Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX_COMBO)

protocol of a randomised controlled trial

Amanda Leach, Edward (Kim) MULHOLLAND, M Santosham, Paul Torzillo, Ngiare Brown, Peter McIntyre, Heidi Smith-Vaughan, Sue Skull, Anne Balloch, Ross Andrews, Jonathan Carapetis, J McDonnell, Vicki Krause, Peter Morris

    Research output: Contribution to journalComment/debateResearch

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    Abstract

    Introduction: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.

    Methods and analyses: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.

    Ethics and dissemination: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.
    Original languageEnglish
    Article numbere007247
    Pages (from-to)1-10
    Number of pages10
    JournalBMJ Open
    Volume5
    Issue number1
    DOIs
    Publication statusPublished - Jan 2015

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    Conjugate Vaccines
    Pneumococcal Vaccines
    Otitis Media
    Randomized Controlled Trials
    Northern Territory
    Appointments and Schedules
    Haemophilus influenzae
    Streptococcus pneumoniae
    Vaccines
    Tympanic Membrane Perforation
    Combined Vaccines
    Ethics Committees
    Nasopharynx
    Health
    Middle Ear
    Hearing Loss
    Ethics
    Parents
    PHiD-CV vaccine
    13-valent pneumococcal vaccine

    Cite this

    Leach, Amanda ; MULHOLLAND, Edward (Kim) ; Santosham, M ; Torzillo, Paul ; Brown, Ngiare ; McIntyre, Peter ; Smith-Vaughan, Heidi ; Skull, Sue ; Balloch, Anne ; Andrews, Ross ; Carapetis, Jonathan ; McDonnell, J ; Krause, Vicki ; Morris, Peter. / Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX_COMBO) : protocol of a randomised controlled trial. In: BMJ Open. 2015 ; Vol. 5, No. 1. pp. 1-10.
    @article{bdf20944f9c146a5b7927b6889daa037,
    title = "Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial",
    abstract = "Introduction: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.Methods and analyses: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.Ethics and dissemination: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.",
    author = "Amanda Leach and MULHOLLAND, {Edward (Kim)} and M Santosham and Paul Torzillo and Ngiare Brown and Peter McIntyre and Heidi Smith-Vaughan and Sue Skull and Anne Balloch and Ross Andrews and Jonathan Carapetis and J McDonnell and Vicki Krause and Peter Morris",
    note = "The PREVIX_COMBO trial is funded by the Australian National Health and Medical Research Council, NHMRC (Project Grant 605 810). The trial sponsor is the Menzies School of Health Research, Northern Territory, Australia.",
    year = "2015",
    month = "1",
    doi = "10.1136/bmjopen-2014-007247",
    language = "English",
    volume = "5",
    pages = "1--10",
    journal = "BMJ Open",
    issn = "2044-6055",
    publisher = "British Medical Journal Publishing Group (BMJ Publishing)",
    number = "1",

    }

    Leach, A, MULHOLLAND, EK, Santosham, M, Torzillo, P, Brown, N, McIntyre, P, Smith-Vaughan, H, Skull, S, Balloch, A, Andrews, R, Carapetis, J, McDonnell, J, Krause, V & Morris, P 2015, 'Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial', BMJ Open, vol. 5, no. 1, e007247, pp. 1-10. https://doi.org/10.1136/bmjopen-2014-007247

    Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX_COMBO) : protocol of a randomised controlled trial. / Leach, Amanda; MULHOLLAND, Edward (Kim); Santosham, M; Torzillo, Paul; Brown, Ngiare; McIntyre, Peter; Smith-Vaughan, Heidi; Skull, Sue; Balloch, Anne; Andrews, Ross; Carapetis, Jonathan; McDonnell, J; Krause, Vicki; Morris, Peter.

    In: BMJ Open, Vol. 5, No. 1, e007247, 01.2015, p. 1-10.

    Research output: Contribution to journalComment/debateResearch

    TY - JOUR

    T1 - Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX_COMBO)

    T2 - protocol of a randomised controlled trial

    AU - Leach, Amanda

    AU - MULHOLLAND, Edward (Kim)

    AU - Santosham, M

    AU - Torzillo, Paul

    AU - Brown, Ngiare

    AU - McIntyre, Peter

    AU - Smith-Vaughan, Heidi

    AU - Skull, Sue

    AU - Balloch, Anne

    AU - Andrews, Ross

    AU - Carapetis, Jonathan

    AU - McDonnell, J

    AU - Krause, Vicki

    AU - Morris, Peter

    N1 - The PREVIX_COMBO trial is funded by the Australian National Health and Medical Research Council, NHMRC (Project Grant 605 810). The trial sponsor is the Menzies School of Health Research, Northern Territory, Australia.

    PY - 2015/1

    Y1 - 2015/1

    N2 - Introduction: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.Methods and analyses: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.Ethics and dissemination: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.

    AB - Introduction: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.Methods and analyses: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.Ethics and dissemination: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.

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    U2 - 10.1136/bmjopen-2014-007247

    DO - 10.1136/bmjopen-2014-007247

    M3 - Comment/debate

    VL - 5

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    EP - 10

    JO - BMJ Open

    JF - BMJ Open

    SN - 2044-6055

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