Time of day for vaccination, outcomes, and relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine: A post hoc analysis of the DANFLU-1 randomized clinical trial

J Infect. 2024 Nov;89(5):106276. doi: 10.1016/j.jinf.2024.106276. Epub 2024 Sep 18.

Abstract

Objectives: Morning influenza vaccination enhances antibody response. In this post hoc analysis of the DANFLU-1 trial, we sought to evaluate the association between time of day for vaccination (ToV) and outcomes and whether ToV modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine.

Methods: DANFLU-1 was a pragmatic feasibility trial of QIV-HD vs. QIV-SD. Outcomes included hospitalizations and mortality. For subgroup analysis, the population was dichotomized at median ToV into two groups (early and late).

Results: The study population included 12,477 participants. Mean age was 71.7 ± 3.9 years with 5877 (47.1%) female participants. Median ToV was 11.29 AM. Earlier ToV was associated with fewer respiratory hospitalizations independent of vaccine type, which persisted in adjusted analysis (IRR 0.88 per 1-hour decrement (95% CI 0.78- 0.98, p = 0.025). No effect modification by continuous or dichotomous ToV was found. In subgroup analysis, effects consistently favored QIV-HD against hospitalizations for pneumonia or influenza (early: IRR 0.30; late: 0.29), all-cause hospitalizations (early: IRR 0.87; late: 0.86), and mortality (early: HR 0.53; late: 0.50).

Conclusion: In this exploratory post hoc analysis, earlier ToV was associated with fewer respiratory hospitalizations. The relative effectiveness of QIV-HD vs. QIV-SD was not modified by ToV. Further research is needed to confirm findings.

Trial registration: Clinicaltrials.gov: NCT05048589.

Keywords: Health care; Human; Influenza; Outcome assessment; Pragmatic clinical trial; Vaccination.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Female
  • Hospitalization* / statistics & numerical data
  • Humans
  • Immunization Schedule
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / immunology
  • Influenza, Human* / prevention & control
  • Male
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • Vaccination*
  • Vaccine Efficacy

Substances

  • Influenza Vaccines

Associated data

  • ClinicalTrials.gov/NCT05048589