Pooled Analysis of Methodologically Harmonized Pragmatic Randomized Trials of High-Dose vs. Standard-Dose Influenza Vaccine Against Severe Clinical Outcomes
NCT Number: NCT06506812
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Influenza
Interventions: BIOLOGICAL: High-Dose Influenza Vaccine|BIOLOGICAL: Standard-Dose Influenza Vaccine
Sponsor: Tor Biering-Sørensen
Collaborators: Sanofi|Hospital Clinico Universitario de Santiago
Sex: ALL
Age: OLDER_ADULT
Enrollment: 450000
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2026-02

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.

Primary Outcome Measures: Hospitalization for influenza or pneumonia, ≥14 days after vaccination up to 8 months
Secondary Outcome Measures: 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 Outcome Measures: 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