Azithromycin for Indigenous children with bronchiectasis

study protocol for a multi-centre randomized controlled trial

Patricia Valery, Peter Morris, Keith Grimwood, Paul Torzillo, C Byrnes, Ian Brent Masters, Paul Bauert, Gabrielle Mccallum, Charmaine Mobberley, Anne Chang

    Research output: Contribution to journalArticleResearchpeer-review

    5 Downloads (Pure)

    Abstract

    Background: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis.

    Methods/design: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ?6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms.

    Discussion: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children.

    Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.
    Original languageEnglish
    Pages (from-to)1-9
    Number of pages9
    JournalBMC Pediatrics
    Volume12
    Issue number122
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    Azithromycin
    Bronchiectasis
    Randomized Controlled Trials
    Lung
    Anti-Bacterial Agents
    New Zealand
    Cystic Fibrosis
    Medical Records
    Placebos
    Maintenance
    Pacific Islands
    Nasopharynx
    Controlled Clinical Trials
    Forced Expiratory Volume
    Microbial Drug Resistance
    Sputum
    Informed Consent
    Lung Diseases
    Registries
    Fibrosis

    Cite this

    Valery, Patricia ; Morris, Peter ; Grimwood, Keith ; Torzillo, Paul ; Byrnes, C ; Masters, Ian Brent ; Bauert, Paul ; Mccallum, Gabrielle ; Mobberley, Charmaine ; Chang, Anne. / Azithromycin for Indigenous children with bronchiectasis : study protocol for a multi-centre randomized controlled trial. In: BMC Pediatrics. 2012 ; Vol. 12, No. 122. pp. 1-9.
    @article{0f45e778a6b74fe4aaae4d74a46f2479,
    title = "Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial",
    abstract = "Background: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis.Methods/design: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ?6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms.Discussion: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children.Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.",
    keywords = "azithromycin, placebo, adverse outcome, antibiotic resistance, antibiotic therapy, article, Australia, bronchiectasis, child, clinical assessment, clinical protocol, controlled study, disease duration, disease exacerbation, disease severity, double blind procedure, education, female, forced expiratory volume, growth disorder, Haemophilus influenzae, human, indigenous people, major clinical study, male, medical record review, Moraxella catarrhalis, multicenter study, nasopharynx, New Zealand, nonhuman, preschool child, race, randomized controlled trial, respiratory distress, school child, sputum analysis, Staphylococcus aureus, Streptococcus pneumonia, Streptococcus pyogenes, treatment outcome, unspecified side effect, Anti-Bacterial Agents, Azithromycin, Bronchiectasis, Child, Child, Preschool, Clinical Protocols, Disease Progression, Double-Blind Method, Drug Administration Schedule, Follow-Up Studies, Humans, Infant, Intention to Treat Analysis, Kaplan-Meier Estimate, Oceanic Ancestry Group, Proportional Hazards Models, Treatment Outcome",
    author = "Patricia Valery and Peter Morris and Keith Grimwood and Paul Torzillo and C Byrnes and Masters, {Ian Brent} and Paul Bauert and Gabrielle Mccallum and Charmaine Mobberley and Anne Chang",
    year = "2012",
    doi = "10.1186/1471-2431-12-122",
    language = "English",
    volume = "12",
    pages = "1--9",
    journal = "BMC Pediatrics",
    issn = "1471-2431",
    publisher = "BioMed Central",
    number = "122",

    }

    Valery, P, Morris, P, Grimwood, K, Torzillo, P, Byrnes, C, Masters, IB, Bauert, P, Mccallum, G, Mobberley, C & Chang, A 2012, 'Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial', BMC Pediatrics, vol. 12, no. 122, pp. 1-9. https://doi.org/10.1186/1471-2431-12-122

    Azithromycin for Indigenous children with bronchiectasis : study protocol for a multi-centre randomized controlled trial. / Valery, Patricia ; Morris, Peter; Grimwood, Keith; Torzillo, Paul; Byrnes, C; Masters, Ian Brent; Bauert, Paul; Mccallum, Gabrielle; Mobberley, Charmaine; Chang, Anne.

    In: BMC Pediatrics, Vol. 12, No. 122, 2012, p. 1-9.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Azithromycin for Indigenous children with bronchiectasis

    T2 - study protocol for a multi-centre randomized controlled trial

    AU - Valery, Patricia

    AU - Morris, Peter

    AU - Grimwood, Keith

    AU - Torzillo, Paul

    AU - Byrnes, C

    AU - Masters, Ian Brent

    AU - Bauert, Paul

    AU - Mccallum, Gabrielle

    AU - Mobberley, Charmaine

    AU - Chang, Anne

    PY - 2012

    Y1 - 2012

    N2 - Background: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis.Methods/design: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ?6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms.Discussion: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children.Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.

    AB - Background: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis.Methods/design: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ?6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms.Discussion: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children.Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.

    KW - azithromycin

    KW - placebo

    KW - adverse outcome

    KW - antibiotic resistance

    KW - antibiotic therapy

    KW - article

    KW - Australia

    KW - bronchiectasis

    KW - child

    KW - clinical assessment

    KW - clinical protocol

    KW - controlled study

    KW - disease duration

    KW - disease exacerbation

    KW - disease severity

    KW - double blind procedure

    KW - education

    KW - female

    KW - forced expiratory volume

    KW - growth disorder

    KW - Haemophilus influenzae

    KW - human

    KW - indigenous people

    KW - major clinical study

    KW - male

    KW - medical record review

    KW - Moraxella catarrhalis

    KW - multicenter study

    KW - nasopharynx

    KW - New Zealand

    KW - nonhuman

    KW - preschool child

    KW - race

    KW - randomized controlled trial

    KW - respiratory distress

    KW - school child

    KW - sputum analysis

    KW - Staphylococcus aureus

    KW - Streptococcus pneumonia

    KW - Streptococcus pyogenes

    KW - treatment outcome

    KW - unspecified side effect

    KW - Anti-Bacterial Agents

    KW - Azithromycin

    KW - Bronchiectasis

    KW - Child

    KW - Child, Preschool

    KW - Clinical Protocols

    KW - Disease Progression

    KW - Double-Blind Method

    KW - Drug Administration Schedule

    KW - Follow-Up Studies

    KW - Humans

    KW - Infant

    KW - Intention to Treat Analysis

    KW - Kaplan-Meier Estimate

    KW - Oceanic Ancestry Group

    KW - Proportional Hazards Models

    KW - Treatment Outcome

    U2 - 10.1186/1471-2431-12-122

    DO - 10.1186/1471-2431-12-122

    M3 - Article

    VL - 12

    SP - 1

    EP - 9

    JO - BMC Pediatrics

    JF - BMC Pediatrics

    SN - 1471-2431

    IS - 122

    ER -