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

NCT06506812 | Completed Phase 4

• 1 other identifier: DANFLU/GALFLU pooled analysis
• Study Type: interventional
• Target: 466,320
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Influenza

Keywords

Influenza; Vaccination; Pragmatic; Registry; Pneumonia; Respiratory; Cardiovascular; Meta-analysis

Outcome Measures

Primary Outcomes (1)

• Hospitalization for influenza or pneumonia

  ≥14 days after vaccination up to 8 months

Secondary Outcomes (6)

• Hospitalization for any cardio-respiratory disease

  ≥14 days after vaccination up to 8 months

• Laboratory-confirmed influenza hospitalization

  ≥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

Other Outcomes (35)

• 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

Study Arms (2)

High-Dose Influenza Vaccine

EXPERIMENTAL

Single injection of high-dose influenza vaccine at Day 0

Biological: High-Dose Influenza Vaccine

Standard-Dose Influenza Vaccine

ACTIVE COMPARATOR

Single injection of standard-dose influenza vaccine at Day 0

Biological: Standard-Dose Influenza Vaccine

Interventions

High-Dose Influenza Vaccine BIOLOGICAL

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

High-Dose Influenza Vaccine

Standard-Dose Influenza Vaccine BIOLOGICAL

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

Standard-Dose Influenza Vaccine

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Tor Biering-Sørensen: lead
• Sanofi: collaborator
• Hospital Clinico Universitario de Santiago: collaborator

Study Sites (1)

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

Hellerup, Capital Region, 2900, Denmark

Location

Related Publications (1)

• Johansen ND, Modin D, Pardo-Seco J, Rodriguez-Tenreiro-Sanchez C, Loiacono MM, Harris RC, Dufournet M, van Aalst R, Chit A, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Claggett BL, Janstrup KH, Duran-Parrondo C, Pineiro-Sotelo M, Cribeiro-Gonzalez M, Conde-Pajaro M, Miras-Carballal S, Gonzalez-Perez JM, Solomon SD, Sivapalan P, Martel CJ, Jensen JUS, Martinon-Torres F, Biering-Sorensen T; DANFLU-2 Study Group; GALFLU Trial Team. Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis. Lancet. 2025 Nov 22;406(10518):2425-2434. doi: 10.1016/S0140-6736(25)01742-8. Epub 2025 Oct 17.

  PMID: 41115437 DERIVED

MeSH Terms

Conditions

Influenza, Human; Pneumonia

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• 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 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, MSc, MPH, PhD

Study Record Dates

• First Submitted: July 12, 2024
• First Posted: July 18, 2024
• Study Start: May 31, 2025
• 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
• Shared Documents: STUDY PROTOCOL, SAP

Locations

DK (1)