Feasibility of a cluster-randomized influenza vaccination trial in U.S. nursing homes: Lessons learned.

Influenza severity increases and vaccine effectiveness decreases with age. High-dose influenza vaccine (HD) with quadruple the antigen of standard-dose (SD) vaccine is more efficacious in community-dwelling persons 65 years and older. We evaluated the feasibility of recruiting and randomizing Medicare certified nursing homes (NHs) for a pragmatic cluster-randomized trial comparing HD vs. SD (NCT1720277). Residents were long-stay and at least 65 years old. NH leadership agreed to standard of care random assignment with HD (Fluzone® High-Dose) or SD (Fluzone®) influenza vaccine for their facility for the 2012-2013 influenza season. We used Minimum Data Set (MDS) 3.0 and Vital Status records for pre-specified clinical outcomes: 1) all-cause hospitalization, 2) NH mortality, and 3) functional decline. Intent-to-treat analyses were performed at the resident-level using Cox proportional hazards, multivariable Poisson, and logistic regression models accounting for clustering by facility. We randomized 39 NHs (19 SD and 20 HD), coordinated vaccine delivery, implemented web-based data collection, and accessed MDS data, demonstrating feasibility. There were 2,957 eligible residents (SD 1496; HD 1461); characteristics were similar between groups. A total of 301 (20.1%) of SD and 197 (13.5%) of HD allocated residents were ever hospitalized, (adjusted relative risk 0.680; 95% CI: 0.537, 0.862; p = 0.001). NH mortality was 274 (18.3%) SD vs. 249 (17.1%) HD, adjusted relative risk 0.834; 95% CI: 0.678, 1.027; p = 0.087). There were no differences in decline in functional status (13.4 vs. 13.8%, adjusted relative risk 0.994; 95% CI: 0.774,1.278; p = 0.965). We demonstrate that a pragmatic large-scale trial is feasible in a NH setting.