tetano
Editor, Senior Moderator
Am Heart J
. 2025 Jul 30:S0002-8703(25)00287-X.
doi: 10.1016/j.ahj.2025.07.069. Online ahead of print. A Pragmatic Individually Randomized Trial to Evaluate the Effectiveness of High-Dose vs. Standard-Dose Influenza Vaccine in Older Adults: Rationale and Design of the DANFLU-2 Trial
Niklas Dyrby Johansen[SUP] 1 [/SUP], Daniel Modin[SUP] 1 [/SUP], Matthew M Loiacono[SUP] 2 [/SUP], Rebecca C Harris[SUP] 3 [/SUP], Marine Dufournet[SUP] 4 [/SUP], Carsten Schade Larsen[SUP] 5 [/SUP], Lykke Larsen[SUP] 6 [/SUP], Lothar Wiese[SUP] 7 [/SUP], Michael Dalager-Pedersen[SUP] 8 [/SUP], Brian L Claggett[SUP] 9 [/SUP], Kristoffer Grundtvig Skaarup[SUP] 1 [/SUP], Filip Søskov Davidovski[SUP] 1 [/SUP], Scott D Solomon[SUP] 9 [/SUP], Martin J Landray[SUP] 10 [/SUP], Gunnar H Gislason[SUP] 11 [/SUP], Lars Køber[SUP] 12 [/SUP], Pradeesh Sivapalan[SUP] 13 [/SUP], Cyril Jean-Marie Martel[SUP] 14 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 13 [/SUP], Tor Biering-Sørensen[SUP] 15 [/SUP]
Affiliations
Background: The high-dose inactivated influenza vaccine (HD-IIV) has been shown to reduce the incidence of influenza infection compared with standard-dose inactivated influenza vaccine (SD-IIV); however, its effectiveness in preventing severe respiratory and cardiovascular outcomes in the older general population has not yet been assessed in a fully powered individually randomized trial.
Methods: DANFLU-2 is an ongoing pragmatic, registry-based, open-label, active-controlled, individually randomized trial conducted in Denmark during the 2022/2023, 2023/2024, and 2024/2025 influenza seasons. Utilizing innovative electronic recruitment strategies and an online informed consent process, the trial has enrolled 332,438 older adults ≥65 years; enrollment was completed in October 2024. Participants were randomly allocated in a 1:1 ratio to either HD-IIV or SD-IIV. Baseline, endpoint, and safety data are primarily obtained from the nationwide Danish administrative health registries. The primary endpoint is hospitalization for influenza or pneumonia with the trial also powered to assess the 1[SUP]st[/SUP] secondary endpoint of hospitalization for any cardio-respiratory disease. The additional secondary endpoints of all-cause hospitalization and mortality will be tested hierarchically. Key ancillary analyses include cost-effectiveness and health care resource consumption assessments as well as a home self-swab sub-cohort.
Discussion: DANFLU-2 is the largest individually randomized influenza vaccine trial ever conducted and will provide critical, high-quality evidence on the effectiveness of HD-IIV against cardio-respiratory hospitalizations and mortality in the older general population.
Trial registration: Clinicaltrials.gov: NCT05517174, registered August 24, 2022, https://clinicaltrials.gov/study/NCT05517174.
Keywords: Randomized controlled trial; high-dose; influenza; pragmatic; registry; vaccination.
. 2025 Jul 30:S0002-8703(25)00287-X.
doi: 10.1016/j.ahj.2025.07.069. Online ahead of print. A Pragmatic Individually Randomized Trial to Evaluate the Effectiveness of High-Dose vs. Standard-Dose Influenza Vaccine in Older Adults: Rationale and Design of the DANFLU-2 Trial
Niklas Dyrby Johansen[SUP] 1 [/SUP], Daniel Modin[SUP] 1 [/SUP], Matthew M Loiacono[SUP] 2 [/SUP], Rebecca C Harris[SUP] 3 [/SUP], Marine Dufournet[SUP] 4 [/SUP], Carsten Schade Larsen[SUP] 5 [/SUP], Lykke Larsen[SUP] 6 [/SUP], Lothar Wiese[SUP] 7 [/SUP], Michael Dalager-Pedersen[SUP] 8 [/SUP], Brian L Claggett[SUP] 9 [/SUP], Kristoffer Grundtvig Skaarup[SUP] 1 [/SUP], Filip Søskov Davidovski[SUP] 1 [/SUP], Scott D Solomon[SUP] 9 [/SUP], Martin J Landray[SUP] 10 [/SUP], Gunnar H Gislason[SUP] 11 [/SUP], Lars Køber[SUP] 12 [/SUP], Pradeesh Sivapalan[SUP] 13 [/SUP], Cyril Jean-Marie Martel[SUP] 14 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 13 [/SUP], Tor Biering-Sørensen[SUP] 15 [/SUP]
Affiliations
- PMID: 40749884
- DOI: 10.1016/j.ahj.2025.07.069
Background: The high-dose inactivated influenza vaccine (HD-IIV) has been shown to reduce the incidence of influenza infection compared with standard-dose inactivated influenza vaccine (SD-IIV); however, its effectiveness in preventing severe respiratory and cardiovascular outcomes in the older general population has not yet been assessed in a fully powered individually randomized trial.
Methods: DANFLU-2 is an ongoing pragmatic, registry-based, open-label, active-controlled, individually randomized trial conducted in Denmark during the 2022/2023, 2023/2024, and 2024/2025 influenza seasons. Utilizing innovative electronic recruitment strategies and an online informed consent process, the trial has enrolled 332,438 older adults ≥65 years; enrollment was completed in October 2024. Participants were randomly allocated in a 1:1 ratio to either HD-IIV or SD-IIV. Baseline, endpoint, and safety data are primarily obtained from the nationwide Danish administrative health registries. The primary endpoint is hospitalization for influenza or pneumonia with the trial also powered to assess the 1[SUP]st[/SUP] secondary endpoint of hospitalization for any cardio-respiratory disease. The additional secondary endpoints of all-cause hospitalization and mortality will be tested hierarchically. Key ancillary analyses include cost-effectiveness and health care resource consumption assessments as well as a home self-swab sub-cohort.
Discussion: DANFLU-2 is the largest individually randomized influenza vaccine trial ever conducted and will provide critical, high-quality evidence on the effectiveness of HD-IIV against cardio-respiratory hospitalizations and mortality in the older general population.
Trial registration: Clinicaltrials.gov: NCT05517174, registered August 24, 2022, https://clinicaltrials.gov/study/NCT05517174.
Keywords: Randomized controlled trial; high-dose; influenza; pragmatic; registry; vaccination.