Influenza
Conditions
Keywords
Influenza, Vaccination, Pragmatic, Registry, Pneumonia, Respiratory, Cardiovascular
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.
Detailed description
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.
Interventions
BIOLOGICALHigh-Dose Quadrivalent Influenza Vaccine
For this arm, the high-dose quadrivalent influenza vaccine Efluelda®/Fluzone® High-Dose Quadrivalent will be used.
Any standard-dose quadrivalent influenza vaccine administered in the Danish governmental influenza vaccine program may be used.
Sponsors
Sanofi
Statens Serum Institut
Tor Biering-Sørensen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hospitalization for influenza or pneumonia | ≥14 days after vaccination up to 8 months |
Secondary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Laboratory-confirmed influenza hospitalization | ≥14 days after vaccination up to 8 months |
| Hospitalization for myocarditis | ≥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 |
| Exacerbation of pre-existing heart failure | ≥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 |
| Any hospital contact associated with laboratory-confirmed influenza | ≥14 days after vaccination up to 8 months |
| New-onset dementia | ≥14 days after vaccination up to 8 months |
| Hospitalization for influenza or pneumonia (alternate definition) | ≥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 pneumonia (alternate definition) | ≥14 days after vaccination up to 8 months |
Countries
Denmark
Outcome results
None listed