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FLUAD® vs. Fluzone® High-Dose Study

Sponsor
Duke University (Other)
Overall Status
Completed
CT.gov ID
NCT03183908
Collaborator
Centers for Disease Control and Prevention (U.S. Fed), Boston Medical Center (Other), Children's Hospital Medical Center, Cincinnati (Other)
757
Enrollment
4
Locations
2
Arms
17.6
Actual Duration (Months)
189.3
Patients Per Site
10.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall aim of the study is to compare safety and immunogenicity of inactivated influenza vaccine (IIV), adjuvanted (FLUAD®) versus High-Dose inactivated influenza (Fluzone® High-Dose) vaccine in persons ≥65 years (20% aged ≥80 years). A prospective, randomized, blinded clinical trial that will be conducted during the 2017/2018 and 2018/2019 influenza seasons. During each season, approximately 220 older adults will be enrolled at Duke University Medical Center and 140 older adults at Boston University Medical Center. Eligible subjects will be randomized to receive either adjuvanted influenza vaccine or High-Dose influenza vaccine. All subjects will receive vaccine and provide a blood draw at Visit 1, and then return for a second blood draw without vaccination about 4 weeks later to assess for influenza antibody titers. A subset of 100 subjects at Duke will provide a third blood draw 6 months post-vaccination to assess for waning of influenza antibody titers. Subjects will record the occurrence of local and systemic reactions (including fever, pain, tenderness, swelling, redness, general systemic systems), unsolicited adverse events, medical care utilization, and changes in medications over 8 days following vaccination. In addition, serious adverse events and events of clinical interest will be assessed through 42 days post-vaccination. Health-related quality of life will be assessed pre-vaccination (Day 1) and on Days 3 and 9 post-vaccination.

Condition or Disease Intervention/Treatment Phase
  • Biological: FLUAD®
  • Biological: Fluzone® High-Dose
 Phase 4

Detailed Description

Full Analysis Population 1: Defined as all subjects who are randomized, vaccinated, and provide at least one day of complete data on the symptom diary.

Full Analysis Population 2: Defined as all subjects who are randomized and vaccinated.

Immunogenicity Population: Defined as subjects who received vaccine, provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Study Design

Study Type:
Interventional
Actual Enrollment :
757 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Subject, study coordinators, and investigators will be blinded to the type of flu vaccine administered. Only the vaccinator will be unblinded.
Primary Purpose:
Prevention
Official Title:
Safety and Immunogenicity of Adjuvanted Versus High-Dose Inactivated Influenza Vaccines in Older Adults
Actual Study Start Date :
Aug 28, 2017
Actual Primary Completion Date :
Feb 14, 2019
Actual Study Completion Date :
Feb 14, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Adjuvanted influenza vaccine (FLUAD®)

In the study arm, subjects will receive a single dose of FLUAD® adjuvanted influenza vaccine during Visit 1.

Biological: FLUAD®
Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Other Names:
  • Adjuvanted influenza vaccine

    		•
    Active Comparator: High-dose influenza vaccine (Fluzone® HD)

    In the study arm, subjects will receive a single dose of Fluzone® High-Dose influenza vaccine during Visit 1.

    Biological: Fluzone® High-Dose
    Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Other Names:
  • High-dose influenza vaccine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Injection-Site Pain in Arm That Was Vaccinated, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of the proportion of subjects reporting moderate/severe injection site pain within the first week post-vaccination in both treatment groups.

    2. Number of Participants With Adverse Events of Clinical Interest, Population 2 [42 days post-vaccination and compared between the two groups.]

      The frequency and descriptions of adverse events of clinical interest observed in the two treatment groups.

    3. Observed Serious Adverse Events in Both Treatment Groups, Population 2 [42 days post-vaccination and compared between the two groups.]

      The frequency and descriptions of serious adverse events observed in the two treatment groups. No analytical analysis was completed.

    4. Number of Participants With H3N2 HAI Seroconversion [29 days post-vaccination]

      H3N2 hemagglutination inhibition assay (HAI) seroconversion: The proportion of subjects achieving H3N2 seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer is > 1:10) in the respective season's vaccine

    Secondary Outcome Measures

    1. Number of Participants With Local Reactions in Arm That Was Vaccinated - Full Study, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of local reactions within the first week post-vaccination in both treatment groups.

    2. Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 65 - 79, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of local reactions within the first week post-vaccination in both treatment groups by age group.

    3. Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 80 +, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of local reactions within the first week post-vaccination in both treatment groups by age group.

    4. Number of Participants With Systemic Reactions - Full Study Population, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of systemic reactions within the first week post-vaccination in both treatment groups.

    5. Number of Participants With System Reactions - Ages 65 - 79, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of systemic reactions within the first week post-vaccination in both treatment groups by age group.

    6. Number of Participants With System Reactions - Ages 80 +, Population 1 [Days 1 through 8 post-vaccination]

      Comparison of systemic reactions within the first week post-vaccination in both treatment groups by age group.

    7. Quality of Life - Late Life Function & Disability Instrument - Full Population [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).

    8. Quality of Life - Late Life Function & Disability Instrument - Ages 65 - 79 [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).

    9. Quality of Life - Late Life Function & Disability Instrument - Ages 80 + [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).

    10. Quality of Life - EQ-5D-5L -Full Population [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups (Year 1 only). Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).

    11. Quality of Life - EQ-5D-5L - Ages 65 - 79 [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).

    12. Quality of Life - EQ-5D-5L - Ages 80 + [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only) Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).

    13. Quality of Life - EQ VAS -Full Population [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).

    14. Quality of Life - EQ VAS - Ages 65 - 79 [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).

    15. Quality of Life - EQ VAS - Ages 80 + [Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)]

      Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).

    16. Seroconversion - 65 and Older [Day 29 (28 days post-vaccination)]

      The proportion of subjects achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer

    17. Seroprotection - 65 and Older [Day 29 (28 days post-vaccination)]

      Proportion of subjects with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine

    18. Geometric Mean HAI Titer - 65 and Older [Day 29 (28 days post-vaccination)]

      The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine

    19. Seroconversion - Ages 65-79 [Day 29 (28 days post-vaccination)]

      The proportion of subjects aged 65-79 achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer

    20. Seroconversion - Ages 80 and Older [Day 29 (28 days post-vaccination)]

      The proportion of subjects ages 80 and older achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer

    21. Seroprotection - Ages 65-79 [Day 29 (28 days post-vaccination)]

      Proportion of subjects ages 65-79 with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine

    22. Seroprotection - Ages 80 and Older [Day 29 (28 days post-vaccination)]

      Proportion of subjects ages 80 and older with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine

    23. Geometric Mean HAI Titer - Ages 65-79 [Day 29 (28 days post-vaccination)]

      The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine for ages 65-79

    24. Geometric Mean HAI Titer - Ages 80 and Older [Day 29 (28 days post-vaccination)]

      The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine for ages 80 and older

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    1. Persons aged ≥65 years, living in the community

    2. Intention of receiving IIV vaccine based on ACIP-CDC guidelines

    3. Willing to provide written informed consent prior to initiation of any study procedures

    4. Able to speak English

    5. Able and willing to complete baseline assessments and questionnaires, and to allow information to be collected from their electronic medical record

    6. Able and willing to complete post-vaccine assessments and questionnaires independently or with assistance

    7. Able and willing to have blood drawn for the study

    8. Able and willing to return in about one month for a follow-up visit including completing questionnaires and having another blood test

    9. Access to and ability to use a phone, independently or with assistance

    10. Adequate vision and motor skills to complete the diary form independently or with assistance.

    11. Not living in a skilled nursing facility/nursing home/long term acute care facility

    Exclusion Criteria:

    1. IIV receipt during the current influenza season prior to study enrollment

    2. Enrolled in this study during the 2017-18 (Year 1) influenza season

    Note: Year 1 study participants will only be enrolled in Year 2 if they are participating in the sub-study on repeat vaccination

    1. Has immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 12 months.

    2. Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematologic malignancy*

    *Participants with a history of malignancy may be included if, after previous treatment by surgical excision, chemotherapy or radiation therapy, the participant has been observed for a period that in the investigator's estimation provides a reasonable assurance of sustained cure (not less than 12 months)

    1. Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection

    2. History of febrile illness (> 100.0°F or 37.8°C) within the past 24 hours prior to IIV administration (temporary deferral)

    3. Contraindication to IIV receipt including history of severe allergic reaction after a previous dose of any influenza vaccine; or to a vaccine component*, including egg protein; or a latex allergy

    *Formaldehyde, Octylphenol ethoxylate, neomycin, kanamycin, barium, cetyltrimethlyammonium bromide (CTAB)

    1. Any history of Guillain-Barré syndrome

    2. Mild to severe dementia as determined by the Mini-Cog tool and the Rowland Universal Dementia Assessment Scale (RUDAS)

    3. Substance use that could interfere with study compliance

    4. Receipt of any inactivated licensed vaccine within 2 weeks, or live attenuated licensed vaccine within 4 weeks prior to enrollment in this study, or planning receipt of any vaccines during the 42-days post-vaccination period (including pneumococcal vaccines)

    5. Anyone who is already enrolled or plans to enroll in another clinical trial with an investigational product within 28 days of vaccine receipt. Co-enrollment in observational or behavioral intervention studies are allowed at any time while enrollment in a clinical trial involving an investigational product (other than vaccine) may occur after 30 days following vaccine receipt.

    6. Hearing loss determined by the investigators to prevent successful communication over the phone

    7. Any condition which, in the opinion of the investigators, may pose a health risk to the subject or interfere with the evaluation of the study objectives.

    8. Anyone who is a relative or subordinate of any research study personnel.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Centers for Disease Control and Prevention Atlanta Georgia United States 30333
    2 Boston Medical Center Boston Massachusetts United States 02118
    3 Duke University Durham North Carolina United States 27705
    4 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229

    Sponsors and Collaborators

    • Duke University
    • Centers for Disease Control and Prevention
    • Boston Medical Center
    • Children's Hospital Medical Center, Cincinnati

    Investigators

    • Principal Investigator: Kenneth Schmader, MD, Duke University
    • Principal Investigator: Theresa Harrington, MD, Centers for Disease Control and Prevention
    • Principal Investigator: Elizabeth Barnett, MD, Boston University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Duke University
    ClinicalTrials.gov Identifier:
    NCT03183908
    Other Study ID Numbers:
    • Pro00083845
    First Posted:
    Jun 12, 2017
    Last Update Posted:
    Mar 30, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Duke University
    influenza vaccine
    fever following vaccination
    pain following vaccination
    quality of life
    Additional relevant MeSH terms:
    Injection Site Reaction
    Drug-Related Side Effects and Adverse Reactions
    Vaccines

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Period Title: Overall Study
    STARTED 378 379
    COMPLETED 378 377
    NOT COMPLETED 0 2

    Baseline Characteristics

    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD) High-dose Influenza Vaccine (Fluzone HD) Total
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine Total of all reporting groups
    Overall Participants 378 379 757
    Age, Customized (Count of Participants)
    65-79 Years
    298
    78.8%
    296
    78.1%
    594
    78.5%
    80 or More
    80
    21.2%
    83
    21.9%
    163
    21.5%
    Sex: Female, Male (Count of Participants)
    Female
    213
    56.3%
    207
    54.6%
    420
    55.5%
    Male
    165
    43.7%
    172
    45.4%
    337
    44.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    1.9%
    1
    0.3%
    8
    1.1%
    Not Hispanic or Latino
    346
    91.5%
    351
    92.6%
    697
    92.1%
    Unknown or Not Reported
    25
    6.6%
    27
    7.1%
    52
    6.9%
    Race/Ethnicity, Customized (Count of Participants)
    Black only
    70
    18.5%
    59
    15.6%
    129
    17%
    Other
    22
    5.8%
    17
    4.5%
    39
    5.2%
    White Only
    286
    75.7%
    303
    79.9%
    589
    77.8%
    Region of Enrollment (participants) [Number]
    United States
    378
    100%
    379
    100%
    757
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Injection-Site Pain in Arm That Was Vaccinated, Population 1
    Description Comparison of the proportion of subjects reporting moderate/severe injection site pain within the first week post-vaccination in both treatment groups.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population 1
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 377
    None
    297
    78.6%
    282
    74.4%
    Mild
    69
    18.3%
    73
    19.3%
    Mod/Severe
    12
    3.2%
    22
    5.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments The null hypothesis is allV3 is inferior (i.e., allV3 will have higher rates of moderate/severe injection site pain) to IIV3-HD in regards to the proportion of subjects having moderate or severe injection site pain in the first week post vaccination.
    Type of Statistical Test Non-Inferiority
    Comments The one-sided non-inferiority test with the alpha level set at 0.025 and non-inferiority margin of 5%, stratified by site.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -5.8 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    2. Primary Outcome
    Title Number of Participants With Adverse Events of Clinical Interest, Population 2
    Description The frequency and descriptions of adverse events of clinical interest observed in the two treatment groups.
    Time Frame 42 days post-vaccination and compared between the two groups.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population 2
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 379
    Count of Participants [Participants]
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Observed Serious Adverse Events in Both Treatment Groups, Population 2
    Description The frequency and descriptions of serious adverse events observed in the two treatment groups. No analytical analysis was completed.
    Time Frame 42 days post-vaccination and compared between the two groups.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population 2
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 379
    Fall
    2
    0
    Metastatic squamous cell
    0
    1
    Post-operative ileus
    0
    1
    Respiratory Failure
    1
    0
    Stress induced cardiomyopathy
    1
    0
    TIA
    1
    0
    Chest Pain
    0
    1
    Asthma exacerbation
    1
    0
    Near syncope due to orthostasis
    1
    0
    Pulmonary emboli
    1
    0
    Small bowel obstruction
    1
    0
    SAEs related to study product
    0
    0
    SAEs not related to study product
    9
    3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®)
    Comments
    Type of Statistical Test Other
    Comments The comparison of the number of participants with reported SAEs regardless of relationship to study product were made using 95% confidence intervals. Results were reported using exact binomial confidence intervals.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Comparison of Frequencies
    Estimated Value 2.38
    Confidence Interval (2-Sided) 95%
    1.09 to 4.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection High-dose Influenza Vaccine (Fluzone® HD)
    Comments
    Type of Statistical Test Other
    Comments The comparison of the number of participants with reported SAEs regardless of relationship to study product were made using 95% confidence intervals. Results were reported using exact binomial confidence intervals.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Comparison of Frequencies
    Estimated Value .79
    Confidence Interval (2-Sided) 95%
    0.16 to 2.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    Title Number of Participants With H3N2 HAI Seroconversion
    Description H3N2 hemagglutination inhibition assay (HAI) seroconversion: The proportion of subjects achieving H3N2 seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer is > 1:10) in the respective season's vaccine
    Time Frame 29 days post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 342 338
    Count of Participants [Participants]
    112
    29.6%
    130
    34.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments
    Type of Statistical Test Non-Inferiority
    Comments This objective will be assessed using a one-sided noninferiority test with the alpha level set at 0.025 and noninferiority margin of 10%. The null hypothesis is the allV3 H3N2 seroconversion rate is inferior to IIV3-HD seroconversion rate.
    Statistical Test of Hypothesis p-Value 0.1245
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in Proportions
    Estimated Value -.0579
    Confidence Interval (1-Sided) 97.5%
    -.1291 to
    Parameter Dispersion Type:
    Value:
    Estimation Comments The directional comparison was the lower bound of the confidence interval using a 10% non-inferiority margin.
    5. Secondary Outcome
    Title Number of Participants With Local Reactions in Arm That Was Vaccinated - Full Study, Population 1
    Description Comparison of local reactions within the first week post-vaccination in both treatment groups.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population 1
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 377
    None
    348
    92.1%
    341
    90%
    Mild
    24
    6.3%
    23
    6.1%
    Mod/Severe
    6
    1.6%
    13
    3.4%
    None
    317
    83.9%
    326
    86%
    Mild
    44
    11.6%
    36
    9.5%
    Mod/Severe
    17
    4.5%
    15
    4%
    None
    335
    88.6%
    23
    6.1%
    Mild
    34
    9%
    26
    6.9%
    Mod/Severe
    9
    2.4%
    328
    86.5%
    None
    201
    53.2%
    196
    51.7%
    Mild
    150
    39.7%
    160
    42.2%
    Mod/Severe
    27
    7.1%
    21
    5.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Redness
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.9
    Confidence Interval (2-Sided) 98%
    -5.0 to 1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Shoulder Pain
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 98%
    -3.1 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Swelling
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.7
    Confidence Interval (2-Sided) 98%
    -7.5 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Tenderness
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.6
    Confidence Interval (2-Sided) 98%
    -2.7 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    6. Secondary Outcome
    Title Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 65 - 79, Population 1
    Description Comparison of local reactions within the first week post-vaccination in both treatment groups by age group.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Participants 65-79 years of age in Full Analysis Population 1
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD® adjuvanted influenza vaccine during Visit 1. FLUAD®: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone® High-Dose influenza vaccine during Visit 1. Fluzone® High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 298 294
    None
    274
    72.5%
    267
    70.4%
    Mild
    21
    5.6%
    17
    4.5%
    Mod/Severe
    3
    0.8%
    10
    2.6%
    None
    246
    65.1%
    249
    65.7%
    Mild
    36
    9.5%
    33
    8.7%
    Mod/Severe
    16
    4.2%
    12
    3.2%
    None
    264
    69.8%
    253
    66.8%
    Mild
    28
    7.4%
    22
    5.8%
    Mod/Severe
    6
    1.6%
    19
    5%
    None
    157
    41.5%
    138
    36.4%
    Mild
    117
    31%
    137
    36.1%
    Mod/Severe
    24
    6.3%
    19
    5%
    None
    232
    61.4%
    210
    55.4%
    Mild
    56
    14.8%
    65
    17.2%
    Mod/Severe
    10
    2.6%
    19
    5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Redness
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -5.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Shoulder Pain
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    -2.3 to 4.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Swelling
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.5
    Confidence Interval (2-Sided) 95%
    -8.1 to -1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Tenderness
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.6
    Confidence Interval (2-Sided) 95%
    -2.7 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Injection Site Pain
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -6.9 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    7. Secondary Outcome
    Title Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 80 +, Population 1
    Description Comparison of local reactions within the first week post-vaccination in both treatment groups by age group.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Participants 80+ years of age in Full Analysis Population 1
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 80 83
    None
    74
    19.6%
    74
    19.5%
    Mild
    3
    0.8%
    6
    1.6%
    Mod/Severe
    3
    0.8%
    3
    0.8%
    None
    71
    18.8%
    77
    20.3%
    Mild
    8
    2.1%
    3
    0.8%
    Mod/Severe
    1
    0.3%
    3
    0.8%
    None
    71
    18.8%
    75
    19.8%
    Mild
    6
    1.6%
    4
    1.1%
    Mod/Severe
    3
    0.8%
    4
    1.1%
    None
    44
    11.6%
    58
    15.3%
    Mild
    33
    8.7%
    23
    6.1%
    Mod/Severe
    3
    0.8%
    2
    0.5%
    None
    65
    17.2%
    72
    19%
    Mild
    13
    3.4%
    8
    2.1%
    Mod/Severe
    2
    0.5%
    3
    0.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Redness
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -7.3 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Shoulder Pain
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -9.5 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Swelling
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -8.6 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Tenderness
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -5.7 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Injection Site Pain
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -7.9 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    8. Secondary Outcome
    Title Number of Participants With Systemic Reactions - Full Study Population, Population 1
    Description Comparison of systemic reactions within the first week post-vaccination in both treatment groups.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Population 1: Four missing patient-reported outcome measures for "Fever" outcome.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 377
    None
    340
    89.9%
    346
    91.3%
    Mild
    20
    5.3%
    20
    5.3%
    Mod/Severe
    18
    4.8%
    11
    2.9%
    None
    362
    95.8%
    363
    95.8%
    Mild
    13
    3.4%
    9
    2.4%
    Mod/Severe
    3
    0.8%
    5
    1.3%
    None
    358
    94.7%
    359
    94.7%
    Mild
    15
    4%
    9
    2.4%
    Mod/Severe
    5
    1.3%
    9
    2.4%
    None
    319
    84.4%
    337
    88.9%
    Mild
    32
    8.5%
    25
    6.6%
    Mod/Severe
    27
    7.1%
    15
    4%
    None
    366
    96.8%
    358
    94.5%
    Mild
    11
    2.9%
    12
    3.2%
    Mod/Severe
    1
    0.3%
    3
    0.8%
    None
    335
    88.6%
    338
    89.2%
    Mild
    36
    9.5%
    31
    8.2%
    Mod/Severe
    7
    1.9%
    8
    2.1%
    None
    332
    87.8%
    344
    90.8%
    Mild
    28
    7.4%
    22
    5.8%
    Mod/Severe
    18
    4.8%
    11
    2.9%
    None
    334
    88.4%
    338
    89.2%
    Mild
    25
    6.6%
    22
    5.8%
    Mod/Severe
    19
    5%
    17
    4.5%
    None
    357
    94.4%
    362
    95.5%
    Mild
    19
    5%
    10
    2.6%
    Mod/Severe
    2
    0.5%
    5
    1.3%
    None
    374
    98.9%
    374
    98.7%
    Mild
    2
    0.5%
    1
    0.3%
    Mod/Severe
    2
    0.5%
    2
    0.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Arthralgia
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.8
    Confidence Interval (2-Sided) 98%
    -1.7 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Chills/Shivering
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 98%
    -2.8 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Diarrhea
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.1
    Confidence Interval (2-Sided) 98%
    -4.0 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Fatigue
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.2
    Confidence Interval (2-Sided) 98%
    -0.8 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Fever
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 98%
    -2.5 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Headache
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.3
    Confidence Interval (2-Sided) 98%
    -3.0 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Malaise
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.8
    Confidence Interval (2-Sided) 98%
    -1.7 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Myalgia
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 98%
    -3.3 to 4.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Nausea
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.8
    Confidence Interval (2-Sided) 98%
    -3.1 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Vomiting
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.0
    Confidence Interval (2-Sided) 98%
    -1.8 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    9. Secondary Outcome
    Title Number of Participants With System Reactions - Ages 65 - 79, Population 1
    Description Comparison of systemic reactions within the first week post-vaccination in both treatment groups by age group.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Participants 65-79 years of age in Full Analysis Population 1: Three missing "Fever" outcome values for the Fluzone HD group.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 298 294
    None
    266
    70.4%
    266
    70.2%
    Mild
    16
    4.2%
    19
    5%
    Mod/Severe
    16
    4.2%
    9
    2.4%
    None
    283
    74.9%
    282
    74.4%
    Mild
    12
    3.2%
    7
    1.8%
    Mod/Severe
    3
    0.8%
    5
    1.3%
    None
    280
    74.1%
    280
    73.9%
    Mild
    13
    3.4%
    7
    1.8%
    Mod/Severe
    5
    1.3%
    7
    1.8%
    None
    248
    65.6%
    258
    68.1%
    Mild
    27
    7.1%
    22
    5.8%
    Mod/Severe
    23
    6.1%
    14
    3.7%
    None
    288
    76.2%
    278
    73.4%
    Mild
    10
    2.6%
    10
    2.6%
    Mod/Severe
    0
    0%
    3
    0.8%
    None
    259
    68.5%
    257
    67.8%
    Mild
    32
    8.5%
    29
    7.7%
    Mod/Severe
    7
    1.9%
    8
    2.1%
    None
    260
    68.8%
    264
    69.7%
    Mild
    24
    6.3%
    19
    5%
    Mod/Severe
    14
    3.7%
    11
    2.9%
    None
    262
    69.3%
    261
    68.9%
    Mild
    20
    5.3%
    19
    5%
    Mod/Severe
    16
    4.2%
    14
    3.7%
    None
    280
    74.1%
    280
    73.9%
    Mild
    16
    4.2%
    9
    2.4%
    Mod/Severe
    2
    0.5%
    5
    1.3%
    None
    294
    77.8%
    291
    76.8%
    Mild
    2
    0.5%
    1
    0.3%
    Mod/Severe
    2
    0.5%
    2
    0.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Arthralgia
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.3
    Confidence Interval (2-Sided) 95%
    -1.1 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Chills/Shivering
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -3.0 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Diarrhea
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -3.5 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Fatigue
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.9
    Confidence Interval (2-Sided) 95%
    -1.1 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Fever
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -3.0 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Headache
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -3.2 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Malaise
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -2.5 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Myalgia
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -3.1 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Nausea
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -3.3 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Vomiting
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -1.8 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    10. Secondary Outcome
    Title Number of Participants With System Reactions - Ages 80 +, Population 1
    Description Comparison of systemic reactions within the first week post-vaccination in both treatment groups by age group.
    Time Frame Days 1 through 8 post-vaccination

    Outcome Measure Data

    Analysis Population Description
    Participants 80+ years of age in Full Analysis Population 1: One missing "Fever" outcome value in the Fluzone HD group. No statistical analysis completed on following Outcomes: Chills/Shivering, Headache, Nausea, Vomiting because none reported in this age group.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 80 83
    None
    74
    19.6%
    80
    21.1%
    Mild
    4
    1.1%
    1
    0.3%
    Mod/Severe
    2
    0.5%
    2
    0.5%
    None
    79
    20.9%
    81
    21.4%
    Mild
    1
    0.3%
    2
    0.5%
    Mod/Severe
    0
    0%
    0
    0%
    None
    78
    20.6%
    79
    20.8%
    Mild
    2
    0.5%
    2
    0.5%
    Mod/Severe
    0
    0%
    2
    0.5%
    None
    71
    18.8%
    79
    20.8%
    Mild
    5
    1.3%
    3
    0.8%
    Mod/Severe
    4
    1.1%
    1
    0.3%
    None
    78
    20.6%
    80
    21.1%
    Mild
    1
    0.3%
    2
    0.5%
    Mod/Severe
    1
    0.3%
    0
    0%
    None
    76
    20.1%
    81
    21.4%
    Mild
    4
    1.1%
    2
    0.5%
    Mod/Severe
    0
    0%
    0
    0%
    None
    72
    19%
    80
    21.1%
    Mild
    4
    1.1%
    3
    0.8%
    Mod/Severe
    4
    1.1%
    0
    0%
    None
    72
    19%
    77
    20.3%
    Mild
    5
    1.3%
    3
    0.8%
    Mod/Severe
    3
    0.8%
    3
    0.8%
    None
    77
    20.4%
    82
    21.6%
    Mild
    3
    0.8%
    1
    0.3%
    Mod/Severe
    0
    0%
    0
    0%
    None
    80
    21.2%
    83
    21.9%
    Mild
    0
    0%
    0
    0%
    Mod/Severe
    0
    0%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Arthralgia
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.05
    Confidence Interval (2-Sided) 95%
    -7.2 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Diarrhea
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -8.1 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Fatigue
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.7
    Confidence Interval (2-Sided) 95%
    -3.6 to 10.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Fever
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -2.4 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Malaise
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 5.0
    Confidence Interval (2-Sided) 95%
    2.0 to 12.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Myalgia
    Type of Statistical Test Non-Inferiority
    Comments Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -7.3 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.
    11. Secondary Outcome
    Title Quality of Life - Late Life Function & Disability Instrument - Full Population
    Description Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    LLFDI data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 138 141
    Activity Limitation
    -1.43
    -2.25
    Daily Activities
    -1.26
    -2.06
    Basic Mobility
    -1.37
    -2.43
    Participation Restriction
    -0.86
    -1.58
    Social Roles
    -0.77
    -1.80
    Instrumental Roles
    -1.08
    -1.66
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Activity Limitation Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.5862
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Daily Activities Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.5648
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Basic Mobility Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.4196
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Participation Restriction Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.2418
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Social Roles Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.0746
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Instrumental Roles Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.5497
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    12. Secondary Outcome
    Title Quality of Life - Late Life Function & Disability Instrument - Ages 65 - 79
    Description Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    Participants 65-79 years of age. LLFDI data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 119 120
    Activity Limitation
    -1.35
    -2.12
    Daily Activities
    -1.16
    -1.88
    Basic Mobility
    -1.33
    -2.29
    Participation Restriction
    -0.81
    -1.69
    Social Roles
    -0.66
    -1.98
    Instrumental Roles
    -1.00
    -1.70
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Activity Limitation Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.6278
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Daily Activities Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.5622
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Basic Mobility Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.5538
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Participation Restriction Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.2310
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Social Roles Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.0435
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Instrumental Roles Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.6519
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    13. Secondary Outcome
    Title Quality of Life - Late Life Function & Disability Instrument - Ages 80 +
    Description Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    Participants 80+ years of age. LLFDI data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 19 21
    Activity Limitation
    -1.94
    -2.99
    Daily Activities
    -1.86
    -3.13
    Basic Mobility
    -1.62
    -3.23
    Participation Restriction
    -1.17
    -0.97
    Social Roles
    -1.45
    -0.72
    Instrumental Roles
    -1.54
    -1.44
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Activity Limitation Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.7483
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Daily Activities Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.7483
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Basic Mobility Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.4953
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Participation Restriction Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.8669
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Social Roles Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.8451
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments Instrumental Roles Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.7376
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    14. Secondary Outcome
    Title Quality of Life - EQ-5D-5L -Full Population
    Description Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups (Year 1 only). Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    EQ-5D-5L data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 377
    Mean (95% Confidence Interval) [Change in score]
    -0.054
    -0.053
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments US Index Score Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.7407
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    15. Secondary Outcome
    Title Quality of Life - EQ-5D-5L - Ages 65 - 79
    Description Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    Participants 65-79 years of age. EQ-5D-5L data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 298 296
    Mean (95% Confidence Interval) [Change in score]
    -0.054
    -0.051
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments US Index Score Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.4032
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    16. Secondary Outcome
    Title Quality of Life - EQ-5D-5L - Ages 80 +
    Description Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only) Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    Participants 80+ years of age. EQ-5D-5L data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 80 83
    Mean (95% Confidence Interval) [Change in score]
    -0.055
    -0.062
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments US Index Score Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.4079
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    17. Secondary Outcome
    Title Quality of Life - EQ VAS -Full Population
    Description Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    EQ VAS data collected for only one year.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 378 377
    Mean (95% Confidence Interval) [Change in score]
    -2.222
    -2.496
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments EQ VAS Changes for Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.7948
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    18. Secondary Outcome
    Title Quality of Life - EQ VAS - Ages 65 - 79
    Description Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    Participants 65-79 years of age.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 298 296
    Mean (95% Confidence Interval) [Change in score]
    -2.474
    -2.791
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments EQ VAS Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. Alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.7953
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    19. Secondary Outcome
    Title Quality of Life - EQ VAS - Ages 80 +
    Description Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).
    Time Frame Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

    Outcome Measure Data

    Analysis Population Description
    Participants 80+ years of age.
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 80 83
    Mean (95% Confidence Interval) [Change in score]
    -1.295
    -1.463
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
    Comments EQ VAS Changes from Day 1 to Day 3 Group Comparisons
    Type of Statistical Test Superiority
    Comments Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
    Statistical Test of Hypothesis p-Value 0.9329
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    20. Secondary Outcome
    Title Seroconversion - 65 and Older
    Description The proportion of subjects achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 342 338
    A/H1N1
    28.1
    7.4%
    26.6
    7%
    Influenza B
    18.7
    4.9%
    23.4
    6.2%
    21. Secondary Outcome
    Title Seroprotection - 65 and Older
    Description Proportion of subjects with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 342 338
    A/H1N1 - Baseline
    69.6
    18.4%
    66.9
    17.7%
    A/H1N1 - Post-vaccination
    83.3
    22%
    83.4
    22%
    A/H3N2 - Baseline
    66.7
    17.6%
    65.7
    17.3%
    A/H3N2 - Post-vaccination
    89.8
    23.8%
    88.5
    23.4%
    Influenza B - Baseline
    24.6
    6.5%
    26.9
    7.1%
    Influenza B - Post-vaccination
    44.2
    11.7%
    48.8
    12.9%
    22. Secondary Outcome
    Title Geometric Mean HAI Titer - 65 and Older
    Description The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 342 338
    A/H1N1 - Baseline
    51.8
    50.8
    A/H1N1 - Post-vaccination
    100.0
    98.0
    A/H3N2 - Baseline
    63.4
    58.5
    A/H3N2 - Post-vaccination
    141.7
    177.3
    Influenza B - Baseline
    13.4
    14.7
    Influenza B - Post-vaccination
    21.6
    27.5
    23. Secondary Outcome
    Title Seroconversion - Ages 65-79
    Description The proportion of subjects aged 65-79 achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 269 261
    A/H1N1
    29.7
    7.9%
    27.2
    7.2%
    A/H3N2
    34.2
    9%
    39.5
    10.4%
    Influenza B
    19.0
    5%
    26.1
    6.9%
    24. Secondary Outcome
    Title Seroconversion - Ages 80 and Older
    Description The proportion of subjects ages 80 and older achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 73 77
    A/H1N1
    21.9
    5.8%
    24.7
    6.5%
    A/H3N2
    27.4
    7.2%
    35.1
    9.3%
    Influenza B
    17.8
    4.7%
    14.3
    3.8%
    25. Secondary Outcome
    Title Seroprotection - Ages 65-79
    Description Proportion of subjects ages 65-79 with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 269 261
    A/H1N1 - Baseline
    69.9
    18.5%
    65.5
    17.3%
    A/H1N1 - Post-vaccination
    83.6
    22.1%
    82.8
    21.8%
    A/H3N2 - Baseline
    67.3
    17.8%
    65.5
    17.3%
    A/H3N2 - Post-vaccination
    91.4
    24.2%
    88.1
    23.2%
    Influenza B - Baseline
    22.3
    5.9%
    19.9
    5.3%
    Influenza B - Post-vaccination
    42.4
    11.2%
    45.2
    11.9%
    26. Secondary Outcome
    Title Seroprotection - Ages 80 and Older
    Description Proportion of subjects ages 80 and older with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 73 77
    A/H1N1 - Baseline
    68.5
    18.1%
    71.4
    18.8%
    A/H1N1 - Post-vaccination
    82.2
    21.7%
    85.7
    22.6%
    A/H3N2 - Baseline
    64.4
    17%
    66.2
    17.5%
    A/H3N2 - Post-vaccination
    83.6
    22.1%
    89.6
    23.6%
    Influenza B - Baseline
    32.9
    8.7%
    50.6
    13.4%
    Influenza B - Post-vaccination
    50.7
    13.4%
    61.0
    16.1%
    27. Secondary Outcome
    Title Geometric Mean HAI Titer - Ages 65-79
    Description The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine for ages 65-79
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 269 261
    A/H1N1 - Baseline
    52.5
    49.5
    A/H1N1 - Post-vaccination
    108.8
    100.9
    A/H3N2 - Baseline
    63.3
    56.4
    A/H3N2 - Post-vaccination
    145.3
    184.4
    Influenza B - Baseline
    12.2
    11.8
    Influenza B - Post-vaccination
    20.3
    23.8
    28. Secondary Outcome
    Title Geometric Mean HAI Titer - Ages 80 and Older
    Description The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine for ages 80 and older
    Time Frame Day 29 (28 days post-vaccination)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.
    Arm/Group Title Influenza Vaccine, Adjuvanted (FLUAD®) High-Dose Influenza Vaccine (Fluzone HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    Measure Participants 73 77
    A/H1N1 - Baseline
    49.3
    55.6
    A/H1N1 - Post-vaccination
    73.4
    88.7
    A/H3N2 - Baseline
    63.7
    66.5
    A/H3N2 - Post-vaccination
    129.2
    155.0
    Influenza B - Baseline
    18.7
    31.2
    Influenza B - Post-vaccination
    27.0
    45.0

    Adverse Events

    Time Frame Adverse Events, Serious Adverse Events, and All-Cause Mortality rates were collected 42 days post vaccination. Serious Adverse Events and Mortality Rates were collected up to 181 days for the longer-term immunogenicity subset
    Adverse Event Reporting Description The two reported deaths occurred >42 days post vaccination
    Arm/Group Title Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Arm/Group Description In the study arm, subjects will receive a single dose of FLUAD® adjuvanted influenza vaccine during Visit 1. FLUAD®: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine In the study arm, subjects will receive a single dose of Fluzone® High-Dose influenza vaccine during Visit 1. Fluzone® High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
    All Cause Mortality
    Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/378 (0.3%) 1/379 (0.3%)
    Serious Adverse Events
    Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/378 (2.6%) 4/379 (1.1%)
    Blood and lymphatic system disorders
    Metastatic squamous cell 0/378 (0%) 0 1/379 (0.3%) 1
    Cardiac disorders
    Chest Pain 1/378 (0.3%) 1 1/379 (0.3%) 1
    Stressed induced cardiomyopathy 1/378 (0.3%) 1 0/379 (0%) 0
    Gastrointestinal disorders
    Post-operative ileus 0/378 (0%) 0 1/379 (0.3%) 1
    Small bowel obstruction 1/378 (0.3%) 1 1/379 (0.3%) 1
    General disorders
    Fall 2/378 (0.5%) 2 0/379 (0%) 0
    Nervous system disorders
    TIA 1/378 (0.3%) 1 0/379 (0%) 0
    Near syncope due to orthostatic 1/378 (0.3%) 1 0/379 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory Failure 1/378 (0.3%) 1 0/379 (0%) 0
    Asthma exacerbation 1/378 (0.3%) 1 0/379 (0%) 0
    Pulmonary emboli 1/378 (0.3%) 1 0/379 (0%) 0
    Other (Not Including Serious) Adverse Events
    Adjuvanted Influenza Vaccine (FLUAD®) High-dose Influenza Vaccine (Fluzone® HD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/378 (4%) 19/379 (5%)
    Respiratory, thoracic and mediastinal disorders
    Cold 15/378 (4%) 15 19/379 (5%) 19

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Kenneth Schmader
    Organization Duke University
    Phone 919-660-7572
    Email kenneth.schmader@duke.edu
    Responsible Party:
    Duke University
    ClinicalTrials.gov Identifier:
    NCT03183908
    Other Study ID Numbers:
    • Pro00083845
    First Posted:
    Jun 12, 2017
    Last Update Posted:
    Mar 30, 2021
    Last Verified:
    Mar 1, 2021