Pooled Analysis of Methodologically Harmonized Pragmatic Randomized Trials of High-Dose vs. Standard-Dose Influenza Vaccine Against Severe Clinical Outcomes (FLUNITY-HD)

September 8, 2025 updated by: Tor Biering-Sørensen
This prespecified analysis will pool the datasets from two pragmatic randomized trials evaluating the relative vaccine effectiveness of high-dose vs. standard-dose influenza vaccine against severe clinical outcomes: the DANFLU-2 (A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults) trial and the GALFLU (Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in Adults Aged 65 to 79 Years in Galicia, Spain) trial. The purpose of the pooled analysis is to ensure adequate statistical power for evaluating relative vaccine effectiveness against severe clinical outcomes and to increase generalizability of the results by combining data from two countries.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
466320

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
    • Capital Region
      • Hellerup, Capital Region, Denmark, 2900
        • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pragmatic trials conducted to estimate the relative vaccine effectiveness of high-dose influenza vaccine compared with standard-dose influenza vaccine using the DANFLU-2 protocol or a protocol developed based on the DANFLU-2 protocol

Exclusion Criteria:

  • Low data quality
  • Influenza circulation threshold was not met in any of the study seasons
  • Severe under-enrollment in all seasons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: High-Dose Influenza Vaccine
Single injection of high-dose influenza vaccine at Day 0
Biological: High-Dose Influenza Vaccine
For this arm, the high-dose quadrivalent influenza vaccine Efluelda®/Fluzone® High-Dose Quadrivalent will be used.
Active Comparator: Standard-Dose Influenza Vaccine
Single injection of standard-dose influenza vaccine at Day 0
Biological: Standard-Dose Influenza Vaccine
Any standard-dose quadrivalent influenza vaccine administered in the governmental influenza vaccine programs may be used.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Hospitalization for influenza or pneumonia
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Hospitalization for any cardio-respiratory disease
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
All-cause hospitalization
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
All-cause mortality
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for influenza
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for pneumonia
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Laboratory-confirmed influenza hospitalization
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Hospitalization for influenza or pneumonia (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for pneumonia (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for influenza (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for any respiratory disease
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for any cardiovascular disease
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for myocardial infarction
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for heart failure
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for atrial fibrillation
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for stroke
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
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
≥14 days after vaccination up to 8 months
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
≥14 days after vaccination up to 8 months
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
≥14 days after vaccination up to 8 months
Hospitalization requiring mechanical ventilation
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Laboratory-confirmed influenza
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Laboratory-confirmed pneumococcal pneumonia
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Laboratory-confirmed COVID-19
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Cardio-respiratory mortality
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Respiratory mortality
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Cardiovascular mortality
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
In-hospital mortality
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Intensive care unit admission
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Any hospital contact associated with laboratory-confirmed influenza
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Any exacerbation of pre-existing chronic obstructive pulmonary disease
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Any exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Severe exacerbation of pre-existing chronic obstructive pulmonary disease
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Severe exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Any exacerbation of pre-existing asthma
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Any exacerbation of pre-existing asthma (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Severe exacerbation of pre-existing asthma
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Severe exacerbation of pre-existing asthma (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Exacerbation of pre-existing heart failure
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Exacerbation of pre-existing heart failure (alternate definition)
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for pericarditis
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
Hospitalization for myocarditis
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months
New-onset dementia
Time Frame: ≥14 days after vaccination up to 8 months
≥14 days after vaccination up to 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tor Biering-Sørensen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sanofi
Hospital Clinico Universitario de Santiago

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Tor Biering-Sørensen, MD, MSc, MPH, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 31, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 12, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 12, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 8, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DANFLU/GALFLU pooled analysis

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In each trial, baseline and endpoint data will be collected from administrative health registries, which are subject to local legislation and can only be made available to a third party under certain conditions. Please contact the sponsor in case of any inquiries.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings