Direct and Indirect Benefits of Influenza Vaccine Versus Placebo in Healthy Children

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomised Controlled Trial of the Effectiveness of Vaccinating Children to Reduce Household Transmission of Influenza

Conditions
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Influenza Virus Infection

Intervention / Treatment
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* Biological: Inactivated influenza vaccine
* Biological: Saline


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Influenza vaccine | Biological: Inactivated influenza vaccine<br>* 0.5ml intramuscular single dose<br>* Other names: VAXIGRIP®, Sanofi Pasteur;|
| Placebo Comparator: 2<br> | Biological: Saline<br>* 0.5ml intramuscular, one dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportions of subjects and household contacts with serology-confirmed influenza infection during follow-up among the 2 intervention arms. |  | nine months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, vaccination, children, Influenza-like illness