Clinical trial NCT06506812: Pooled Analysis of Methodologically Harmonized Pragmatic Randomized Trials of High-Dose vs. Standard-Dose Influenza Vaccine Against Severe Clinical Outcomes
Official title: Pooled Analysis of Methodologically Harmonized Pragmatic Randomized Trials of High-Dose vs. Standard-Dose Influenza Vaccine Against Severe Clinical Outcomes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Influenza
Keywords: Influenza
Vaccination
Pragmatic
Registry
Pneumonia
Respiratory
Cardiovascular
Meta-analysis
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Hospital Clinico Universitario de Santiago
First posted: 2024-07-18
Enrollment: 450000
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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: Laboratory-confirmed influenza hospitalization
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: 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:
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, MSc, MPH, PhD
role: STUDY_CHAIR
References: