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A pragmatic randomized feasibility trial of influenza vaccines

Title: A pragmatic randomized feasibility trial of influenza vaccines
Authors: Johansen, ND; Modin, D; Nealon, J; Samson, S; Salamand, C; Loiacono, MM; Larsen, CS; Jensen, AMR; Landler, NE; Claggett, BL; Solomon, SD; Landray, MJ; Gislason, GH; Køber, L; Jensen, JUS; Sivapalan, P; Vestergaard, LS; Valentiner-Branth, P; Krause, TG; Biering-Sørensen, T
Publisher Information: Massachusetts Medical Society
Publication Year: 2023
Collection: Oxford University Research Archive (ORA)
Description: Background: The relative vaccine effectiveness (rVE) of high-dose quadrivalent influenza vaccines (QIV-HD) versus standard-dose quadrivalent influenza vaccines (QIV-SD) against hospitalizations and mortality in the general older population has not been evaluated in an individually randomized trial. Because of the large sample size required, such a trial will need to incorporate innovative, pragmatic elements. Methods: We conducted a pragmatic, open-label, active-controlled, randomized feasibility trial in Danish citizens aged 65 to 79 years during the 2021–2022 influenza season. Participants were randomly assigned 1:1 to receive QIV-HD or QIV-SD. Randomization was integrated into routine vaccination practice, and the trial relied solely on nationwide administrative health registries for data collection. Outcomes consisted of a feasibility assessment and descriptive rVE estimates. Results: We invited 34,000 persons to participate. A total of 12,477 randomly assigned participants were included in the final analyses. Mean (±SD) age was 71.7±3.9 years, and 5877 (47.1%) were women. Registry-based data collection was feasible, with complete follow-up data for 99.9% of participants. Baseline characteristics were comparable to those of the overall Danish population aged 65 to 79 years. The incidence of hospitalization for influenza or pneumonia was 10 (0.2%) of 6245 in the QIV-HD group and 28 (0.4%) of 6232 in the QIV-SD group (rVE, 64.4%; 95% confidence interval, 24.4 to 84.6). All-cause death occurred in 21 (0.3%) and 41 (0.7%) participants in the QIV-HD and QIV-SD groups, respectively (rVE, 48.9%; 95% confidence interval, 11.5 to 71.3). Conclusions: Conducting a pragmatic randomized trial of QIV-HD versus QIV-SD using existing infrastructure and registry-based data collection was feasible. The findings of lower incidence of hospitalization for influenza or pneumonia and all-cause mortality in the QIV-HD group compared with the QIV-SD group require replication in a future, fully powered trial. (Funded by Sanofi; ...
Document Type: article in journal/newspaper
Language: English
Relation: https://doi.org/10.1056/evidoa2200206
DOI: 10.1056/evidoa2200206
Availability: https://doi.org/10.1056/evidoa2200206; https://ora.ox.ac.uk/objects/uuid:5c283b0f-f28f-4b3e-bb87-3073033299df
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.90798227
Database: BASE