Influenza
Conditions
Keywords
influenza vaccine, adult, immunogenicity, reactogenicity
Brief summary
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
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.
Interventions
BIOLOGICALFluzone High-Dose
Influenza vaccine
BIOLOGICALFluzone (standard dose)
Influenza vaccine
Sponsors
Mount Sinai Hospital, Canada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. 18-64 years old, inclusive, as of October 1st of year of enrolment; 2. Healthcare worker, broadly defined as a person either providing health care, or working in an acute care hospital or long term healthcare facility; 3. 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; 4. Understand the study, agree to its requirements, and give written consent;
Exclusion criteria
1. Receipt of influenza vaccine for the current northern hemisphere season prior to randomization; 2. Serious adverse event to a previous dose of influenza vaccine; 3. Immunoglobulin E mediated allergic reaction to a previous dose of influenza vaccine or to any excipients in the study vaccines 4. Previous episode of Guillain-Barré syndrome with 6 weeks of receiving an influenza vaccine; 5. Receipt of immunoglobulins, blood or blood-derived products in the past 3 months; 6. 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 7. Plans to receive any vaccine, initiate any medication, or be admitted to hospital before day 21 after vaccination (visit 2); 8. 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) 9. 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; 10. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seroconversion to A/California/07/2009 (H1N1) | 21 days (18-28) | Seroconversion to influenza strains contained in the vaccine, as measured by hemagglutination inhibition (HAI) assay. 4-fold or greater increase. |
| Number of Participants With Seroconversion to A/Texas/50/2012 (H3N2) | 21 days post vaccination (18-28) | Four-fold or higher rise in titres to A/Texas/50/2012 (H3N2) as measured by hemagglutination inhibition assay |
| Number of Participants With Seroconversion to Influenza B/Phuket/3073/2013 | 21 days post-vaccination (18-28) | Four fold or higher increase in titres to B/Phuket/3073/2013 as measured by hemagglutination inhibition assay |
| Number of Participants With Seroconversion to A/Switzerland/9715293/2013 (H3N2) | 21 days post vaccination (18-28) | Four-fold or higher rise in titres against A/Switzerland/9715293/2013 (H3N2) as measured by hemagglutination inhibition assay |
| Number of Participants With Seroconversion to B/Massachusetts/02/2012 | 21 days post-vaccination (18-28) | Four fold or higher increase in titres to B/Massachusetts/02/2012 as measured by hemagglutination inhibition assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Fold Ratio (GMFR): B/Massachusetts/02/2012 Ether-treated | 21 days (18-28) | GMFR (mean fold increase) time2/time1, as measured by HAI titres |
| Number of Participants Reporting Adverse Event: Injection Site | 7 days | Any local adverse event following immunization,self reported in daily diary Includes the maximum values for any one of: redness, warmth, swelling, or bruising |
| Number of Participants Reporting Adverse Event: Systemic | 7 days | 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 |
| Geometric Mean Fold Ratio (GMFR) Against A/California/07/2009 (H1N1) | 21 days (18-28) | GMFR (mean fold increase) time2/time1, as measured by hemagglutination inhibition assay |
| Geometric Mean Fold Ratio (GMFR): A/Switzerland/9715293/2013 | 21 days (18-28) | GMFR (mean fold increase) time2/time1, as measured by HAI titres |
| Geometric Mean Fold Ratio (GMFR): A/Texas/50/2012 | 21 days (18-28) | GMFR (mean fold increase) time2/time1, as measured by HAI titres |
| Geometric Mean Fold Ratio (GMFR): B/Phuket/3073/2013 Ether-treated | 21 days (18-28) | GMFR (mean fold increase) time2/time1, as measured by HAI titres |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose Fluzone Fluzone High-Dose® Licensed for use in the USA in persons ≥ 65 years of age as a single dose of 0.5mL containing 60μg HA per virus strain
Fluzone High-Dose: Influenza vaccine | 87 |
| Fluzone (Standard Dose) Fluzone ® Licensed for the prevention of influenza as a single dose of 0.5mL containing 15μg HA per virus strain for adults
Fluzone (standard dose): Influenza vaccine | 83 |
| Total | 170 |
Baseline characteristics
| Characteristic | High Dose Fluzone | Total | Fluzone (Standard Dose) |
|---|---|---|---|
| Age, Continuous | 46 years | 47.5 years | 50 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 87 participants | 170 participants | 83 participants |
| Sex: Female, Male Female | 64 Participants | 123 Participants | 59 Participants |
| Sex: Female, Male Male | 23 Participants | 47 Participants | 24 Participants |
| Underlying chronic medical condition | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 83 |
| other Total, other adverse events | 26 / 87 | 6 / 83 |
| serious Total, serious adverse events | 0 / 87 | 0 / 83 |
Outcome results
Primary
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.
Time frame: 21 days (18-28)
Population: A blood sample from one participant was hemolysed and not available for analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Fluzone | Number of Participants With Seroconversion to A/California/07/2009 (H1N1) | 41 Participants |
| Fluzone (Standard Dose) | Number of Participants With Seroconversion to A/California/07/2009 (H1N1) | 21 Participants |
Primary
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
Time frame: 21 days post vaccination (18-28)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Fluzone | Number of Participants With Seroconversion to A/Switzerland/9715293/2013 (H3N2) | 58 Participants |
| Fluzone (Standard Dose) | Number of Participants With Seroconversion to A/Switzerland/9715293/2013 (H3N2) | 49 Participants |
Primary
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
Time frame: 21 days post vaccination (18-28)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Fluzone | Number of Participants With Seroconversion to A/Texas/50/2012 (H3N2) | 17 Participants |
| Fluzone (Standard Dose) | Number of Participants With Seroconversion to A/Texas/50/2012 (H3N2) | 4 Participants |
Primary
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
Time frame: 21 days post-vaccination (18-28)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Fluzone | Number of Participants With Seroconversion to B/Massachusetts/02/2012 | 8 Participants |
| Fluzone (Standard Dose) | Number of Participants With Seroconversion to B/Massachusetts/02/2012 | 3 Participants |
Primary
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
Time frame: 21 days post-vaccination (18-28)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Fluzone | Number of Participants With Seroconversion to Influenza B/Phuket/3073/2013 | 29 Participants |
| Fluzone (Standard Dose) | Number of Participants With Seroconversion to Influenza B/Phuket/3073/2013 | 12 Participants |
Secondary
Geometric Mean Fold Ratio (GMFR) Against A/California/07/2009 (H1N1)
GMFR (mean fold increase) time2/time1, as measured by hemagglutination inhibition assay
Time frame: 21 days (18-28)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose Fluzone | Geometric Mean Fold Ratio (GMFR) Against A/California/07/2009 (H1N1) | 1.38 fold ratio |
| Fluzone (Standard Dose) | Geometric Mean Fold Ratio (GMFR) Against A/California/07/2009 (H1N1) | 1.20 fold ratio |
Secondary
Geometric Mean Fold Ratio (GMFR): A/Switzerland/9715293/2013
GMFR (mean fold increase) time2/time1, as measured by HAI titres
Time frame: 21 days (18-28)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose Fluzone | Geometric Mean Fold Ratio (GMFR): A/Switzerland/9715293/2013 | 1.82 fold ratio |
| Fluzone (Standard Dose) | Geometric Mean Fold Ratio (GMFR): A/Switzerland/9715293/2013 | 1.67 fold ratio |
Secondary
Geometric Mean Fold Ratio (GMFR): A/Texas/50/2012
GMFR (mean fold increase) time2/time1, as measured by HAI titres
Time frame: 21 days (18-28)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose Fluzone | Geometric Mean Fold Ratio (GMFR): A/Texas/50/2012 | 1.76 fold ratio |
| Fluzone (Standard Dose) | Geometric Mean Fold Ratio (GMFR): A/Texas/50/2012 | 1.15 fold ratio |
Secondary
Geometric Mean Fold Ratio (GMFR): B/Massachusetts/02/2012 Ether-treated
GMFR (mean fold increase) time2/time1, as measured by HAI titres
Time frame: 21 days (18-28)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose Fluzone | Geometric Mean Fold Ratio (GMFR): B/Massachusetts/02/2012 Ether-treated | 1.20 fold ratio |
| Fluzone (Standard Dose) | Geometric Mean Fold Ratio (GMFR): B/Massachusetts/02/2012 Ether-treated | 1.08 fold ratio |
Secondary
Geometric Mean Fold Ratio (GMFR): B/Phuket/3073/2013 Ether-treated
GMFR (mean fold increase) time2/time1, as measured by HAI titres
Time frame: 21 days (18-28)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose Fluzone | Geometric Mean Fold Ratio (GMFR): B/Phuket/3073/2013 Ether-treated | 1.32 fold ratio |
| Fluzone (Standard Dose) | Geometric Mean Fold Ratio (GMFR): B/Phuket/3073/2013 Ether-treated | 1.19 fold ratio |
Secondary
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
Time frame: 7 days
Population: All participants were able to provide data
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Injection Site | none | 47 Participants |
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Injection Site | mild | 34 Participants |
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Injection Site | moderate | 6 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Injection Site | none | 62 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Injection Site | mild | 21 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Injection Site | moderate | 0 Participants |
Secondary
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
Time frame: 7 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Systemic | None | 41 Participants |
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Systemic | Mild | 23 Participants |
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Systemic | Moderate | 18 Participants |
| High Dose Fluzone | Number of Participants Reporting Adverse Event: Systemic | Extreme | 5 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Systemic | Extreme | 3 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Systemic | None | 42 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Systemic | Moderate | 13 Participants |
| Fluzone (Standard Dose) | Number of Participants Reporting Adverse Event: Systemic | Mild | 25 Participants |