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InfluenzaPhase 4DANFLU-2NCT05517174

A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults

A Phase 4 study testing High-Dose Quadrivalent Influenza Vaccine and Standard-Dose Quadrivalent Influenza Vaccine in people with Influenza, run by Tor Biering-Sørensen at 2 sites in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this pragmatic randomized trial is to evaluate the relative vaccine effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) vs. standard-dose quadrivalent influenza vaccine (QIV-SD) in older adults. Participants will be randomized 1:1 to either QIV-HD or QIV-SD. Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
Conditions the study is for
Influenza
What is being tested?
High-Dose Quadrivalent Influenza Vaccine and Standard-Dose Quadrivalent Influenza Vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
332,438 participants
Where
2 sitesDenmark
Study dates
22 Sep 2022to 31 Aug 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Age 65 years and above (this inclusion criterion will be modified according to the Danish government's official recommendations for the 2022/2023 and 2023/2024 influenza seasons)
  • Informed consent form has been signed and dated

Who cannot join

  • There are no specific exclusion criteria for this study

Trial locations and contacts

2 sites in 1 country.

Denmark2 sites

  • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

    Hellerup, Capital Region, 2900

  • Danske Lægers Vaccinations Service

    Søborg, 2860

Other trials in Denmark

About this study

The purpose of this pragmatic randomized trial is to evaluate the relative vaccine effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) vs. standard-dose quadrivalent influenza vaccine (QIV-SD) in older adults. Participants will be randomized 1:1 to either QIV-HD or QIV-SD.

Read the detailed description

The study is a pragmatic, registry-based, open-label, active-controlled, individually randomized trial. The Danish nationwide administrative health registries will be used for data collection including baseline information, follow-up data, and safety monitoring. The study aims to randomize 339,700 participants over 3 influenza seasons. In each season, participants will be individually randomized 1:1 to receive either QIV-HD or QIV-SD. During the 2023/2024 and 2024/2025 seasons, up to 12,000 participants will be enrolled in a sub-cohort where participants are asked to perform home self-swabs and answer symptom questionnaires in case of influenza-like illness to enable further assessment of the impact of QIV-HD vs. QIV-SD on patient-reported outcomes among individuals with influenza-like illness and laboratory-confirmed influenza.

Conditions
Influenza
Being tested
High-Dose Quadrivalent Influenza Vaccine, Standard-Dose Quadrivalent Influenza Vaccine
Keywords
Influenza, Vaccination, Pragmatic, Registry, Pneumonia, Respiratory, Cardiovascular
Medical subject headings
Influenza, Human, Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High-Dose Quadrivalent Influenza VaccineBiological

    Also called QIV-HD

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

  • Standard-Dose Quadrivalent Influenza VaccineBiological

    Also called QIV-SD

    Any standard-dose quadrivalent influenza vaccine administered in the Danish governmental influenza vaccine program may be used.

Study groups in NCT05517174
Study groupRoleWhat they receive
High-Dose Quadrivalent Influenza VaccineExperimentalQIV-HD single injection at Day 0
Receives: Biological: High-Dose Quadrivalent Influenza Vaccine
Standard-Dose Quadrivalent Influenza VaccineActive comparatorQIV-SD single injection at Day 0
Receives: Biological: Standard-Dose Quadrivalent Influenza Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hospitalization for influenza or pneumonia

    Measured: ≥14 days after vaccination up to 8 months

Secondary outcomes (5)

  1. Hospitalization for any cardio-respiratory disease

    Measured: ≥14 days after vaccination up to 8 months

  2. All-cause hospitalization

    Measured: ≥14 days after vaccination up to 8 months

  3. All-cause mortality

    Measured: ≥14 days after vaccination up to 8 months

  4. Hospitalization for influenza

    Measured: ≥14 days after vaccination up to 8 months

  5. Hospitalization for pneumonia

    Measured: ≥14 days after vaccination up to 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2022
  2. Study start22 Sep 2022
  3. Primary completion31 May 2025
  4. Study completion31 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
332,438 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05517174
Sponsor's protocol ID
DANFLU-2
Other IDs
2022-500657-17-00
Acronym
DANFLU-2
Status last verified
Sep 2025
First submitted
20 Aug 2022
Last updated
12 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: In this trial, baseline and endpoint data will be collected from Danish administrative health registries, which are subject to Danish legislation and can only be made available to a third party under certain conditions. Please contact the sponsor-investigator in case of any inquiries.

Publications

  • Nielsen AB, Johansen ND, Modin D, Loiacono MM, Harris RC, Dufournet M, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Claggett BL, Janstrup KH, Bartholdy KV, Bernholm KF, Borchsenius JIH, Davidovski FS, Davodian LW, Dons M, Duus LS, Espersen C, Fussing FH, Jensen AMR, Landler NE, Langhoff ACF, Lassen MCH, Ottosen CI, Sengelov M, Skaarup KG, Pareek M, Muller-Wieland D, Solomon SD, Landray MJ, Gislason GH, Kober L, Sivapalan P, Martel CJ, Jensen JUS, Biering-Sorensen T. High-Dose vs Standard-Dose Influenza Vaccine in Older Adults With Diabetes: A Secondary Analysis of the DANFLU-2 Randomized Clinical Trial. JAMA Intern Med. 2026 Mar 1;186(3):311-320. doi: 10.1001/jamainternmed.2025.7286.

    PubMed 41525066

  • Johansen ND, Modin D, Loiacono MM, Harris RC, Dufournet M, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Claggett BL, Janstrup KH, Bartholdy KV, Bernholm KF, Borchsenius JIH, Davidovski FS, Davodian LW, Dons M, Duus LS, Espersen C, Fussing FH, Jensen AMR, Landler NE, Langhoff ACF, Lassen MCH, Nielsen AB, Ottosen CI, Sengelov M, Skaarup KG, Solomon SD, Landray MJ, Gislason GH, Kober L, Ralfkiaer L, Nealon J, Sivapalan P, Martel CJ, Jensen JUS, Biering-Sorensen T. High-Dose Influenza Vaccine Effectiveness against Hospitalization in Older Adults. N Engl J Med. 2025 Dec 11;393(23):2291-2302. doi: 10.1056/NEJMoa2509907. Epub 2025 Aug 30.

    PubMed 40888720

  • Johansen ND, Modin D, Loiacono MM, Harris RC, Dufournet M, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Claggett BL, Janstrup KH, Bartholdy KV, Bernholm KF, Borchsenius JIH, Davidovski FS, Davodian LW, Dons M, Duus LS, Espersen C, Fussing FH, Jensen AMR, Landler NE, Langhoff ACF, Lassen MCH, Nielsen AB, Ottosen CI, Sengelov M, Skaarup KG, Pareek M, Solomon SD, Landray MJ, Gislason GH, Kober L, Sivapalan P, Martel CJ, Jensen JUS, Biering-Sorensen T. High-Dose vs Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: A Prespecified Secondary Analysis of the DANFLU-2 Randomized Clinical Trial. JAMA Cardiol. 2025 Nov 1;10(11):1186-1194. doi: 10.1001/jamacardio.2025.3460.

    PubMed 40884442

  • Skaarup KG, Johansen ND, Modin D, Loiacono MM, Harris RC, Dufournet M, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Claggett BL, Bartholdy KV, Bernholm KF, Borchsenius JIH, Davidovski FS, Davodian LW, Dons M, Duus LS, Espersen C, Fussing FH, Jensen AMR, Landler NE, Langhoff ACF, Lassen MCH, Nielsen AB, Ottosen CI, Sengelov M, Solomon SD, Landray MJ, Gislason GH, Kober L, Sivapalan P, Martel CJ, Jensen JUS, Mebazaa A, Biering-Sorensen T. High-Dose Versus Standard-Dose Influenza Vaccine in Heart Failure: A Prespecified Analysis of the DANFLU-2 Trial. Circ Heart Fail. 2025 Nov;18(11):e013678. doi: 10.1161/CIRCHEARTFAILURE.125.013678. Epub 2025 Aug 30.

    PubMed 40884411

  • Davidovski FS, Skaarup KG, Johansen ND, Modin D, Shaikh N, Bartelt-Hofer J, Loiacono MM, Harris RC, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Jessen R, Steenhard N, Claggett BL, Solomon SD, Kober L, Sivapalan P, Jensen JUS, Martel CJ, Biering-Sorensen T. Patient-reported outcomes and home-based self-swabs for influenza-like illness events - lessons learned from the 2023/2024 DANFLU-2 Homeswab PRO substudy. J Patient Rep Outcomes. 2025 Aug 22;9(1):108. doi: 10.1186/s41687-025-00936-8.

    PubMed 40844659

  • Johansen ND, Modin D, Loiacono MM, Harris RC, Dufournet M, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Claggett BL, Skaarup KG, Davidovski FS, Solomon SD, Landray MJ, Gislason GH, Kober L, Sivapalan P, Martel CJ, Jensen JUS, Biering-Sorensen T. 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. Am Heart J. 2026 Jan;291:186-198. doi: 10.1016/j.ahj.2025.07.069. Epub 2025 Jul 30.

    PubMed 40749884

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing High-Dose Quadrivalent Influenza Vaccine and Standard-Dose Quadrivalent Influenza Vaccine in people with Influenza, run by Tor Biering-Sørensen at 2 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hospitalization for influenza or pneumonia (time frame: ≥14 days after vaccination up to 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05517174, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.

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