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InfluenzaPhase 2DANFLU-1NCT05048589

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

A Phase 2 study testing Standard-Dose Quadrivalent Influenza Vaccine and High-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 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… Read more about this study

Who is it for?
Ages 65 to 79 yearsHealthy volunteers can take part
Conditions the study is for
Influenza
What is being tested?
Standard-Dose Quadrivalent Influenza Vaccine and High-Dose Quadrivalent Influenza Vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12,551 participants
Where
2 sitesDenmark
Study dates
1 Oct 2021to 31 May 2022
Phase
Phase 2
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 to 79 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

Denmark2 sites

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

    Hellerup, 2900

  • Danske Lægers Vaccinations Service

    Søborg, 2860

Other trials in Denmark

About this study

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.

Read the detailed description

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.

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

What participants receive

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

  • Standard-Dose Quadrivalent Influenza VaccineDrug

    Also called QIV-SD

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

  • High-Dose Quadrivalent Influenza VaccineDrug

    Also called QIV-HD

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

Study groups in NCT05048589
Study groupRoleWhat they receive
Standard-Dose Quadrivalent Influenza VaccineActive comparatorQIV-SD single injection at Day 0
Receives: Drug: Standard-Dose Quadrivalent Influenza Vaccine
High-Dose Quadrivalent Influenza VaccineExperimentalQIV-HD single injection at Day 0
Receives: Drug: High-Dose Quadrivalent Influenza Vaccine

What is being measured

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

  1. Number of persons contacted by recruitment letter

    Measured: Up to 8 months

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

    Measured: Up to 8 months

  3. Agreement between randomization assignment and actual received vaccine

    Measured: Up to 8 months

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

    Measured: Up to 8 months

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

    Measured: Up to 8 months

  6. 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

    Measured: Up to 8 months

  7. 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

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

  8. 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

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

  9. 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

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

  10. 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

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

  11. 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

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

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

    Death from any cause

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

  13. 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

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

Timeline

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

  1. First posted17 Sep 2021
  2. Study start1 Oct 2021
  3. Primary completion31 May 2022
  4. Study completion31 May 2022

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
12,551 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05048589
Sponsor's protocol ID
DANFLU-1
Other IDs
QHD00027, 2021-003170-31
Acronym
DANFLU-1
Status last verified
Aug 2022
First submitted
31 Aug 2021
Last updated
23 Aug 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Sharing of individual-level data stemming from Danish administrative registries is illegal according to Danish law.

Publications

  • Christensen J, Johansen ND, Bernholm KF, Borchsenius JIH, Janstrup KH, Modin D, Skaarup KG, Nealon J, Samson S, Loiacono M, Huang Y, 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. Positive predictive value of respiratory infection diagnoses in the Danish National Patient Registry: A post hoc validation analysis of the DANFLU-1 trial. Int J Infect Dis. 2026 Jul;168:108703. doi: 10.1016/j.ijid.2026.108703. Epub 2026 Apr 13.

    PubMed 41985620

  • 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.

    PubMed 41238377

  • 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.

    PubMed 41177098

  • 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.

    PubMed 39303788

  • 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.

    PubMed 39215646

  • Lassen MCH, Johansen ND, Modin D, Nealon J, Samson S, Dufournet M, Loiacono MM, Larsen CS, Jensen AMR, Landler NE, Claggett BL, Solomon SD, Landray MJ, Gislason GH, Kober L, Jensen JUS, Sivapalan P, Vestergaard LS, Krause TG, Biering-Sorensen T. Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: A post-hoc analysis of the DANFLU-1 trial. Diabetes Obes Metab. 2024 May;26(5):1821-1829. doi: 10.1111/dom.15498.

    PubMed 38586966

  • 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.

    PubMed 38320035

  • 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.

    PubMed 38286177

  • 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.

    PubMed 35449028

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard-Dose Quadrivalent Influenza Vaccine and High-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 23 Aug 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Number of persons contacted by recruitment letter (time frame: Up to 8 months). The study lists 13 primary outcomes in all. 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 NCT05048589, which also lists 9 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 23 Aug 2022.

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