| Registry | NCT06506812, acronym FLUNITY-HD |
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| Status | Completed |
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| Phase | Phase 4 |
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| Study type | Interventional; randomized, parallel, masking: none, treatment |
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| Enrollment | 466320 (Actual) |
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| Sponsor | Tor Biering-Sørensen (Other); collaborators: Sanofi, Hospital Clinico Universitario de Santiago |
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| Conditions | Influenza |
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| Interventions | High-Dose Influenza Vaccine, Standard-Dose Influenza Vaccine (Biological) |
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| Dates | start 2025-05-31, primary completion 2025-05-31, completion 2025-08-31, first posted 2024-07-18, last updated 2025-09-12 |
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| Locations | 1 site in Denmark |
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Related Papers Related Patents Related Grants Related Experts
All trials for Influenza All trials of High-Dose Influenza Vaccine All trials of Standard-Dose Influenza Vaccine
-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.
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+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| High-Dose Influenza Vaccine | Experimental | Biological: High-Dose Influenza Vaccine | Single injection of high-dose influenza vaccine at Day 0 |
| Standard-Dose Influenza Vaccine | Active comparator | Biological: Standard-Dose Influenza Vaccine | Single injection of standard-dose influenza vaccine at Day 0 |
- High-Dose Influenza Vaccine (Biological): For this arm, the high-dose quadrivalent influenza vaccine Efluelda®/Fluzone® High-Dose Quadrivalent will be used.
- Standard-Dose Influenza Vaccine (Biological): Any standard-dose quadrivalent influenza vaccine administered in the governmental influenza vaccine programs may be used.
+Outcome measures
Primary outcomes
- Hospitalization for influenza or pneumonia [≥14 days after vaccination up to 8 months]
Secondary outcomes
- 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]
- Hospitalization for pneumonia [≥14 days after vaccination up to 8 months]
Other outcomes
- 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]
- Hospitalization for any respiratory disease [≥14 days after vaccination up to 8 months]
- Hospitalization for any cardiovascular disease [≥14 days after vaccination up to 8 months]
- Hospitalization for myocardial infarction [≥14 days after vaccination up to 8 months]
- Hospitalization for heart failure [≥14 days after vaccination up to 8 months]
- Hospitalization for atrial fibrillation [≥14 days after vaccination up to 8 months]
- Hospitalization for stroke [≥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 [≥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) [≥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) [≥14 days after vaccination up to 8 months]
- Hospitalization requiring mechanical ventilation [≥14 days after vaccination up to 8 months]
- Laboratory-confirmed influenza [≥14 days after vaccination up to 8 months]
- Laboratory-confirmed pneumococcal pneumonia [≥14 days after vaccination up to 8 months]
- Laboratory-confirmed COVID-19 [≥14 days after vaccination up to 8 months]
- Cardio-respiratory mortality [≥14 days after vaccination up to 8 months]
- Respiratory mortality [≥14 days after vaccination up to 8 months]
- Cardiovascular mortality [≥14 days after vaccination up to 8 months]
- In-hospital mortality [≥14 days after vaccination up to 8 months]
- Intensive care unit admission [≥14 days after vaccination up to 8 months]
- Any hospital contact associated with laboratory-confirmed influenza [≥14 days after vaccination up to 8 months]
- Any exacerbation of pre-existing chronic obstructive pulmonary disease [≥14 days after vaccination up to 8 months]
- Any exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition) [≥14 days after vaccination up to 8 months]
- Severe exacerbation of pre-existing chronic obstructive pulmonary disease [≥14 days after vaccination up to 8 months]
- Severe exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition) [≥14 days after vaccination up to 8 months]
- Any exacerbation of pre-existing asthma [≥14 days after vaccination up to 8 months]
- Any exacerbation of pre-existing asthma (alternate definition) [≥14 days after vaccination up to 8 months]
- Severe exacerbation of pre-existing asthma [≥14 days after vaccination up to 8 months]
- Severe exacerbation of pre-existing asthma (alternate definition) [≥14 days after vaccination up to 8 months]
- Exacerbation of pre-existing heart failure [≥14 days after vaccination up to 8 months]
- Exacerbation of pre-existing heart failure (alternate definition) [≥14 days after vaccination up to 8 months]
- Hospitalization for pericarditis [≥14 days after vaccination up to 8 months]
- Hospitalization for myocarditis [≥14 days after vaccination up to 8 months]
- New-onset dementia [≥14 days after vaccination up to 8 months]
+Eligibility
Sex: All, ages: 65 Years to any
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
+Locations (1)
| Facility | City | Country | Status |
|---|
| Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte | Hellerup, Capital Region | Denmark | |
+Publications
- Results publication: 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 and the GALFLU Trial Team. High-Dose Versus Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: The FLUNITY-HD Prespecified Pooled Analysis. Circulation. 2026 Mar 17;153(11):798-806. doi: 10.1161/CIRCULATIONAHA.125.077801. Epub 2025 Nov 10. PMID 41212981
- Results publication: 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
+Investigators
- Tor Biering-Sørensen, MD, MSc, MPH, PhD, Study chair, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte