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

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    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.
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    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",
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    language = "English",
    volume = "9",
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    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

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    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.

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