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Completed

NCT Number: NCT05517174

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

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.

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Key information

Conditions

Influenza Infections Influenza, Human Lung Diseases Orthomyxoviridae Infections Pneumonia RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • There are no specific exclusion criteria for this study

Treatment and study plan

High-Dose Quadrivalent Influenza Vaccine

Biological

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

Other names: QIV-HD

Standard-Dose Quadrivalent Influenza Vaccine

Biological

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

Other names: QIV-SD

Primary outcomes

  1. Hospitalization for influenza or pneumonia

    Time frame: ≥14 days after vaccination up to 8 months

Secondary outcomes

  1. Hospitalization for any cardio-respiratory disease

    Time frame: ≥14 days after vaccination up to 8 months

  2. All-cause hospitalization

    Time frame: ≥14 days after vaccination up to 8 months

  3. All-cause mortality

    Time frame: ≥14 days after vaccination up to 8 months

  4. Hospitalization for influenza

    Time frame: ≥14 days after vaccination up to 8 months

  5. Hospitalization for pneumonia

    Time frame: ≥14 days after vaccination up to 8 months

Other outcomes

  1. Hospitalization for influenza or pneumonia (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  2. Hospitalization for pneumonia (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  3. Hospitalization for influenza (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  4. Hospitalization for any respiratory disease

    Time frame: ≥14 days after vaccination up to 8 months

  5. Hospitalization for any cardiovascular disease

    Time frame: ≥14 days after vaccination up to 8 months

  6. Hospitalization for myocardial infarction

    Time frame: ≥14 days after vaccination up to 8 months

  7. Hospitalization for heart failure

    Time frame: ≥14 days after vaccination up to 8 months

  8. Hospitalization for atrial fibrillation

    Time frame: ≥14 days after vaccination up to 8 months

  9. Hospitalization for stroke

    Time frame: ≥14 days after vaccination up to 8 months

  10. Major adverse cardiovascular events (MACE) defined as a composite of hospitalization for acute myocardial infarction, hospitalization for stroke, and cardiovascular death

    Time frame: ≥14 days after vaccination up to 8 months

  11. MACE defined as a composite of hospitalization for acute myocardial infarction, hospitalization for stroke, hospitalization for heart failure, and cardiovascular death (alternate definition #1)

    Time frame: ≥14 days after vaccination up to 8 months

  12. MACE defined as a composite of hospitalization for acute myocardial infarction, hospitalization for stroke, and all-cause death (alternate definition #2)

    Time frame: ≥14 days after vaccination up to 8 months

  13. Hospitalization requiring mechanical ventilation

    Time frame: ≥14 days after vaccination up to 8 months

  14. Laboratory-confirmed influenza

    Time frame: ≥14 days after vaccination up to 8 months

  15. Laboratory-confirmed pneumococcal pneumonia

    Time frame: ≥14 days after vaccination up to 8 months

  16. Laboratory-confirmed COVID-19

    Time frame: ≥14 days after vaccination up to 8 months

  17. Cardio-respiratory mortality

    Time frame: ≥14 days after vaccination up to 8 months

  18. Respiratory mortality

    Time frame: ≥14 days after vaccination up to 8 months

  19. Cardiovascular mortality

    Time frame: ≥14 days after vaccination up to 8 months

  20. In-hospital mortality

    Time frame: ≥14 days after vaccination up to 8 months

  21. Intensive care unit admission

    Time frame: ≥14 days after vaccination up to 8 months

  22. Laboratory-confirmed influenza hospitalization

    Time frame: ≥14 days after vaccination up to 8 months

  23. Any hospital contact associated with laboratory-confirmed influenza

    Time frame: ≥14 days after vaccination up to 8 months

  24. Any exacerbation of pre-existing chronic obstructive pulmonary disease

    Time frame: ≥14 days after vaccination up to 8 months

  25. Any exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  26. Severe exacerbation of pre-existing chronic obstructive pulmonary disease

    Time frame: ≥14 days after vaccination up to 8 months

  27. Severe exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  28. Any exacerbation of pre-existing asthma

    Time frame: ≥14 days after vaccination up to 8 months

  29. Any exacerbation of pre-existing asthma (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  30. Severe exacerbation of pre-existing asthma

    Time frame: ≥14 days after vaccination up to 8 months

  31. Severe exacerbation of pre-existing asthma (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  32. Exacerbation of pre-existing heart failure

    Time frame: ≥14 days after vaccination up to 8 months

  33. Exacerbation of pre-existing heart failure (alternate definition)

    Time frame: ≥14 days after vaccination up to 8 months

  34. Hospitalization for pericarditis

    Time frame: ≥14 days after vaccination up to 8 months

  35. Hospitalization for myocarditis

    Time frame: ≥14 days after vaccination up to 8 months

  36. New-onset dementia

    Time frame: ≥14 days after vaccination up to 8 months

Sponsors and collaborators

Lead sponsor

Tor Biering-Sørensen

Other

Collaborators

  • Sanofi
  • Statens Serum Institut

Registry information

Acronym: DANFLU-2

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Aug 26, 2022
Registry last updated
Sep 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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