Influenza
Conditions
Keywords
influenza, vaccine, observer blind
Brief summary
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.
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.
Interventions
BIOLOGICALFluviral influenza vaccine, 2009-2010
0.5 mL intramuscular
BIOLOGICALNormal saline
0.5 mL intramuscular
Sponsors
GlaxoSmithKline
Mount Sinai Hospital, Canada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of pH1N1 Influenza Infections as Diagnosed by PCR From Mid-turbinate Swab | day +7 post seasonal influenza vaccination (or placebo) to end of study | 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) |
Countries
Canada
Participant flow
Recruitment details
Enrolment start: October 5, 2009 Enrolment complete: February 3, 2010 Enrolment was conducted from a variety of work places and university settings.
Participants by arm
| Arm | Count |
|---|---|
| Seasonal Influenza Vaccination Receipt of Fluviral seasonal (2009-2010, Canadian) influenza vaccination as per manufacturers specification | 234 |
| Placebo 0.5 mL normal saline | 234 |
| Total | 468 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 16 | 10 |
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Seasonal Influenza Vaccination | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 234 Participants | 233 Participants | 467 Participants |
| Age Continuous | 35.7 years STANDARD_DEVIATION 12.5 | 36.8 years STANDARD_DEVIATION 12.6 | 36.3 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment Canada | 234 participants | 234 participants | 468 participants |
| Sex: Female, Male Female | 157 Participants | 148 Participants | 305 Participants |
| Sex: Female, Male Male | 77 Participants | 86 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 234 | 0 / 234 |
| serious Total, serious adverse events | 1 / 234 | 1 / 234 |
Outcome results
Primary
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)
Time frame: day +7 post seasonal influenza vaccination (or placebo) to end of study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Seasonal Influenza Vaccination | Number of pH1N1 Influenza Infections as Diagnosed by PCR From Mid-turbinate Swab | 2 participants |
| Placebo | Number of pH1N1 Influenza Infections as Diagnosed by PCR From Mid-turbinate Swab | 4 participants |
Comparison: Null hypothesis: There is no difference in incidence of pandemic strain influenza infection for people given seasonal influenza vaccine compared to those given a placebo.~Power to detect a 2-fold difference if attack rate in non-vaccinated participants is 10%: 86%p-value: 0.685Fisher Exact