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

Trials

Anne B Chang²  Sheree Rablin^1,10  Ruth Thornton¹  Peter Richmond¹  Peter Van Asperen³  Andrew Wilson⁶  Amber Revell²  Heidi Smith-Vaughan²  Nicholas Wood⁷  Paul J Torzillo⁵  Peter Morris⁸  Edward K Mulholland⁹  Allan Cripps⁴  Keith Grimwood^1,10  Kerry-Ann F O’Grady^1,10 

[1] Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, WA, Australia;Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia;Department of Respiratory Medicine, The Children’s Hospital at Westmead and Sydney Medical School, University of Sydney, Sydney, NSW, Australia;School of Medicine, Griffith University, Gold Coast, QLD, Australia;Royal Prince Alfred Hospital, Sydney, NSW, Australia;Department of Respiratory Medicine, Princess Margaret Hospital, Perth, WA, Australia;National Centre for Immunisation Research & Surveillance, University of Sydney, Westmead, NSW, Australia;Department of Paediatrics, Royal Darwin Hospital, Darwin, NT, Australia;London School of Hygiene & Tropical Medicine, London, UK;Queensland Children’s Medical Research Institute, Royal Children’s Hospital, The University of Queensland, Brisbane, QLD, Australia

关键词: Streptococcus pneumoniae;    Respiratory exacerbations;    Randomised controlled trial;    Protracted bacterial bronchitis;    Pneumococcal conjugate vaccines;    Non-typeable Haemophilus influenzae;    Chronic suppurative lung disease;    Child;    Bronchiectasis;   

Others  :  1093108
DOI  :  10.1186/1745-6215-14-282

 received in 2013-01-18, accepted in 2013-08-23,  发布年份 2013

【 摘 要 】

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.

Trial registration

Australia and New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12612000034831.

【 授权许可】

   
2013 O’Grady et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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