A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults

Phase 4

Active, not recruiting

• Conditions: Influenza
• Interventions: Biological: High-Dose Quadrivalent Influenza Vaccine; Biological: Standard-Dose Quadrivalent Influenza Vaccine

• Registration Number: NCT05517174
• Lead Sponsor: Tor Biering-Sørensen

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.

Study Timeline

• Study First Submitted: 2022-08-20
• Study First Submitted QC: 2022-08-24
• Study First Posted: 2022-08-26
• Study Start: 2022-09-22
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Primary Completion: 2025-05-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 286900

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High-Dose Quadrivalent Influenza Vaccine	High-Dose Quadrivalent Influenza Vaccine	QIV-HD single injection at Day 0
Standard-Dose Quadrivalent Influenza Vaccine	Standard-Dose Quadrivalent Influenza Vaccine	QIV-SD single injection at Day 0

Primary Outcome Measures

Name	Time	Method
Hospitalization for influenza or pneumonia	≥14 days after vaccination up to 8 months

Secondary Outcome Measures

Name	Time	Method
Hospitalization for pneumonia	≥14 days after vaccination up to 8 months
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

Trial Locations

Locations (2)

Danske Lægers Vaccinations Service; 🇩🇰 Søborg, Denmark

Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte; 🇩🇰 Hellerup, Hovedstaden, Denmark