HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia

protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial

Anne Chang, Siew Moy Fong, Tsin Yeo, Robert S. Ware, Gabrielle Mccallum, Anna Nathan, Mong How Ooi, Jessie de Bruyne, Catherine A. Byrnes, Bilawara LEE, Nachal Nachiappan, Noorazlina Saari, Paul Torzillo, Heidi Smith-Vaughan, Peter Morris, John W. Upham, Keith Grimwood

Research output: Contribution to journalArticleResearchpeer-review

3 Downloads (Pure)

Abstract

Introduction: Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.

Methods and analysis: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are ‘clinical cure’ at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.

Ethics and dissemination: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children’s and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.
Original languageEnglish
Article numbere026411
Pages (from-to)1-9
Number of pages9
JournalBMJ Open
Volume9
Issue number4
DOIs
Publication statusPublished - 24 Apr 2019

Fingerprint

Bronchiectasis
Malaysia
Pneumonia
Amoxicillin
Respiratory Signs and Symptoms
Randomized Controlled Trials
Anti-Bacterial Agents
Clavulanic Acid
Research Ethics Committees
Thorax
Placebos
X-Rays
Northern Territory
Morus
School Health Services
Health
Microbial Drug Resistance
New Zealand
Research
Ethics

Cite this

Chang, Anne ; Fong, Siew Moy ; Yeo, Tsin ; Ware, Robert S. ; Mccallum, Gabrielle ; Nathan, Anna ; Ooi, Mong How ; de Bruyne, Jessie ; Byrnes, Catherine A. ; LEE, Bilawara ; Nachiappan, Nachal ; Saari, Noorazlina ; Torzillo, Paul ; Smith-Vaughan, Heidi ; Morris, Peter ; Upham, John W. ; Grimwood, Keith. / HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia : protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial. In: BMJ Open. 2019 ; Vol. 9, No. 4. pp. 1-9.
@article{8f7e128ed46e4326bde51d3be9031ad8,
title = "HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia: protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial",
abstract = "Introduction: Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.Methods and analysis: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are ‘clinical cure’ at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.Ethics and dissemination: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children’s and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.",
author = "Anne Chang and Fong, {Siew Moy} and Tsin Yeo and Ware, {Robert S.} and Gabrielle Mccallum and Anna Nathan and Ooi, {Mong How} and {de Bruyne}, Jessie and Byrnes, {Catherine A.} and Bilawara LEE and Nachal Nachiappan and Noorazlina Saari and Paul Torzillo and Heidi Smith-Vaughan and Peter Morris and Upham, {John W.} and Keith Grimwood",
year = "2019",
month = "4",
day = "24",
doi = "10.1136/bmjopen-2018-026411",
language = "English",
volume = "9",
pages = "1--9",
journal = "BMJ Open",
issn = "2044-6055",
publisher = "British Medical Journal Publishing Group (BMJ Publishing)",
number = "4",

}

Chang, A, Fong, SM, Yeo, T, Ware, RS, Mccallum, G, Nathan, A, Ooi, MH, de Bruyne, J, Byrnes, CA, LEE, B, Nachiappan, N, Saari, N, Torzillo, P, Smith-Vaughan, H, Morris, P, Upham, JW & Grimwood, K 2019, 'HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia: protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial', BMJ Open, vol. 9, no. 4, e026411, pp. 1-9. https://doi.org/10.1136/bmjopen-2018-026411

HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia : protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial. / Chang, Anne; Fong, Siew Moy; Yeo, Tsin; Ware, Robert S.; Mccallum, Gabrielle; Nathan, Anna; Ooi, Mong How; de Bruyne, Jessie; Byrnes, Catherine A.; LEE, Bilawara; Nachiappan, Nachal; Saari, Noorazlina; Torzillo, Paul; Smith-Vaughan, Heidi; Morris, Peter; Upham, John W.; Grimwood, Keith.

In: BMJ Open, Vol. 9, No. 4, e026411, 24.04.2019, p. 1-9.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia

T2 - protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial

AU - Chang, Anne

AU - Fong, Siew Moy

AU - Yeo, Tsin

AU - Ware, Robert S.

AU - Mccallum, Gabrielle

AU - Nathan, Anna

AU - Ooi, Mong How

AU - de Bruyne, Jessie

AU - Byrnes, Catherine A.

AU - LEE, Bilawara

AU - Nachiappan, Nachal

AU - Saari, Noorazlina

AU - Torzillo, Paul

AU - Smith-Vaughan, Heidi

AU - Morris, Peter

AU - Upham, John W.

AU - Grimwood, Keith

PY - 2019/4/24

Y1 - 2019/4/24

N2 - Introduction: Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.Methods and analysis: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are ‘clinical cure’ at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.Ethics and dissemination: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children’s and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.

AB - Introduction: Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.Methods and analysis: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are ‘clinical cure’ at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.Ethics and dissemination: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children’s and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85065241493&origin=inward&txGid=4afde69b454c36252c6322d47816dd3c

U2 - 10.1136/bmjopen-2018-026411

DO - 10.1136/bmjopen-2018-026411

M3 - Article

VL - 9

SP - 1

EP - 9

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 4

M1 - e026411

ER -