Recombinant Influenza Vaccination in U.S. Nursing Homes

Study Overview
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Brief Summary
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Based on recent evidence on the mutation of the A/H3N2 strain in egg-grown vaccine, the investigators will study the quadrivalent recombinant influenza vaccine (RIV4, Flublok) compared to the standard dose quadrivalent vaccine (IV4) in a cohort of long-stay NH residents with a primary endpoint of all-cause hospitalization.

Detailed Description
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A study sample goal of 1000 U.S. NHs, housing approximately 112,000 overall residents and 92,000 over the age of 65 years, of whom 64,500 are long-stay NH residents, will be recruited for each of the 2019-20 and 2020-21 influenza seasons. Participating facilities will be randomly allocated in a 1:1 ratio to RIV4 or IV4 vaccine for their residents. Also, all staff must be offered the same vaccine in both allocation groups, in order to eliminate differences in transmission of influenza through staff to residents related to differences in vaccine-related protection of staff and will reduce heterogeneity between clusters. The Minimum Data Set from the NH resident assessment instrument will be evaluated from all evaluable facilities meeting inclusion criteria and will be cross-referenced to Medicare claims and drug use data.

Official Title
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Comparative Effectiveness of Recombinant Versus Standard Dose Quadrivalent Influenza Vaccine in U.S. Nursing Homes

Conditions
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Influenza, Influenza -Like Illness, Influenza, Human

Intervention / Treatment
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* Biological: Recombinant Influenza Vaccine
* Biological: Standard Dose Quadrivalent Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medicare-certified NHs with at least 50 long-stay residents ≥ 18 years of age Facilities with at least 80% of their long-stay population ≥ 65 years of age or at least 70 long stay residents ≥ 65 years of age that make up ≥ 45% of their total number of beds Exclusion Criteria: Hospital-based facilities Facilities where Fluzone High-Dose or Fluad was used in the previous influenza season (2018-19 or 2019-20), or who's leadership plans to use one of these vaccines in the 2019- 2020 or 2020-21 season Facilities not submitting MDS data Facilities not in one of the 50 U.S. states

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIV4<br>Nursing homes randomized to receive quadrivalent recombinant influenza vaccine (Flublok) for the residents and staff | Biological: Recombinant Influenza Vaccine<br>* Nursing home residents and staff 18 years and older are allocated to receive quadrivalent recombinant influenza vaccine.<br>* Other names: RIV4;|
| Active Comparator: IV4<br>Nursing homes randomized to receive standard dose quadrivalent influenza vaccine for the residents and staff | Biological: Standard Dose Quadrivalent Influenza Vaccine<br>* Nursing home residents and staff 18 years and older are allocated to receive standard dose quadrivalent influenza vaccine<br>* Other names: IV4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in all-cause hospitalization rates during the 2019-20 and 2020-21 influenza seasons | To determine the differences in all-cause hospitalization rates during the 2019-20 and 2020-21 influenza seasons experienced by all long-stay nursing home residents 18 years of age and older in facilities randomized to offer either quadrivalent recombinant influenza vaccine (RIV4) or standard dose quadrivalent influenza vaccine (IV4). | Up to 8 months each influenza season | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in each pneumonia and influenza-related hospitalization rates | To determine the differences in each pneumonia and influenza-related hospitalization rates during the 2019-20 and 2020-21 influenza seasons experienced by long-stay nursing home residents in facilities randomized to either RIV4 or IV4 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in pneumonia-related hospitalization rates | To determine the differences in each pneumonia-related hospitalization rates during the 2019-20 and 2020-21 influenza seasons experienced by long-stay nursing home residents in facilities randomized to either RIV4 or IV4 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in major adverse cardiovascular event-related (MACE) hospitalization rates | To determine the differences in each major adverse cardiovascular event-related (MACE) hospitalization rates during the 2019-20 and 2020-21 influenza seasons experienced by long-stay nursing home residents in facilities randomized to either RIV4 or IV4 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in cardiorespiratory-related hospitalization rates | To determine the differences in long-stay residents' cardiorespiratory-related hospitalization rates each season and across two seasons in facilities randomized to either RIV4 or IV4 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in ICU stay | To determine the differences in long-stay residents' ICU stay each season and across two seasons in facilities randomized to either RIV4 or IV4 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in mortality rates | To determine the differences in long-stay residents' mortality rates each influenza season and both seasons in facilities randomized to either RIV4 or IV4 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in activities of daily living (ADL) function score | To determine the differences in long-stay residents' composite Activities of Daily Living (ADL) function score based on the MDS experienced during the influenza season by selected comorbidities and specific to respiratory illness, in facilities randomized to either RIV4 or IV4 combined over two seasons for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 
| Differences in facility-reported outbreaks | To determine differences in facility-reported outbreaks each season and across two seasons in facilities randomized to either RIV4 or IV4 | Up to 8 months each influenza season | 
| Differences in all-cause hospitalization rates | To determine differences in long-stay residents' all-cause hospitalization rates as an interim exploratory analysis based on the Minimum Data Set 3.0 for each, residents 18 years of age and older and those 65 years of age and older. | Up to 8 months each influenza season | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Vaccine, Vaccination, Nursing Home, Respiratory-Related Hospitalizations, Cluster Randomized Trial, MACE (Major Adverse Cardiovascular Event), Cardiorespiratory-Related Hospitalizations, All-Cause Hospitalization