Multi-site placebo-controlled randomised clinical trial to assess protection following oral immunisation with inactivated non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease

• Published in: Internal medicine journal Vol. 46; no. 6; pp. 684 - 693
• Main Authors: Clancy, R. L., Dunkley, M. L., Sockler, J., McDonald, C. F.
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.06.2016
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Australia; COPD; Disease Progression; Double-Blind Method; Female; Haemophilus Infections - prevention & control; Haemophilus influenzae; Haemophilus Vaccines - administration & dosage; Humans; immunisation; Logistic Models; Male; Middle Aged; non-typeable H. influenzae; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - microbiology; Quality of Life; Severity of Illness Index; Sputum - microbiology; Vaccination - methods; vaccine; non-typeable H. influenzae; vaccine; immunisation; COPD
• ISSN: 1444-0903; 1445-5994
• DOI: 10.1111/imj.13072

Background Previous studies identified factors that modify response to an oral non‐typeable Haemophilus influenzae (NTHi) vaccine in chronic obstructive pulmonary disease (COPD): severe COPD, moderate–severe exacerbations as end‐point and a threshold prevalence of NTHi in the study population. More data are needed to confirm parameters that influence clinical outcomes. Aims The primary aim was to determine the efficacy of an oral NTHi vaccine (HI‐164OV) in reducing the rate of exacerbations requiring systemic corticosteroids or hospitalisation in COPD. Secondary aims included effect on the proportion of patients experiencing such exacerbations, severity of infections and quality of life (St George Respiratory Questionnaire for COPD patients (SGRQ‐C)). Methods This multi‐centre, double‐blind, placebo‐controlled study was conducted at 21 Australian sites for 9 months in 2011. Results Three‐hundred and twenty subjects with COPD, FEV1 <60% predicted and ≥1 moderate–severe exacerbations in the previous 12 months were recruited. The primary and secondary end‐points for the intention‐to‐treat population aged 40–88 years were not achieved, and only 5% of subjects had an H. influenzae‐positive sputum sample. Subsequent exploratory analysis of patients <65 years (91 subjects) indicated protection with respect to the primary and most of the secondary end‐points, with SGRQ‐C symptom scores lower at 3 and 6 months. Conclusion Patients aged 40–88 years with moderate to severe COPD and low rates of H. influenzae‐positive sputum were not protected against exacerbations by HI‐1640V. Further studies are needed to confirm protection in subjects aged <65 years. Older age and low colonisation rates appear to affect adversely response to this vaccine.