A pragmatic randomized feasibility trial of influenza vaccines

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

Journal article

A pragmatic randomized feasibility trial of influenza vaccines

Abstract:: 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; ClinicalTrials.gov number, NCT05048589.)

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Johansen, N. D., Modin, D., Nealon, J., Samson, S., Salamand, C., Loiacono, M. M., Larsen, C. S., Jensen, A. M. R., Landler, N. E., Claggett, B. L., Solomon, S. D., Landray, M. J., Gislason, G. H., Køber, L., Jensen, J. U. S., Sivapalan, P., Vestergaard, L. S., Valentiner-Branth, P., Krause, T. G., & Biering-Sørensen, T. (2023). A pragmatic randomized feasibility trial of influenza vaccines. NEJM Evidence, 2(2).

MLA Style

Johansen, N. D., et al. “A Pragmatic Randomized Feasibility Trial of Influenza Vaccines.” NEJM Evidence, vol. 2, no. 2, Massachusetts Medical Society, 2023.

Chicago Style

Johansen, ND, D Modin, J Nealon, S Samson, C Salamand, MM Loiacono, CS Larsen, et al. 2023. “A Pragmatic Randomized Feasibility Trial of Influenza Vaccines.” NEJM Evidence 2 (2).
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