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

doi: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

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

Child and Maternal Health

Research output: Contribution to journal › Comment/debate

20 Citations (Scopus)

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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 language	English
Article number	e007247
Pages (from-to)	1-10
Number of pages	10
Journal	BMJ Open
Volume	5
Issue number	1
DOIs	https://doi.org/10.1136/bmjopen-2014-007247
Publication status	Published - Jan 2015

Bibliographical 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/bmjopen-2014-007247Licence: CC BY-NC

5356101-oaFinal published version, 1.4 MBLicence: CC BY-NC

Cite this

Leach, A., MULHOLLAND, E., 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, 5(1), 1-10. Article e007247. https://doi.org/10.1136/bmjopen-2014-007247

@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 = jan,

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, E, 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

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.

UR - https://www.scopus.com/pages/publications/84921913831

U2 - 10.1136/bmjopen-2014-007247

DO - 10.1136/bmjopen-2014-007247

M3 - Comment/debate

SN - 2044-6055

VL - 5

SP - 1

EP - 10

JO - BMJ Open

JF - BMJ Open

IS - 1

M1 - e007247

ER -

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

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Single versus combination pneumococcal conjugate vaccines (13PCV and PHiD-CV) for high-risk Aboriginal children (COMBO)

Cite this

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

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Single versus combination pneumococcal conjugate vaccines (13PCV and PHiD-CV) for high-risk Aboriginal children (COMBO)

Cite this