Hutterite Influenza Prevention Study

Does Vaccinating Health Hutterite Children Against Influenza Prevent Influenza in Other Hutterite Colony Members: A Randomized Cluster Trial

The goal of this randomized clinical trial is to determine whether immunizing children in Hutterite colonies with inactivated influenza vaccine can prevent influenza and its complications in other colony members. Furthermore, the study will assess the indirect benefit to Hutterites at high risk of complications. The study is a blinded, cluster randomized controlled trial among Hutterite colonies to test the hypothesis that high immunization rates (>70%) of healthy children with inactivated influenza vaccine reduces transmission of influenza to other colony members. Randomization of these homogeneous, moderately sized colonies where there is regular spread facilitated by a communal lifestyle, but limited re-introduction because of relative isolation from outside community, represents a unique opportunity to test the hypothesis of indirect benefit under close to ideal conditions. The primary outcome will be laboratory-confirmed influenza. Secondary outcomes include influenza-like illness, otitis media, physician visits, antimicrobial prescriptions, absenteeism, lower respiratory tract infection, hospitalizations, and death.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Influenza vaccination; Biological: Hepatitis A Vaccine

Detailed Description

Colonies will be enrolled in September 2008.

Healthy Hutterite Children will be vaccinated in October, in each year of the study (2008, 2009, & 2010)

Influenza Surveillance phase will begin around December-January of each year.

• All study outcomes will be collected during the Surveillance phase of the study from Dec to June for 3 years.
• Outcomes will be collected when research nurses visit the colonies. A research nurse will visit enrolled colonies twice a week during the surveillance phase and review study diaries and obtain swabs from participants with symptoms of influenza.

• Study Type: Interventional
• Enrollment (Actual): 4771
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Group A:

Inclusion Criteria:

• Hutterites other than the healthy children who will be immunized. Although this category as a whole will be used to assess indirect benefit of the vaccine in the main analysis, Hutterites at high risk for influenza complications within this category will be assessed in a separate analysis. These are defined as anyone in one or more of the following groups:
• individuals aged ≥ 65 years
• children 23 months of age or less

• anyone with ≥ 1 of the following conditions severe enough to require regular medical follow-up or hospital care:

  • chronic cardiac or pulmonary disorders (including bronchopulmonary dysplasia, cystic fibrosis, and asthma)
  • diabetes mellitus and other metabolic diseases
  • cancer
  • immunodeficiency
  • immunosuppression (due to underlying disease and/or therapy)
  • renal disease
  • anemia
  • hemoglobinopathy
  • any condition that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk of aspiration.

Exclusion Criteria:

• There are no exclusion criteria for this category of participants.

Group B:

Inclusion Criteria:

• Healthy children aged 36 months to 15 years who will be immunized as part of the intervention.

Exclusion Criteria:

• Anaphylactic reaction to a previous dose of influenza vaccine
• Anaphylactic reaction to hepatitis A vaccine
• Anaphylactic reaction to neomycin
• Known IgE-mediated hypersensitivity to eggs manifested as hives
• Swelling of the mouth and throat, difficulty in breathing, hypotension, or shock
• Guillain-Barré syndrome within eight weeks of a previous influenza vaccine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Influenza; Inactivated Influenza vaccination	Biological: Influenza vaccination; Influenza vaccination- 0.5 mL. Children under 9 who have never received a influenza vaccine will receive a 2nd dose (0.5 mL) 4 weeks later.; Other Names: Vaxigrip by Sanofi Pasteur
Placebo Comparator: Control; Hepatitis A vaccine	Biological: Hepatitis A Vaccine; Hepatitis vaccination- 0.5 mL. Children under 9 who have never received a influenza vaccine will receive a 2nd dose ( saline- 0.5 mL) 4 weeks later.; Other Names: Avaxim Pediatric by Sanofi Pasteur

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
laboratory-confirmed influenza infection	Dec to June each year for 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Influenza like illness	Dec to June each year for 3 years
Physician diagnosed otitis media	Dec to June each year for 3 years
School or work related absenteeism	Dec to June each year for 3 years
Physician visits for respiratory illness	Dec to June each year for 3 years
Lower respiratory infection or pneumonia	Dec to June each year for 3 years
Hospitalizations for LRTI or pneumonia	Dec to June each year for 3 years
All cause hospitalizations	Dec to June each year for 3 years
Deaths due to LRTI or pneumonia	Dec to June each year for 3 years
All-cause deaths	Dec to June each year for 3 years

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Mark B Loeb, MD, McMaster University

Publications and helpful links

General Publications

• Wang B, Russell ML, Moss L, Fonseca K, Earn DJ, Aoki F, Horsman G, Caeseele PV, Chokani K, Vooght M, Babiuk L, Webby R, Walter SD, Loeb M. Effect of Influenza Vaccination of Children on Infection Rate in Hutterite Communities: Follow-Up Study of a Randomized Trial. PLoS One. 2016 Dec 15;11(12):e0167281. doi: 10.1371/journal.pone.0167281. eCollection 2016.
• Loeb M, Russell ML, Fonseca K, Webby R, Walter SD. Comparison of multiple estimates of efficacy for influenza vaccine. Vaccine. 2011 Dec 9;30(1):1-4. doi: 10.1016/j.vaccine.2011.10.069. Epub 2011 Nov 7.
• Loeb M, Russell ML, Moss L, Fonseca K, Fox J, Earn DJ, Aoki F, Horsman G, Van Caeseele P, Chokani K, Vooght M, Babiuk L, Webby R, Walter SD. Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. JAMA. 2010 Mar 10;303(10):943-50. doi: 10.1001/jama.2010.250.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: January 22, 2009
• First Submitted That Met QC Criteria: April 6, 2009
• First Posted (Estimate): April 7, 2009

Study Record Updates

• Last Update Posted (Estimate): September 28, 2011
• Last Update Submitted That Met QC Criteria: September 27, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: MCT 88113