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

NCT05048589 | Completed Phase 2

• 3 other identifiers: DANFLU-1QHD000272021-003170-31
• Study Type: interventional
• Target: 12,551
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Influenza

Keywords

Influenza; Vaccination; Pragmatic; Registry

Outcome Measures

Primary Outcomes (13)

• Number of persons contacted by recruitment letter

  Up to 8 months

• Number of participants included and randomized to QIV-HD or QIV-SD

  Up to 8 months

• Agreement between randomization assignment and actual received vaccine

  Up to 8 months

• Balance between groups in terms of number of subjects in each arm and baseline characteristics

  Up to 8 months

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

  Up to 8 months

• 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

  Up to 8 months

• 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

  >= 14 days after vaccination up to 8 months post-vaccination

• 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

  >= 14 days after vaccination up to 8 months post-vaccination

• 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

  >= 14 days after vaccination up to 8 months post-vaccination

• 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

  >= 14 days after vaccination up to 8 months post-vaccination

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

  First hospitalization with any diagnosis code of at least 1 night duration

  >= 14 days after vaccination up to 8 months post-vaccination

• Description of event rates and calculation of relative vaccine effectiveness for all-cause mortality

  Death from any cause

  >= 14 days after vaccination up to 8 months post-vaccination

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

  First hospitalization with a primary (A) diagnosis code for COVID-19 of at least 1 night duration

  >= 14 days after vaccination up to 8 months post-vaccination

Study Arms (2)

Standard-Dose Quadrivalent Influenza Vaccine

ACTIVE COMPARATOR

QIV-SD single injection at Day 0

Drug: Standard-Dose Quadrivalent Influenza Vaccine

High-Dose Quadrivalent Influenza Vaccine

EXPERIMENTAL

QIV-HD single injection at Day 0

Drug: High-Dose Quadrivalent Influenza Vaccine

Interventions

Standard-Dose Quadrivalent Influenza Vaccine DRUG

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

Also known as: QIV-SD

Standard-Dose Quadrivalent Influenza Vaccine

High-Dose Quadrivalent Influenza Vaccine DRUG

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

Also known as: QIV-HD

High-Dose Quadrivalent Influenza Vaccine

Eligibility Criteria

• Age: 65 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65-79 years
• Informed consent form has been signed and dated

You may not qualify if:

• \. Allergy/hypersensitivity towards the influenza vaccines used in this study

Sponsors & Collaborators

• Tor Biering-Sørensen: lead
• Sanofi Pasteur, a Sanofi Company: collaborator

Study Sites (2)

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

Hellerup, 2900, Denmark

Location

Danske Lægers Vaccinations Service

Søborg, 2860, Denmark

Location

Related Publications (7)

• Langhoff AF, Johansen ND, Modin D, Janstrup KH, Bartholdy KV, Espersen C, Nealon J, Samson S, Loiacono MM, Harris R, Larsen CS, Jensen AMR, Landler NE, Claggett BL, Solomon SD, Landray MJ, Gislason GH, Kober L, Sivapalan P, Jensen JUS, Biering-Sorensen T. High-Dose vs. Standard-Dose Influenza Vaccine in Older Patients With Hypertension: A Post Hoc Analysis of DANFLU-1. J Clin Hypertens (Greenwich). 2025 Nov;27(11):e70177. doi: 10.1111/jch.70177.

  PMID: 41238377 DERIVED

• Duus LS, Johansen ND, Modin D, Janstrup KH, Nealon J, Samson S, Loiacono MM, Harris RC, Larsen CS, Reimer Jensen AM, Claggett BL, Solomon SD, Landray MJ, Gislason GH, Kober L, Sivapalan P, Staehr Jensen JU, Biering-Sorensen T. Effects of high-dose versus standard-dose influenza vaccine among patients with chronic lung disease: A prespecified analysis of the DANFLU-1 trial. Respir Investig. 2025 Nov;63(6):1309-1315. doi: 10.1016/j.resinv.2025.10.016. Epub 2025 Nov 1.

  PMID: 41177098 DERIVED

• Christensen J, Johansen ND, Janstrup KH, Modin D, Skaarup KG, Nealon J, Samson S, Loiacono M, Harris R, Larsen CS, Jensen AMR, Landler NE, Claggett BL, Solomon SD, Gislason GH, Kober L, Landray MJ, Sivapalan P, Jensen JUS, Biering-Sorensen T. 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.

  PMID: 39303788 DERIVED

• Christensen J, Johansen ND, Modin D, Janstrup KH, Nealon J, Samson S, Loiacono M, Harris R, Larsen CS, Jensen AMR, Landler NE, Claggett BL, Solomon SD, Gislason GH, Kober L, Landray MJ, Sivapalan P, Jensen JUS, Biering-Sorensen T. Relative Effectiveness of High-Dose Versus Standard-Dose Quadrivalent Influenza Vaccine in Older Adults With Cardiovascular Disease: A Prespecified Analysis of the DANFLU-1 Randomized Clinical Trial. Circ Cardiovasc Qual Outcomes. 2025 Feb;18(2):e011496. doi: 10.1161/CIRCOUTCOMES.124.011496. Epub 2024 Aug 31.

  PMID: 39215646 DERIVED

• 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, Kober L, Jensen JUS, Sivapalan P, Vestergaard LS, Valentiner-Branth P, Krause TG, Biering-Sorensen T. A Pragmatic Randomized Feasibility Trial of Influenza Vaccines. NEJM Evid. 2023 Feb;2(2):EVIDoa2200206. doi: 10.1056/EVIDoa2200206. Epub 2023 Jan 23.

  PMID: 38320035 DERIVED

• Johansen ND, Modin D, Skaarup KG, Nealon J, Samson S, Dufournet M, Loiacono MM, Harris RC, Larsen CS, Jensen AMR, Landler NE, Claggett BL, Solomon SD, Landray MJ, Gislason GH, Kober L, Jensen JUS, Sivapalan P, Vestergaard LS, Valentiner-Branth P, Krause TG, Biering-Sorensen T. Effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against recurrent hospitalizations and mortality in relation to influenza circulation: A post-hoc analysis of the DANFLU-1 randomized clinical trial. Clin Microbiol Infect. 2024 Nov;30(11):1453-1459. doi: 10.1016/j.cmi.2024.01.017. Epub 2024 Jan 28.

  PMID: 38286177 DERIVED

• 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.

  PMID: 35449028 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Tor Biering-Sørensen, MD, PhD, MPH

  Research Director

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Director, MD, PhD, MPH

Study Record Dates

• First Submitted: August 31, 2021
• First Posted: September 17, 2021
• Study Start: October 1, 2021
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: August 23, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)