Recombinant vs Egg-Based Quadrivalent Influenza Vaccination for Nursing Home Residents: A Cluster Randomized Trial.

Importance: Influenza vaccination remains the most important intervention to prevent influenza morbidity and mortality among nursing home residents. The additional effectiveness of recombinant influenza vaccine vs standard dose vaccines was demonstrated in outpatient older adults but has not been evaluated in nursing home populations. Objective: To compare hospitalization rates among residents in nursing homes immunized with a recombinant vs a standard dose egg-based influenza vaccine. Design, Setting, and Participants: This pragmatic cluster randomized trial assessed nursing home residents 65 years or older residing in a US facility for 100 or more days before the start of influenza season (October 1). The study was conducted across the 2019 to 2020 and 2020 to 2021 influenza seasons and randomly assigned nursing homes 1:1 within blocks categorized by proportion of Black residents and prior resident hospitalization rates. Medicare claims data were used to evaluate resident-level hospitalization outcomes. Enrollment and allocation to treatment groups began on July 20, 2019. Data analysis began on January 1, 2021, with primary end points finalized June 30, 2024. Intervention: Nursing homes were cluster randomized to vaccinate all residents with recombinant quadrivalent influenza vaccine (RIV4) or standard egg-based quadrivalent inactivated influenza vaccine (IIV4). Main Outcome and Measures: The primary outcome was respiratory-related hospitalization. Secondary outcomes included death and hospitalization due to any cause. Results: A total of 144 565 person observations (mean [SD] age, 77.4 [13.1] years; 63.0% female) at 1078 nursing homes were included, with 72 005 residents in nursing homes randomized to provide RIV4 and 72 560 residents in nursing home randomized to provide IIV4. In total, 85.6% of the residents received influenza vaccination. Baseline resident characteristics were comparable across treatment groups. For the primary end point of respiratory-related hospitalizations, there were 1387 hospitalizations (1.9%) in the RIV4 group vs 1424 (2.0%) in the IIV4 group (hazard ratio, 1.01; 95% CI, 0.62-2.17). Hospitalization rates by vaccine were similar for other hospitalization outcomes and death, overall, and by season and subgroups (gender, race, and comorbidities). Conclusions and Relevance: In this cluster randomized trial of nursing homes, there was no significant difference between recombinant or standard dose vaccine for reducing hospitalizations associated with influenza illness. However, the COVID-19 pandemic restricting influenza activity along with poor vaccine match to circulating strains substantially limits the conclusions. Trial Registration: Clinicaltrials.gov Identifier: NCT03965195.