Does Seasonal Influenza Vaccination Affect the Incidence of pH1N1 Influenza?

A Randomized Controlled Trial of the Effect of Seasonal Influenza Vaccination on the Incidence of Infection Due to the 2009 H1N1 Influenza

Since the onset of the 2009 pandemic, several observational public health investigations in Canada have identified evidence that suggests that adults, particularly younger adults, who have previously received seasonal influenza vaccine are at increased risk of infection with the 2009 pandemic strain of H1N1 (pH1N1). Investigations in Australia, the United States and the United Kingdom have not identified this effect. While it is not possible to have an answer to whether this affect is real prior to the second wave of the 2009 pandemic, it remains vital to future influenza vaccination programs that the hypothesis that, in 2009, seasonal vaccine increases or decreases the risk of pH1N1 infection be confirmed or refuted.

The objective of this study is to determine whether Ontario adults aged 18-60 years who receive the 2009 seasonal influenza vaccine will be at a 2 fold or greater increased risk of infection with influenza pH1N1 during the second or third wave of the 2009 pandemic.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluviral influenza vaccine, 2009-2010; Biological: Normal saline

Detailed Description

This study will be an observer -blind randomized controlled trial.

This study will primarily recruit patients from an existing cohort of adult health care and other workers in Toronto, as of September 15, 2009, almost 1000 adults are participating in this cohort; with approximately 75 new cohort members being recruited weekly (target is 1300). Recruitment will be supplemented by enrollment at Hamilton Health Sciences Centre (N~3920 employees plus physicians & midwives) and Queen Elizabeth II Health Centre in Halifax (N~6000 employees plus physicians & midwives).

To date, health care workers in the Toronto cohort have been recruited at the Mount Sinai Hospital, Toronto East General Hospital, and North York General Hospital. Recruitment is just beginning at Sunnybrook Health Sciences Centre, and the University Health Network.

Non-health care workers are being recruited from several large Toronto employers of primarily office workers. These include the Ontario Agency for Health Protection and Promotion, the head offices of the Ontario Power Generation Corporation, the Art Gallery of Ontario, and the head offices of Scotia Bank. Non-health care workers should meet inclusion criteria and should not work primarily with children or from a home office.

Participants in the study are completing web-based diaries weekly, and, whenever they develop symptoms possibly compatible with influenza, are submitting nasal swabs, and completing symptom diaries daily while ill. Nasal swabs are tested by polymerase chain reaction (PCR) on a same or next day basis with antivirals prescribed to participants who develop influenza.

• Study Type: Interventional
• Enrollment (Actual): 468
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • North York, Ontario, Canada, M2K 1E1
      • North York General Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 60 years old, inclusive, as of September 1st, 2009;
2. understand the study, agree to its provisions, and give written informed consent prior to entry;
3. available for follow-up during the study period;
4. have convenient access to a computer with internet access and basic skills for use of the internet;

Exclusion Criteria:

1. planning to spend more than two consecutive weeks outside of Canada from October 1, 2009 to April 15th 2010.
2. received immunoglobulin within six months of study entry;
3. has already received a 2009 seasonal influenza vaccine (southern or northern hemisphere)
4. has had laboratory-confirmed infection with 2009 H1N1 influenza
5. is participating in a clinical trial that would result in the receipt of investigational medication during the study period;
6. allergic to eggs, to influenza vaccine, or any components of the seasonal influenza vaccine
7. has had a previous severe adverse event associated with an influenza vaccine
8. has a significant chronic underlying illness that would warrant seasonal influenza vaccine in a usual year, or is known to be pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Seasonal influenza vaccination; Receipt of Fluviral seasonal (2009-2010, Canadian) influenza vaccination as per manufacturers specification	Biological: Fluviral influenza vaccine, 2009-2010; 0.5 mL intramuscular
Placebo Comparator: Placebo; 0.5 mL normal saline	Biological: Normal saline; 0.5 mL intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of pH1N1 Influenza Infections as Diagnosed by PCR From Mid-turbinate Swab	Influenza infection (pH1N1) as diagnosed by PCR from self-collected mid-turbinate swab. Participant is asked to collect a swab when they have symptoms possibly compatible with an acute viral respiratory illness: 1) fever without another obvious source, 2) at least two new respiratory symptoms (runny or stuffy nose, sneezing, sore or scratchy throat, hoarseness, cough), or 3) one respiratory symptom (as above) and one systemic symptom (fever, malaise, muscle aches, headache, fatigue)	day +7 post seasonal influenza vaccination (or placebo) to end of study

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Brenda L. Coleman, PhD, Mount Sinai Hospital; Principal Investigator: Natasha Crowcroft, MD, Ontario Agency for Health Protection & Promotion; Study Director: Karen Green, MSc, Mount Sinai Hospital; Study Director: Kevin Katz, MD, North York General Hospital; Study Director: Mark Loeb, MD, Hamilton Health Sciences Centre; Study Director: Donald Low, MD, Mount Sinai Hospital; Study Director: Shelly McNeil, MD, Queen Elizabeth II Health Sciences Centre; Study Director: Matthew Muller, MD, PhD, Unity Health Toronto; Study Director: Andrew Simor, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: October 23, 2009
• First Submitted That Met QC Criteria: October 23, 2009
• First Posted (Estimate): October 26, 2009

Study Record Updates

• Last Update Posted (Estimate): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 18, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: vaccine; influenza; observer blind
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: CRT113936 (Other Grant/Funding Number: GSK)