Clinical trial NCT03183908: FLUAD® vs. Fluzone® High-Dose Study
Official title: Safety and Immunogenicity of Adjuvanted Versus High-Dose Inactivated Influenza Vaccines in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain
Quality of Life
Injection Site Reaction
Side Effect of Drug
Adverse Drug Event
Keywords: influenza vaccine
fever following vaccination
pain following vaccination
quality of life
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: Boston Medical Center
name: Children's Hospital Medical Center, Cincinnati
First posted: 2017-06-12
Enrollment: 757
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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
3. 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.
4. 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)
5. Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection
6. History of febrile illness (\> 100.0°F or 37.8°C) within the past 24 hours prior to IIV administration (temporary deferral)
7. 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)
8. Any history of Guillain-Barré syndrome
9. Mild to severe dementia as determined by the Mini-Cog tool and the Rowland Universal Dementia Assessment Scale (RUDAS)
10. Substance use that could interfere with study compliance
11. 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)
12. 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.
13. Hearing loss determined by the investigators to prevent successful communication over the phone
14. 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.
15. Anyone who is a relative or subordinate of any research study personnel.

Primary outcomes:
measure: Number of Participants With Injection-Site Pain in Arm That Was Vaccinated, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Number of Participants With Adverse Events of Clinical Interest, Population 2
timeFrame: 42 days post-vaccination and compared between the two groups.
measure: Observed Serious Adverse Events in Both Treatment Groups, Population 2
timeFrame: 42 days post-vaccination and compared between the two groups.
measure: Number of Participants With H3N2 HAI Seroconversion
timeFrame: 29 days post-vaccination
Secondary outcomes:
measure: Number of Participants With Local Reactions in Arm That Was Vaccinated - Full Study, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 65 - 79, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 80 +, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Number of Participants With Systemic Reactions - Full Study Population, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Number of Participants With System Reactions - Ages 65 - 79, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Number of Participants With System Reactions - Ages 80 +, Population 1
timeFrame: Days 1 through 8 post-vaccination
measure: Quality of Life - Late Life Function & Disability Instrument - Full Population
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - Late Life Function & Disability Instrument - Ages 65 - 79
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - Late Life Function & Disability Instrument - Ages 80 +
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - EQ-5D-5L -Full Population
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - EQ-5D-5L - Ages 65 - 79
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - EQ-5D-5L - Ages 80 +
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - EQ VAS -Full Population
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - EQ VAS - Ages 65 - 79
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Quality of Life - EQ VAS - Ages 80 +
timeFrame: Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)
measure: Seroconversion - 65 and Older
timeFrame: Day 29 (28 days post-vaccination)
measure: Seroprotection - 65 and Older
timeFrame: Day 29 (28 days post-vaccination)
measure: Geometric Mean HAI Titer - 65 and Older
timeFrame: Day 29 (28 days post-vaccination)
measure: Seroconversion - Ages 65-79
timeFrame: Day 29 (28 days post-vaccination)
measure: Seroconversion - Ages 80 and Older
timeFrame: Day 29 (28 days post-vaccination)
measure: Seroprotection - Ages 65-79
timeFrame: Day 29 (28 days post-vaccination)
measure: Seroprotection - Ages 80 and Older
timeFrame: Day 29 (28 days post-vaccination)
measure: Geometric Mean HAI Titer - Ages 65-79
timeFrame: Day 29 (28 days post-vaccination)
measure: Geometric Mean HAI Titer - Ages 80 and Older
timeFrame: Day 29 (28 days post-vaccination)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Centers for Disease Control and Prevention
state: Georgia
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Duke University
name: Kenneth Schmader, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centers for Disease Control and Prevention
name: Theresa Harrington, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston University
name: Elizabeth Barnett, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmader KE, Liu CK, Harrington T, Rountree W, Auerbach H, Walter EB, Barnett ED, Schlaudecker EP, Todd CA, Poniewierski M, Staat MA, Wodi P, Broder KR. Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2031266. doi: 10.1001/jamanetworkopen.2020.31266.