Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis chronic suppurative lung disease and bronchiectasis

Protocol for a randomised controlled trial

Kerry-Ann O'Grady, Keith Grimwood, Allan Cripps, Edward (Kim) MULHOLLAND, Peter Morris, Paul Torzillo, Nicholas Wood, Heidi Smith-Vaughan, Amber Revell, Andrew Wilson, Peter Van Asperen, Peter C Richmond, Ruth B Thornton, Sheree Rablin, Anne Chang

    Research output: Contribution to journalComment/debateResearchpeer-review

    Abstract

    Background: Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children.


    Methods: A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety.


    Discussion: As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

    Original languageEnglish
    Article number282
    Pages (from-to)1-11
    Number of pages11
    JournalTrials
    Volume14
    DOIs
    Publication statusPublished - 5 Sep 2013

    Fingerprint

    Conjugate Vaccines
    Bronchiectasis
    Chronic Bronchitis
    Lung Diseases
    Vaccines
    Haemophilus influenzae
    Randomized Controlled Trials
    Bronchitis
    Streptococcus pneumoniae
    Mucosal Immunity
    Protein S
    Insurance Benefits
    Random Allocation
    Haemophilus influenzae glpQ protein
    Saliva
    Cough
    Human Influenza
    Disease Progression
    Chronic Disease
    Pediatrics

    Cite this

    O'Grady, Kerry-Ann ; Grimwood, Keith ; Cripps, Allan ; MULHOLLAND, Edward (Kim) ; Morris, Peter ; Torzillo, Paul ; Wood, Nicholas ; Smith-Vaughan, Heidi ; Revell, Amber ; Wilson, Andrew ; Van Asperen, Peter ; Richmond, Peter C ; Thornton, Ruth B ; Rablin, Sheree ; Chang, Anne. / Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis chronic suppurative lung disease and bronchiectasis : Protocol for a randomised controlled trial. In: Trials. 2013 ; Vol. 14. pp. 1-11.
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    abstract = "Background: Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods: A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. Discussion: As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.",
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    author = "Kerry-Ann O'Grady and Keith Grimwood and Allan Cripps and MULHOLLAND, {Edward (Kim)} and Peter Morris and Paul Torzillo and Nicholas Wood and Heidi Smith-Vaughan and Amber Revell and Andrew Wilson and {Van Asperen}, Peter and Richmond, {Peter C} and Thornton, {Ruth B} and Sheree Rablin and Anne Chang",
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    Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis chronic suppurative lung disease and bronchiectasis : Protocol for a randomised controlled trial. / O'Grady, Kerry-Ann; Grimwood, Keith; Cripps, Allan; MULHOLLAND, Edward (Kim); Morris, Peter; Torzillo, Paul; Wood, Nicholas; Smith-Vaughan, Heidi; Revell, Amber; Wilson, Andrew; Van Asperen, Peter; Richmond, Peter C; Thornton, Ruth B; Rablin, Sheree; Chang, Anne.

    In: Trials, Vol. 14, 282, 05.09.2013, p. 1-11.

    Research output: Contribution to journalComment/debateResearchpeer-review

    TY - JOUR

    T1 - Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis chronic suppurative lung disease and bronchiectasis

    T2 - Protocol for a randomised controlled trial

    AU - O'Grady, Kerry-Ann

    AU - Grimwood, Keith

    AU - Cripps, Allan

    AU - MULHOLLAND, Edward (Kim)

    AU - Morris, Peter

    AU - Torzillo, Paul

    AU - Wood, Nicholas

    AU - Smith-Vaughan, Heidi

    AU - Revell, Amber

    AU - Wilson, Andrew

    AU - Van Asperen, Peter

    AU - Richmond, Peter C

    AU - Thornton, Ruth B

    AU - Rablin, Sheree

    AU - Chang, Anne

    PY - 2013/9/5

    Y1 - 2013/9/5

    N2 - Background: Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods: A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. Discussion: As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

    AB - Background: Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods: A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. Discussion: As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

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    KW - Pneumococcus vaccine

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    KW - adolescent

    KW - article

    KW - blood sampling

    KW - bronchiectasis

    KW - bronchitis

    KW - child

    KW - chronic lung disease

    KW - chronic suppurative lung disease

    KW - controlled study

    KW - disease exacerbation

    KW - double blind procedure

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    KW - Pneumonia, Pneumococcal

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    KW - Time Factors

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    U2 - 10.1186/1745-6215-14-282

    DO - 10.1186/1745-6215-14-282

    M3 - Comment/debate

    VL - 14

    SP - 1

    EP - 11

    JO - Trials

    JF - Trials

    SN - 1745-6215

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    ER -