Influenza
Conditions
Keywords
Randomized Controlled Trial, Influenza, Influenza vaccine, Flu Vaccine, Fluzone, HD Fluzone, Nursing Homes, Hospitalization, Mortality, Health Care worker vaccination, ADL decline, Pilot, Effectiveness
Brief summary
The purpose of this pilot evaluation is to help determine the feasibility and power needed to prospectively evaluate relative effectiveness of high-dose influenza vaccine in preventing influenza mortality and hospitalization in a nursing home population in the U.S., compared to the standard-dose influenza vaccine.
Detailed description
Influenza remains the most common preventable respiratory viral infection of older adults. Older adults incur more than 90% of the disease burden, and those residing in nursing homes are the most affected subset given their immune senescence, multi-morbidity, and close living quarters. Each year, the majority of influenza-related hospitalizations occur during the period with the greatest influenza activity. Influenza vaccination has been associated with reduced hospitalization, strokes, heart attacks and death in non-institutional older adult populations, but the benefit of influenza vaccine for the oldest population has been questioned. The new high-dose influenza vaccine is considerably more immunogenic in older adults, and has recently been approved for use in individuals aged 65 years and older. No clinical data yet confirm whether the improved immunogenicity translates into added clinical benefit, such as further reduction in hospitalization or death. Estimating the benefit of influenza vaccination among older adults in long-term care settings using randomized controlled trials requires extensive effort and is costly. Instead, a pragmatic RCT in a nursing home population has several advantages as a model for comparing therapeutic approaches. This clinical trial aims to test the feasibility of our protocol for a subsequent larger study. We aim to demonstrate that we can recruit and enroll facilities; randomly assign and coordinate vaccine delivery; collect data; conduct site audits for data validation; create outcomes using multiple data sources; and conduct analyses.
Interventions
BIOLOGICALHD Fluzone Vaccine
Nursing home residents over 65 years are allocated to receive high dose trivalent vaccine. Residents under 65 years are provided standard dose trivalent vaccine (TIV).
BIOLOGICALSD Fluzone Vaccine
Nursing home residents are allocated to receive standard trivalent vaccine (TIV).
Sponsors
Brown University
Insight Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Long-term care facilities in one of the 122 cities that serve as Center for Disease Control and Prevention (CDC) surveillance sites
Exclusion criteria
* Facilities already systematically administering HD vaccine to their residents * Facilities for whom over half the residents are on Medicare (short-stay) * Facilities in which over half the residents are on Medicare Part A (SNF) * Facilities having fewer than 50 long-stay residents * Hospital-based facilities * Facilities with more than 20% of the population under age 65 * Facilities with mandated (employment-dependent) seasonal influenza vaccination * Facilities not submitting MDS data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total All-cause Hospitalizations | 1 year | The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Residents' Functional Status | 1 year | The secondary outcome will establish our methodology for measuring change in functional status of nursing home residents using Activities of Daily Living (ADL) data in the Minimum Data Set (MDS). A change in functional status is defined as a decline in physical functioning by at least 4 points on the 28-point ADL scale. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size | 1 year | This outcome evaluates our ability to recruit and enroll nursing facilities that meet our inclusion and exclusion criteria, and ensure nursing home residents receive either high-dose or standard-dose influenza vaccine |
Countries
United States
Participant flow
Recruitment details
Cluster--We included nursing homes (NHs) within 50 miles of a CDC surveillance. We identified and contacted individual facilities and organizations. Each recruited NH completed a site feasibility form and was notified of its eligibility based on the exclusion criteria. Subject--Eligible nursing home residents in each participating facility.
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Vaccine for Residents NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents. | 1,461 |
| High-Dose Vaccine for Residents NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents. | 20 |
| Standard-dose for Residents NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents. | 1,496 |
| Standard-dose for Residents NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents. | 19 |
| Total | 2,996 |
Baseline characteristics
| Characteristic | High-Dose Vaccine for Residents | Standard-dose for Residents | Total |
|---|---|---|---|
| Age, Customized Average age | 84.5 years STANDARD_DEVIATION 8.4 | 83.4 years STANDARD_DEVIATION 8.7 | 84.0 years STANDARD_DEVIATION 8.6 |
| Number of long-stay residents who are over 65 years of age | 78 participants STANDARD_DEVIATION 37 | 78 participants STANDARD_DEVIATION 44 | 78 participants STANDARD_DEVIATION 40 |
| Number of nursing facilities that are part of a chain | 10 nursing homes | 6 nursing homes | 16 nursing homes |
| Number of residents per nursing home | 108 participants STANDARD_DEVIATION 49 | 124 participants STANDARD_DEVIATION 54 | 116 participants STANDARD_DEVIATION 51 |
| Percent of residents in for-profit nursing facilities | 70.0 percent STANDARD_DEVIATION 47 | 73.6 percent STANDARD_DEVIATION 45.2 | 71.8 percent STANDARD_DEVIATION 45.6 |
| Percent of residents who are long-stay | 88.0 percent STANDARD_DEVIATION 6.5 | 86.5 percent STANDARD_DEVIATION 12.1 | 87.2 percent STANDARD_DEVIATION 9.7 |
| Percent of residents with Medicaid as payer | 62.5 percent STANDARD_DEVIATION 12.8 | 62.9 percent STANDARD_DEVIATION 17.4 | 62.7 percent STANDARD_DEVIATION 15 |
| Sex/Gender, Customized Percent of female nursing home residents | 1094 Participants | 1113 Participants | 2207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 249 / 1,461 | 274 / 1,496 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Total All-cause Hospitalizations
The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).
Time frame: 1 year
Population: We identified long-stay nursing home residents and evaluated outcomes (e.g. hospitalizations, functional status).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-Dose Vaccine for Residents | Total All-cause Hospitalizations | 197 events |
| Standard-dose for Residents | Total All-cause Hospitalizations | 301 events |
Secondary
Change in Residents' Functional Status
The secondary outcome will establish our methodology for measuring change in functional status of nursing home residents using Activities of Daily Living (ADL) data in the Minimum Data Set (MDS). A change in functional status is defined as a decline in physical functioning by at least 4 points on the 28-point ADL scale.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-Dose Vaccine for Residents | Change in Residents' Functional Status | 196 Participants |
| Standard-dose for Residents | Change in Residents' Functional Status | 206 Participants |
Other Pre-specified
Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size
This outcome evaluates our ability to recruit and enroll nursing facilities that meet our inclusion and exclusion criteria, and ensure nursing home residents receive either high-dose or standard-dose influenza vaccine
Time frame: 1 year
Population: Nursing home facilities randomized to receive high dose or standard dose vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-Dose Vaccine for Residents | Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size | 20 Nursing Homes |
| Standard-dose for Residents | Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size | 19 Nursing Homes |