Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting (DANFLU-1)

Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting

Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting

The purpose of the study is to assess the feasibility of identifying, recruiting and randomizing a large sample of Danish citizens aged 65-79 years to high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine in the 2021/2022 influenza season in a registry-based setting using Danish nationwide registries for all data collection including baseline information and outcome assessment.

To evaluate the feasibility of recruiting and randomizing Danish citizens aged 65-79 years, we aim to randomize 40,000 citizens 1:1 to high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine in a pragmatic, open-label, registry-based design using the infrastructure of Danske Lægers Vaccinations Service (DLVS), an organization responsible for numerous vaccination clinics in Denmark, for recruitment and randomization and Danish nationwide registries for data collection. Citizens will be recruited by DLVS and randomized and vaccinated at the DLVS clinics. All collection of data related to baseline information, outcomes, and safety monitoring will be performed by a central trial site utilizing information from Danish nationwide health registries. The findings of this pilot trial will indicate whether the conduction of a full-scale, adequately powered pragmatic RCT is feasible within the Danish registry-based framework.

For the control arm, the standard-dose quadrivalent influenza vaccines Influvactetra® and Vaxigriptetra will be used.

For the control arm, the high-dose quadrivalent influenza vaccine Efluelda®/Fluzone® High-Dose Quadrivalent will be used.

Comparison of baseline characteristics for the QIV-HD and QIV-SD groups to the overall Danish general population aged 65-79 years

Comparison of baseline characteristics for the QIV-HD and QIV-SD groups to the population aged 65-79 years in the DLVS database used for recruitment

Description of event rates and calculation of relative vaccine effectiveness for hospitalization for influenza and/or pneumonia

First hospitalization with a primary (A) diagnosis code for influenza or pneumonia of at least 1 night duration

Description of event rates and calculation of relative vaccine effectiveness for hospitalization for respiratory disease

First hospitalization with a primary (A) diagnosis code for respiratory disease of at least 1 night duration

Description of event rates and calculation of relative vaccine effectiveness for hospitalization for cardio-respiratory disease

First hospitalization with a primary (A) diagnosis code for cardio-respiratory disease of at least 1 night duration

Description of event rates and calculation of relative vaccine effectiveness for hospitalization for cardiovascular disease

First hospitalization with a primary (A) diagnosis code for cardiovascular disease of at least 1 night duration

Description of event rates and calculation of relative vaccine effectiveness for hospitalization from any cause

Description of event rates and calculation of relative vaccine effectiveness for hospitalization for COVID-19

Inclusion Criteria: Age 65-79 years Informed consent form has been signed and dated Exclusion Criteria: 1. Allergy/hypersensitivity towards the influenza vaccines used in this study

Cardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology, Herlev and Gentofte Hospital

Sharing of individual-level data stemming from Danish administrative registries is illegal according to Danish law.

Johansen ND, Modin D, Nealon J, Samson S, Salamand C, Larsen CS, Claggett BL, Solomon SD, Landray MJ, Gislason GH, Kober L, Jensen JUS, Sivapalan P, Vestergaard LS, Valentiner-Branth P, Krause TG, Biering-Sorensen T. Feasibility of randomizing Danish citizens aged 65-79 years to high-dose quadrivalent influenza vaccine vs. standard-dose quadrivalent influenza vaccine in a pragmatic registry-based setting: rationale and design of the DANFLU-1 Trial. Pilot Feasibility Stud. 2022 Apr 21;8(1):87. doi: 10.1186/s40814-022-01044-w.