Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting

Study Overview
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Brief Summary
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The purpose of the study is to assess the feasibility of identifying, recruiting and randomizing a large sample of Danish citizens aged 65-79 years to high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine in the 2021/2022 influenza season in a registry-based setting using Danish nationwide registries for all data collection including baseline information and outcome assessment.

Detailed Description
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To evaluate the feasibility of recruiting and randomizing Danish citizens aged 65-79 years, we aim to randomize 40,000 citizens 1:1 to high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine in a pragmatic, open-label, registry-based design using the infrastructure of Danske Lægers Vaccinations Service (DLVS), an organization responsible for numerous vaccination clinics in Denmark, for recruitment and randomization and Danish nationwide registries for data collection. Citizens will be recruited by DLVS and randomized and vaccinated at the DLVS clinics. All collection of data related to baseline information, outcomes, and safety monitoring will be performed by a central trial site utilizing information from Danish nationwide health registries. The findings of this pilot trial will indicate whether the conduction of a full-scale, adequately powered pragmatic RCT is feasible within the Danish registry-based framework.

Official Title
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Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine vs. Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting

Conditions
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Influenza

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65-79 years Informed consent form has been signed and dated Exclusion Criteria: 1. Allergy/hypersensitivity towards the influenza vaccines used in this study

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 79 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 |
| --- | --- |
| Active Comparator: Standard-Dose Quadrivalent Influenza Vaccine<br>QIV-SD single injection at Day 0 | Drug: Standard-Dose Quadrivalent Influenza Vaccine<br>* For the control arm, the standard-dose quadrivalent influenza vaccines Influvactetra® and Vaxigriptetra will be used.<br>* Other names: QIV-SD;|
| Experimental: High-Dose Quadrivalent Influenza Vaccine<br>QIV-HD single injection at Day 0 | Drug: High-Dose Quadrivalent Influenza Vaccine<br>* For the control arm, the high-dose quadrivalent influenza vaccine Efluelda®/Fluzone® High-Dose Quadrivalent will be used.<br>* Other names: QIV-HD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of persons contacted by recruitment letter |  | Up to 8 months | 
| Number of participants included and randomized to QIV-HD or QIV-SD |  | Up to 8 months | 
| Agreement between randomization assignment and actual received vaccine |  | Up to 8 months | 
| Balance between groups in terms of number of subjects in each arm and baseline characteristics |  | Up to 8 months | 
| Comparison of baseline characteristics for the QIV-HD and QIV-SD groups to the overall Danish general population aged 65-79 years |  | Up to 8 months | 
| Comparison of baseline characteristics for the QIV-HD and QIV-SD groups to the population aged 65-79 years in the DLVS database used for recruitment |  | Up to 8 months | 
| Description of event rates and calculation of relative vaccine effectiveness for hospitalization for influenza and/or pneumonia | First hospitalization with a primary (A) diagnosis code for influenza or pneumonia of at least 1 night duration | >= 14 days after vaccination up to 8 months post-vaccination | 
| Description of event rates and calculation of relative vaccine effectiveness for hospitalization for respiratory disease | First hospitalization with a primary (A) diagnosis code for respiratory disease of at least 1 night duration | >= 14 days after vaccination up to 8 months post-vaccination | 
| Description of event rates and calculation of relative vaccine effectiveness for hospitalization for cardio-respiratory disease | First hospitalization with a primary (A) diagnosis code for cardio-respiratory disease of at least 1 night duration | >= 14 days after vaccination up to 8 months post-vaccination | 
| Description of event rates and calculation of relative vaccine effectiveness for hospitalization for cardiovascular disease | First hospitalization with a primary (A) diagnosis code for cardiovascular disease of at least 1 night duration | >= 14 days after vaccination up to 8 months post-vaccination | 
| Description of event rates and calculation of relative vaccine effectiveness for hospitalization from any cause | First hospitalization with any diagnosis code of at least 1 night duration | >= 14 days after vaccination up to 8 months post-vaccination | 
| Description of event rates and calculation of relative vaccine effectiveness for all-cause mortality | Death from any cause | >= 14 days after vaccination up to 8 months post-vaccination | 
| Description of event rates and calculation of relative vaccine effectiveness for hospitalization for COVID-19 | First hospitalization with a primary (A) diagnosis code for COVID-19 of at least 1 night duration | >= 14 days after vaccination up to 8 months post-vaccination | 

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