Background: Despite strong evidence of clinical benefit, influenza vaccination rates remain suboptimal in the United States. Randomized trials suggest that behavioral nudges may improve vaccination rates, particularly when messaging includes language on the potential cardiovascular (CV) benefits of vaccination. Whether these nudges are effective in a diverse US population is unknown.
Purpose: The Kaiser Permanente VACCination Improvement with Nudge-based CardiovAscular Targeted Engagement (KP-VACCINATE) study tested the effectiveness and timing of electronically-delivered health system messaging highlighting the potential CV benefits of vaccination (CV-focused communication) vs usual care communication on influenza vaccination uptake across two integrated healthcare delivery systems.
Methods: KP-VACCINATE is a multicenter, randomized controlled megatrial conducted across Kaiser Permanente Northern California (KPNC) and Mid Atlantic States (KPMAS) during the 2024-2025 influenza season. Unvaccinated adults aged >18 years and able to be contacted via health system-based secure messaging or email were included. Eligible participants were randomized at KPNC and KPMAS in a 1:1:1:1 fashion to 4 study arms, corresponding to messaging type (CV-focused communication or usual care communication) at two sequential touchpoints (initial letter and subsequent reminder letter). The primary outcome was receipt of influenza vaccination on or before January 1, 2025. There were 6 coprimary comparisons to estimate the effects of nudging content and timing: (1) Arms 1, 2, and 3 vs Arm 4 (CV nudge vs usual care; three comparisons), (2) Arm 1 vs Arm 2 (two vs one round of CV nudging), (3) Arm 2 vs Arm 3 (early vs late CV nudging), and (4) pooled Arms 1 to 3 vs Arm 4 (any CV nudge vs usual care). A prespecified secondary outcome was time to vaccination. Exploratory outcomes included major adverse CV events and all-cause death.
Results: A total of 3,668,428 members were randomized (3,234,745 from KPNC, 433,683 from KPMAS). Randomized participants had a mean (SD) age of 48.3 (18.2) years, 1,939,380 (52.9%) were female, 386,33 (10.5%) were Black, 791,658 (21.6%) were Asian and Native Hawaiian/Pacific Islander. Hispanic ethnicity was documented in 774,790 (21.1%) of participants. The vaccination rate using available documentation in the prior 2023-2024 influenza season was 38.8%. Presence of cardiometabolic comorbidities including heart failure, diabetes, and hypertension approximated that of US adult population. Primary and key secondary outcomes will be ascertained from electronic health records and linked data sources through January 1, 2025. Exploratory outcomes will be assessed through August 31, 2025. Implementation outcomes (read receipts, email hyperlink click-throughs) will also be assessed in an exploratory fashion.
Conclusions: KP-VACCINATE is one of the largest clinical trials conduted to date, enrolling more than 3.6 million adults, and uniquely embedded in a integrated healthcare delivery system. It will evaluate the effectiveness and optimal timing of CV-focused vs usual care messaging in increasing influenza vaccination through standard health system outreach across a diverse US population. Findings will inform future public health messaging and demonstrate large-scale, pragmatic randomization within learning healthcare systems.
Trial registration: Clinicaltrials.gov: NCT06571747.
Copyright © 2025 Elsevier Inc. All rights reserved.