Clinical trial NCT05517174: A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults
Official title: A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Influenza
Keywords: Influenza
Vaccination
Pragmatic
Registry
Pneumonia
Respiratory
Cardiovascular
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Statens Serum Institut
First posted: 2022-08-26
Enrollment: 339700
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hospitalization for influenza or pneumonia
timeFrame: ≥14 days after vaccination up to 8 months
Secondary outcomes:
measure: Hospitalization for any cardio-respiratory disease
timeFrame: ≥14 days after vaccination up to 8 months
measure: All-cause hospitalization
timeFrame: ≥14 days after vaccination up to 8 months
measure: All-cause mortality
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for influenza
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for pneumonia
timeFrame: ≥14 days after vaccination up to 8 months
Other outcomes:
measure: Hospitalization for influenza or pneumonia (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for pneumonia (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for influenza (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for any respiratory disease
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for any cardiovascular disease
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for myocardial infarction
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for heart failure
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for atrial fibrillation
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for stroke
timeFrame: ≥14 days after vaccination up to 8 months
measure: Major adverse cardiovascular events (MACE) defined as a composite of hospitalization for acute myocardial infarction, hospitalization for stroke, and cardiovascular death
timeFrame: ≥14 days after vaccination up to 8 months
measure: MACE defined as a composite of hospitalization for acute myocardial infarction, hospitalization for stroke, hospitalization for heart failure, and cardiovascular death (alternate definition #1)
timeFrame: ≥14 days after vaccination up to 8 months
measure: MACE defined as a composite of hospitalization for acute myocardial infarction, hospitalization for stroke, and all-cause death (alternate definition #2)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization requiring mechanical ventilation
timeFrame: ≥14 days after vaccination up to 8 months
measure: Laboratory-confirmed influenza
timeFrame: ≥14 days after vaccination up to 8 months
measure: Laboratory-confirmed pneumococcal pneumonia
timeFrame: ≥14 days after vaccination up to 8 months
measure: Laboratory-confirmed COVID-19
timeFrame: ≥14 days after vaccination up to 8 months
measure: Cardio-respiratory mortality
timeFrame: ≥14 days after vaccination up to 8 months
measure: Respiratory mortality
timeFrame: ≥14 days after vaccination up to 8 months
measure: Cardiovascular mortality
timeFrame: ≥14 days after vaccination up to 8 months
measure: In-hospital mortality
timeFrame: ≥14 days after vaccination up to 8 months
measure: Intensive care unit admission
timeFrame: ≥14 days after vaccination up to 8 months
measure: Laboratory-confirmed influenza hospitalization
timeFrame: ≥14 days after vaccination up to 8 months
measure: Any hospital contact associated with laboratory-confirmed influenza
timeFrame: ≥14 days after vaccination up to 8 months
measure: Any exacerbation of pre-existing chronic obstructive pulmonary disease
timeFrame: ≥14 days after vaccination up to 8 months
measure: Any exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Severe exacerbation of pre-existing chronic obstructive pulmonary disease
timeFrame: ≥14 days after vaccination up to 8 months
measure: Severe exacerbation of pre-existing chronic obstructive pulmonary disease (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Any exacerbation of pre-existing asthma
timeFrame: ≥14 days after vaccination up to 8 months
measure: Any exacerbation of pre-existing asthma (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Severe exacerbation of pre-existing asthma
timeFrame: ≥14 days after vaccination up to 8 months
measure: Severe exacerbation of pre-existing asthma (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Exacerbation of pre-existing heart failure
timeFrame: ≥14 days after vaccination up to 8 months
measure: Exacerbation of pre-existing heart failure (alternate definition)
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for pericarditis
timeFrame: ≥14 days after vaccination up to 8 months
measure: Hospitalization for myocarditis
timeFrame: ≥14 days after vaccination up to 8 months
measure: New-onset dementia
timeFrame: ≥14 days after vaccination up to 8 months
Locations:
city: Hellerup
country: Denmark
facility: Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
state: Hovedstaden
city: Søborg
country: Denmark
facility: Danske Lægers Vaccinations Service
Study officials:
affiliation: Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
name: Tor Biering-Sørensen, MD, PhD, MPH
role: STUDY_CHAIR
References: