NCT05517174

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
332,438

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Sep 2022

Typical duration for phase_4

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 20, 2022

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 26, 2022

Completed
27 days until next milestone

Study Start

First participant enrolled

September 22, 2022

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2025

Completed
Last Updated

September 12, 2025

Status Verified

September 1, 2025

Enrollment Period

2.7 years

First QC Date

August 20, 2022

Last Update Submit

September 8, 2025

Conditions

Influenza

Keywords

InfluenzaVaccinationPragmaticRegistryPneumoniaRespiratoryCardiovascular

Outcome Measures

Primary Outcomes (1)

  • Hospitalization for influenza or pneumonia

    ≥14 days after vaccination up to 8 months

Secondary Outcomes (5)

  • Hospitalization for any cardio-respiratory disease

    ≥14 days after vaccination up to 8 months

  • All-cause hospitalization

    ≥14 days after vaccination up to 8 months

  • All-cause mortality

    ≥14 days after vaccination up to 8 months

  • Hospitalization for influenza

    ≥14 days after vaccination up to 8 months

  • Hospitalization for pneumonia

    ≥14 days after vaccination up to 8 months

Other Outcomes (36)

  • Hospitalization for influenza or pneumonia (alternate definition)

    ≥14 days after vaccination up to 8 months

  • Hospitalization for pneumonia (alternate definition)

    ≥14 days after vaccination up to 8 months

  • Hospitalization for influenza (alternate definition)

    ≥14 days after vaccination up to 8 months

  • +33 more other outcomes

Study Arms (2)

High-Dose Quadrivalent Influenza Vaccine

EXPERIMENTAL

QIV-HD single injection at Day 0

Biological: High-Dose Quadrivalent Influenza Vaccine

Standard-Dose Quadrivalent Influenza Vaccine

ACTIVE COMPARATOR

QIV-SD single injection at Day 0

Biological: Standard-Dose Quadrivalent Influenza Vaccine

Interventions

High-Dose Quadrivalent Influenza VaccineBIOLOGICAL

For this 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
Standard-Dose Quadrivalent Influenza VaccineBIOLOGICAL

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

Also known as: QIV-SD
Standard-Dose Quadrivalent Influenza Vaccine

Eligibility Criteria

Age65 Years+
Sexall
Healthy VolunteersYes
Age GroupsOlder Adult (65+)

You may qualify if:

  • Informed consent form has been signed and dated

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

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

Hellerup, Capital Region, 2900, Denmark

Location

Danske Lægers Vaccinations Service

Søborg, 2860, Denmark

Location

Related Publications (6)

  • 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 Jan 12. doi: 10.1001/jamainternmed.2025.7286. Online ahead of print.

    PMID: 41525066DERIVED

  • 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.

    PMID: 40888720DERIVED

  • 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.

    PMID: 40884442DERIVED

  • 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.

    PMID: 40884411DERIVED

  • 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.

    PMID: 40844659DERIVED

  • 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.

    PMID: 40749884DERIVED

MeSH Terms

Conditions

Influenza, HumanPneumonia

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract DiseasesLung Diseases

Intervention Hierarchy (Ancestors)

Viral VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Tor Biering-Sørensen, MD, PhD, MPH

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

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor, MD, PhD, MPH

Study Record Dates

First Submitted

August 20, 2022

First Posted

August 26, 2022

Study Start

September 22, 2022

Primary Completion

May 31, 2025

Study Completion

August 31, 2025

Last Updated

September 12, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP

Locations

DK(2)