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

Study Overview
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Brief Summary
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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
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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 286,900 participants over 3 influenza seasons. In each season, participants will be individually randomized 1:1 to receive either QIV-HD or QIV-SD.

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

Conditions
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Influenza

Intervention / Treatment
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* Biological: High-Dose Quadrivalent Influenza Vaccine
* Biological: Standard-Dose Quadrivalent Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Dose Quadrivalent Influenza Vaccine<br>QIV-HD single injection at Day 0 | Biological: High-Dose Quadrivalent Influenza Vaccine<br>* For this arm, the high-dose quadrivalent influenza vaccine Efluelda®/Fluzone® High-Dose Quadrivalent will be used as the active comparator.<br>* Other names: QIV-HD;|
| Active Comparator: Standard-Dose Quadrivalent Influenza Vaccine<br>QIV-SD single injection at Day 0 | Biological: Standard-Dose Quadrivalent Influenza Vaccine<br>* Any standard-dose quadrivalent influenza vaccine administered in the Danish governmental influenza vaccine program may be used.<br>* Other names: QIV-SD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization for influenza or pneumonia |  | ≥14 days after vaccination up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Vaccination, Pragmatic, Registry, Pneumonia, Respiratory, Cardiovascular