A cluster randomized controlled trial comparing relative effectiveness of two licensed influenza vaccines in US nursing homes: Design and rationale.

BACKGROUND: Influenza, the most important viral infection affecting older adults, produces a substantial burden in health care costs, morbidity, and mortality. Influenza vaccination remains the mainstay in prevention and is associated with reduced rates of hospitalization, stroke, heart attack, and death in non-institutional older adult populations. Influenza vaccination produces considerably lower antibody response in the elderly compared to young adults. Four-fold higher vaccine antigen (high-dose) than in the standard adult vaccine (standard-dose) elicits higher serum antibody levels and antibody response in ambulatory elderly. PURPOSE: To describe the design considerations of a large clinical trial of high-dose compared to standard-dose influenza vaccine in nursing homes and baseline characteristics of participating nursing homes and long-stay (more than 90 days) residents over 65 years of age. METHODS: The high-dose influenza vaccine intervention trial is multifacility, cluster randomized controlled trial with a 2×2 factorial design that compares hospitalization rates, mortality, and functional decline among long-stay nursing home residents in facilities randomized to receive high-dose versus standard-dose influenza vaccine and also randomized with or without free staff vaccines provided by study organizers. Enrollment focused on nursing homes with a large long-stay resident population over 65 years of age. The primary outcome is the resident-level incidence of hospitalization with a primary diagnosis of pulmonary and influenza-like illness, based upon Medicare inpatient hospitalization claims. Secondary outcomes are all-cause mortality based upon the vital status indicator in the Medicare Vital Status file, all-cause hospitalization directly from the nursing home Minimum Data Set discharge records, and the probability of declining at least 4 points on the 28-point Activities of Daily Living Scale. RESULTS: Between February and September 2013, the high-dose influenza vaccine trial recruited and randomized 823 nursing homes. The analysis sample includes 53,035 long-stay nursing home residents over 65 years of age, representing 57.7% of the participating facilities' population. Residents are mainly women (72.2%), white (75.5%), with a mean age of 83 years. Common conditions include hypertension (79.2%), depression (55.1%), and diabetes mellitus (34.4%). The prevalence of circulatory and pulmonary disorders includes heart failure (20.5%), stroke (20.1%), and asthma/chronic obstructive pulmonary disease (20.2%). CONCLUSIONS: This high-dose influenza vaccine trial uniquely offers a paradigm for future studies of clinical and programmatic interventions within the framework of efforts designed to test the impact of changes in usual treatment practices adopted by health care systems. TRIAL REGISTRATION: NCT01815268.

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.

Hypertension treatment and outcomes in US nursing homes: results from the US National Nursing Home Survey.

OBJECTIVES: The objective of this study was to describe antihypertensive medication use, determine what effects comorbid illness has on prescribing of commonly used antihypertensive medications, and explore how treatment affected selected clinical and functional outcomes in US nursing home residents. DESIGN: Cross-sectional observational study using data from the 2004 National Nursing Home Survey, a nationally representative sample of US nursing home residents. RESULTS: More than one half, 53.8%, of all residents had hypertension as a primary admission or current diagnosis. A large majority (84%) of residents with the diagnosis of hypertension were receiving at least one legend medication indicated for hypertension. The most common selection of pharmacologic agent was monotherapy with diuretics in 11% of all residents receiving antihypertensive medications. Hypertensive residents with a diagnosis of arrhythmia (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.02-1.38), stroke (OR = 1.18, 95% CI = 1.05-1.34), or heart failure (OR = 1.17, 95% CI = 1.04-1.32) were more likely to be receiving a beta blocker. Those with diabetes (OR = 0.86, 95% CI = 0.77-0.96), depression (OR = 0.78, 95% CI = 0.70-0.87), constipation (OR = 0.72, 95% CI = 0.61-0.84), or asthma (OR = 0.51, 95% CI = 0.34-0.74) were less likely to be receiving a beta blocker. Hospital admission was less likely (OR = 0.50, 95% CI = 0.36-0.69) when residents were taking any commonly used antihypertensive medication (diuretics, beta blockers, angiotensin-converting enzyme/angiotensin receptor blockers [ACE/ARBs], calcium channel blockers, or alpha-blockers) but significantly more likely when therapy included a beta blocker (OR = 1.45, 95% CI = 1.18 - 1.78). Beta blockers were associated with an increased likelihood of falls (OR = 1.14, 95% CI = 1.04-1.27) and a decreased likelihood of constipation (OR 0.72, 95% CI = 0.61-0.84). Beta blockers were associated with a decreased likelihood of depression (OR 0.83, 95% CI = 0.74-0.92) as was the use of any commonly used antihypertensive (OR = 0.76, 95% CI = 0.63-0.90). CONCLUSION: Hypertension is prevalent in US nursing home residents and most residents with that diagnosis (84%) are being treated with antihypertensive medication. Through examination of the National Nursing Home Survey database, associations between the use of selected antihypertensive medication, comorbid illness, and specified outcomes were observed.