Do Some Healthy Adults Consistently Have Systemic Reactions to Influenza Vaccines?

Study Overview
=================
Brief Summary
-----------------
This study will recruit 35 healthcare workers who had systemic reactions to influenza vaccine the last 2 times they were vaccinated, to ask whether influenza vaccine is indeed associated with systemic reactions in these workers.

Detailed Description
-----------------
Randomized controlled trials of split virus vaccines in healthy adults have not been able to detect an increase in systemic adverse events compared to control vaccination. These trials do identify a non-trivial risk of systemic symptoms occurring in the week after both placebo and vaccine. There is a small population of healthcare workers who report consistent systemic symptoms after split virus vaccination which may occur because a small group of healthy adults have true physical reactions to components of the vaccine or excipients. If this is true, then alternatives - such as the use of subunit vaccines or live attenuated nasal spray vaccines - might be expected to be better tolerated by these people.

Official Title
-----------------
Do Some Healthy Adults Consistently Have Systemic Reactions to Trivalent Inactivated Split Virus Influenza Vaccines?

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Employed or volunteer in a healthcare facility or an ambulatory care setting providing healthcare By self report, have had 2 or more doses of trivalent inactivated influenza vaccine (TIIV) in the last 15 years, and after at least the last 2 vaccine doses have had the same systemic adverse event in the 7 days after vaccination, including: fever, chills, myalgia, arthralgia, fatigue, headache, or insomnia; Consent to the study, including two injections one month apart, with one being placebo and one a dose of TIIV; Exclusion Criteria: Has a contraindication to TIIV (previous allergic reaction to a dose of vaccine, or Guillain Barre syndrome with onset within 6 weeks of vaccination); Has previously received a dose of TIIV for the current influenza season. Receipt of another vaccine, or initiation of new medication within 7 days of the study injection (participant may enter the study as long as the gap between other vaccine/initiation of new medication is >7 days); Moderate or severe acute illness or active infection or fever (temperature ≥37.8oC) on the day a dose of study medication due (participant may receive injection 48 hours after symptoms have resolved and body temperature has returned to normal without the use of antipyretics.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine, then placebo<br>1 injection of trivalent inactivated influenza vaccine, 0.5mL/dose, as approved for use in Canada for season of enrolment followed by 1 injection of normal saline placebo, 0.5mL/dose, 28 days later | Biological: Vaccine<br>* Licensed trivalent inactivated influenza vaccine<br>* Other names: Trivalent inactivated influenza vaccine;|
| Experimental: Placebo, then vaccine<br>1 injection of normal saline placebo, 0.5mL/dose followed by 1 injection of trivalent inactivated influenza vaccine, 0.5mL/dose, as approved for use in Canada for season of enrolment, 28 days later | Biological: Vaccine<br>* Licensed trivalent inactivated influenza vaccine<br>* Other names: Trivalent inactivated influenza vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic adverse event | Any systemic adverse event, self-reported | 7 days after each injection | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
influenza vaccine, adult, safety, reactogenicity