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Roland, Damian
bac42549-2249-4b39-b272-4d11f451574a
Stohr, Wolfgang
f8c99992-148a-4e92-972d-5a2bda497f24
Sturgeon, Kate
77414ac9-6cdb-437f-b782-1eebd5f2d5b7
Wan, Mandy
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Little, Paul
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Faust, Saul
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Robotham, Julie
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Hay, Alastair D.
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Gibb, Diana M.
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Sharland, Mike
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Lyttle, Mark D., Bielicki, Julia, Barratt, Sam, Dunn, David, Finn, Adam, Harper, Lynda, Jackson, Pauline, Powell, Colin V.E., Roland, Damian, Stohr, Wolfgang, Sturgeon, Kate, Wan, Mandy, Little, Paul, Faust, Saul, Robotham, Julie, Hay, Alastair D., Gibb, Diana M. and Sharland, Mike (2019) Efficacy, safety, and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with Community-Acquired Pneumonia: a protocol for a randomised controlled trial (CAP-IT). BMJ Open, 9 (5), [e029875]. (doi:10.1136/bmjopen-2019-029875).

Record type: Article

Abstract

ntroduction Community-acquired pneumonia (CAP) is a common indication for antibiotic treatment in young children. Data are limited regarding the ideal dose and duration of amoxicillin, leading to practice variation which may impact on treatment failure and antimicrobial resistance (AMR). Community-Acquired Pneumonia: a randomIsed controlled Trial (CAP-IT) aims to determine the optimal amoxicillin treatment strategies for CAP in young children in relation to efficacy and AMR.

Methods and analysis The CAP-IT trial is a multicentre, randomised, double-blind, placebo-controlled 2×2 factorial non-inferiority trial of amoxicillin dose and duration. Children are enrolled in paediatric emergency and inpatient environments, and randomised to receive amoxicillin 70–90 or 35–50 mg/kg/day for 3 or 7 days following hospital discharge. The primary outcome is systemic antibacterial treatment for respiratory tract infection (including CAP) other than trial medication up to 4 weeks after randomisation. Secondary outcomes include adverse events, severity and duration of parent-reported CAP symptoms, adherence and antibiotic resistance. The primary analysis will be by intention to treat. Assuming a 15% primary outcome event rate, 8% non-inferiority margin assessed against an upper one-sided 95% CI, 90% power and 15% loss to follow-up, 800 children will be enrolled to demonstrate non-inferiority for the primary outcome for each of duration and dose.

Ethics and dissemination The CAP-IT trial and relevant materials were approved by the National Research Ethics Service (reference: 16/LO/0831; 30 June 2016). The CAP-IT trial results will be published in peer-reviewed journals, and in a report published by the National Institute for Health Research Health Technology Assessment programme. Oral and poster presentations will be given to national and international conferences, and participating families will be notified of the results if they so wish. Key messages will be constructed in partnership with families, and social media will be used in their dissemination.

Trial registration number ISRCTN76888927, EudraCT2016-000809-36.

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Accepted/In Press date: 14 March 2019
e-pub ahead of print date: 22 May 2019
Published date: July 2019

Identifiers

Local EPrints ID: 430643
URI: http://eprints.soton.ac.uk/id/eprint/430643
ISSN: 2044-6055
PURE UUID: 368dfe17-35c0-4f72-9c3c-73c98f719688
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 07 May 2019 16:30
Last modified: 16 Mar 2024 07:48

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Contributors

Author: Mark D. Lyttle
Author: Julia Bielicki
Author: Sam Barratt
Author: David Dunn
Author: Adam Finn
Author: Lynda Harper
Author: Pauline Jackson
Author: Colin V.E. Powell
Author: Damian Roland
Author: Wolfgang Stohr
Author: Kate Sturgeon
Author: Mandy Wan
Author: Paul Little
Author: Saul Faust ORCID iD
Author: Julie Robotham
Author: Alastair D. Hay
Author: Diana M. Gibb
Author: Mike Sharland

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