Clinical trial NCT00792051: Direct and Indirect Benefits of Influenza Vaccine Versus Placebo in Healthy Children
Official title: A Randomised Controlled Trial of the Effectiveness of Vaccinating Children to Reduce Household Transmission of Influenza
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Influenza Virus Infection
Keywords: influenza
vaccination
children
Influenza-like illness
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Research Fund for the Control of Infectious Diseases
name: Research Grants Council, Hong Kong
name: Centre for Health Protection, Hong Kong
First posted: 2008-11-17
Enrollment: 2800
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: While immunisation of school-age children against influenza is not recommended in Hong Kong, past experience in Japan and elsewhere suggests that immunisation of children may protect the wider community through its indirect transmission-limiting impact as well as the direct immunologic protection afforded vaccinated children themselves. We aim to assess whether vaccinating children against influenza protects vaccinees as well as their household contacts from infection.

Detailed description: Design and subjects: A double-blind randomised controlled trial of 800 subjects aged 6-17 drawn from the general population and their 2000 household contacts. The subjects will be randomised in a 3:2 ratio to the intervention and placebo groups, respectively. Serum samples will be collected from subjects pre- and 1 month post-vaccination, and after the influenza season. Serum samples will be collected from household contacts at baseline and at the end of the influenza season. During the follow-up period, subjects and household members will keep symptom diaries and those reporting influenza-like-illness will be offered free doctor consultations or home visits where we will arrange for collection of nose and throat swabs.

Study instruments: An antibody titre of ≥40 in the post-vaccine serum will be used to define seroprotection to those particular strains, while a four-fold or higher increase in antibody titres between baseline and end-of-season follow-up of the household contacts will define influenza infection during the season. Subjects and household contacts will be asked to keep symptom diaries, and during episodes of ILI we will collect nose and throat swabs for laboratory confirmation of influenza infection; the primary serology results will then be compared with clinical and laboratory-confirmed influenza episodes.

Interventions: 1 (intervention) inactivated influenza vaccine (Vaxigrip, Sanofi Pasteur); 2 (placebo) saline injection.

Main outcome measures: The proportions of subjects and household contacts with serology-confirmed influenza infection during follow-up among the 2 intervention arms.

Analysis: Intention to treat, adjusting for within-household correlation in influenza attack rates.

Eligibility criteria: Inclusion Criteria:

* All vaccinees must be Hong Kong residents aged between 6 and 17.

Exclusion Criteria:

* Vaccinees should not be allergic or hypersensitive to the active substances or components (eggs, chicken proteins, formaldehyde, neomycin, etc.) used in the vaccines or where vaccination is otherwise contraindicated. Subjects should not have an underlying immunocompromised condition or be receiving immunosuppressive agents.

Primary outcomes:
measure: The proportions of subjects and household contacts with serology-confirmed influenza infection during follow-up among the 2 intervention arms.
timeFrame: nine months
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: The University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Benjamin J Cowling, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cowling BJ, Ng S, Ma ES, Fang VJ, So HC, Wai W, Cheng CK, Wong JY, Chan KH, Ip DK, Chiu SS, Peiris JS, Leung GM. Protective efficacy against pandemic influenza of seasonal influenza vaccination in children in Hong Kong: a randomized controlled trial. Clin Infect Dis. 2012 Sep;55(5):695-702. doi: 10.1093/cid/cis518. Epub 2012 Jun 5.
citation: Cowling BJ, Ng S, Ma ES, Cheng CK, Wai W, Fang VJ, Chan KH, Ip DK, Chiu SS, Peiris JS, Leung GM. Protective efficacy of seasonal influenza vaccination against seasonal and pandemic influenza virus infection during 2009 in Hong Kong. Clin Infect Dis. 2010 Dec 15;51(12):1370-9. doi: 10.1086/657311. Epub 2010 Nov 10.
citation: Cowling BJ, Perera RA, Fang VJ, Chan KH, Wai W, So HC, Chu DK, Wong JY, Shiu EY, Ng S, Ip DK, Peiris JS, Leung GM. Incidence of influenza virus infections in children in Hong Kong in a 3-year randomized placebo-controlled vaccine study, 2009-2012. Clin Infect Dis. 2014 Aug 15;59(4):517-24. doi: 10.1093/cid/ciu356. Epub 2014 May 13.