A Pilot Study to Assess the Immunogenicity and Reactogenicity of High Versus Standard Dose TIV

Study Overview
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Brief Summary
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The objective of this pilot study is to assess the immunogenicity and reactogenicity of Fluzone High Dose with Fluzone (standard adult dose) influenza vaccines in healthcare workers.

Detailed Description
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This is a prospective, randomized controlled, observer blind trial of Fluzone High Dose trivalent inactivated influenza vaccine (HDTIV) versus Fluzone, standard dose TIV (SDTIV) in 100 healthcare workers 18-64 years of age. Participants will receive, in a 1:1 ratio, one dose of either SDTIV or HDTIV containing the strains of influenza virus as recommended by the World Health Organization for the season of recruitment. All adverse events will be collected for 7 days following the injection, serious adverse events will be collected through day 21, and serum for antibody testing will be obtained on day 0 and day 21. The primary outcome will be seroconversion to each strain of vaccine included in the vaccine, as measured by change in hemagglutination inhibition assay (HAI) titer between day 0 to day 21.

Official Title
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A Pilot Study to Assess the Immunogenicity and Reactogenicity of High Versus Standard Dose Trivalent Inactivated Influenza Vaccine for Healthcare Workers

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluzone High-Dose
* Biological: Fluzone (standard dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-64 years old, inclusive, as of October 1st of year of enrolment; Healthcare worker, broadly defined as a person either providing health care, or working in an acute care hospital or long term healthcare facility; Has access to email and the internet for adverse event reporting, or is willing to complete forms on paper and deliver to the site study office; Understand the study, agree to its requirements, and give written consent; Exclusion Criteria: Receipt of influenza vaccine for the current northern hemisphere season prior to randomization; Serious adverse event to a previous dose of influenza vaccine; Immunoglobulin E mediated allergic reaction to a previous dose of influenza vaccine or to any excipients in the study vaccines Previous episode of Guillain-Barré syndrome with 6 weeks of receiving an influenza vaccine; Receipt of immunoglobulins, blood or blood-derived products in the past 3 months; Receipt of another vaccine, or initiation of new medication, or hospital admission for any reason within the 30 days prior to the study dose of vaccine Plans to receive any vaccine, initiate any medication, or be admitted to hospital before day 21 after vaccination (visit 2); Known or suspected congenital or acquired immunodeficiency (including HIV infection); or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Any condition, including but not limited to drug and alcohol addiction, which, in the opinion of the investigator might interfere with the ability to comply with trial conduct or completion; Moderate or severe acute illness or active infection or fever (temperature ≥37.8oC) on the day the vaccine dose is due (participant may receive dose of vaccine 48 hours after symptoms have resolved and body temperature has returned to normal without the use of antipyretics.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose Fluzone<br>Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5 mL containing 60μg hemagglutinin per virus strain | Biological: Fluzone High-Dose<br>* Influenza vaccine<br>|
| Active Comparator: Fluzone (standard dose)<br>Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5 mL containing 15μg hemagglutinin per virus strain for adults | Biological: Fluzone (standard dose)<br>* Influenza vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroconversion to A/California/07/2009 (H1N1) | Seroconversion to influenza strains contained in the vaccine, as measured by hemagglutination inhibition (HAI) assay. 4-fold or greater increase. | 21 days (18-28) | 
| Number of Participants With Seroconversion to A/Texas/50/2012 (H3N2) | Four-fold or higher rise in titres to A/Texas/50/2012 (H3N2) as measured by hemagglutination inhibition assay | 21 days post vaccination (18-28) | 
| Number of Participants With Seroconversion to Influenza B/Phuket/3073/2013 | Four fold or higher increase in titres to B/Phuket/3073/2013 as measured by hemagglutination inhibition assay | 21 days post-vaccination (18-28) | 
| Number of Participants With Seroconversion to A/Switzerland/9715293/2013 (H3N2) | Four-fold or higher rise in titres against A/Switzerland/9715293/2013 (H3N2) as measured by hemagglutination inhibition assay | 21 days post vaccination (18-28) | 
| Number of Participants With Seroconversion to B/Massachusetts/02/2012 | Four fold or higher increase in titres to B/Massachusetts/02/2012 as measured by hemagglutination inhibition assay | 21 days post-vaccination (18-28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Ratio (GMFR) Against A/California/07/2009 (H1N1) | GMFR (mean fold increase) time2/time1, as measured by hemagglutination inhibition assay | 21 days (18-28) | 
| Geometric Mean Fold Ratio (GMFR): A/Switzerland/9715293/2013 | GMFR (mean fold increase) time2/time1, as measured by HAI titres | 21 days (18-28) | 
| Geometric Mean Fold Ratio (GMFR): A/Texas/50/2012 | GMFR (mean fold increase) time2/time1, as measured by HAI titres | 21 days (18-28) | 
| Geometric Mean Fold Ratio (GMFR): B/Phuket/3073/2013 Ether-treated | GMFR (mean fold increase) time2/time1, as measured by HAI titres | 21 days (18-28) | 
| Geometric Mean Fold Ratio (GMFR): B/Massachusetts/02/2012 Ether-treated | GMFR (mean fold increase) time2/time1, as measured by HAI titres | 21 days (18-28) | 
| Number of Participants Reporting Adverse Event: Injection Site | Any local adverse event following immunization,self reported in daily diary Includes the maximum values for any one of: redness, warmth, swelling, or bruising | 7 days | 
| Number of Participants Reporting Adverse Event: Systemic | Any systemic adverse event following immunization,self reported in daily diary Includes the maximum value reported for any one of: myalgia, arthralgia, headache, malaise, fatigue, weakness, sweating, shivering, or feverishness Defined as: None: Not at all Mild: Present, but did not interfere with activities Moderate: Interfered with activities, but didn't prevent them Extreme: Prevented activities | 7 days | 

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