10-Valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine (PHiD-CV10) versus 13-valent pneumococcal conjugate vaccine (PCV13) as a booster dose to broaden and strengthen protection from otitis media (PREVIX_BOOST) in Australian Aboriginal children: study protocol for a randomised controlled trial

Abstract

Introduction: Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are major otitis media pathogens that densely co-colonise the nasopharynx and infect the middle ear of Australian Aboriginal infants from very early in life. Our co-primary hypotheses are that at 18 months of age infants receiving 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) compared with those receiving 13-valent pneumococcal conjugate vaccine (PCV13) as a booster at 12 months of age will have higher antibody levels to Haemophilus influenzae protein D and that infants receiving PCV13 will have higher antibody levels to PCV13-only serotypes 3, 6A and 19A.

Methods and analyses: Our randomised controlled trial will enrol 270 Aboriginal children at 12 months of age to a booster dose of either PHiD-CV10 or PCV13. Children who completed the three-dose primary course schedules of PHiD-CV10 at 2, 4, 6 months of age; PCV13 at 2, 4, 6 months of age; or a combination schedule of PHiD-CV10 at 1, 2, 4 months of age plus PCV13 at 6 months of age are eligible. The co-primary assessor-blinded outcomes when the infants are 18 months of age are as follows: (a) IgG geometric mean concentration (GMC) and proportion with IgG ≥100 EU/mL for protein D, and (b) IgG GMC and the proportion with IgG ≥0.35 µg/mL for pneumococcal serotypes 3, 6A and 19A. Secondary immunogenicity comparisons of six primary and booster dose schedules of 10 shared serotypes at 18 months of age, nasopharyngeal carriage, all forms of otitis media, hearing loss and developmental milestones at 18, 24, 30 and 36 months of age will be reported.

Ethics and dissemination: Ethics committees of NT Department of Health, Menzies, WA Department of Health and WA Aboriginal Health approved the study. Results will be presented to communities, at conferences and published in peer-reviewed journals.

Trial registration number: NCT01735084.

Keywords: PCV13; PHiD-CV10; nasopharyngeal carriage; otitis media.

Conflict of interest statement

Competing interests: In the last 5 years, AJL and PM have served on an OM Advisory Board for GSK and have received GSK support for the clinical outreach training program. KM has served on Advisory Boards for GSK who provided in kind support for the Vietnam Pneumococcal trial, of which he is the PI. His group is involved in a collaborative research project with Pfizer on adult pneumonia in Mongolia, and they have received a small grant to support research capacity building in the paediatric hospitals in Ho Chi Minh City, Vietnam. MS has served on the Advisory Board of GSK and Pfizer. He is also co-investigator on projects funded by GSK and Pfizer. ABC serves on an independent data safety monitoring board for two unlicensed GSK vaccines studies currently under evaluation. DL has received support from Pfizer Australia to attend conferences and is an investigator on an investigator-initiated research grant that was funded by Pfizer Australia.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Flow diagram. APP, as per protocol; ITT, intention to treat; PCV13,13-valent pneumococcal conjugate vaccine; PHiD-CV10, 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine; _PPP=3 doses of Prevenar at 2, 4 and 6 months of age; _SSS=3 doses of Synflorix at 2, 4 and 6 months of age; SSSP=3 doses of Synflorix at 1, 2 and 4 months and 1 dose of Prevenar at 6 months; +=plus; P=Prevenar; S=Synflorix.