Fluad vs. Fluzone High-Dose Vaccine Effectiveness Among Adults ≥65 Years

Relative Vaccine Effectiveness of Adjuvanted Quadrivalent Inactivated Influenza Vaccine vs High-Dose Quadrivalent Inactivated Influenza Vaccine Among Adults ≥65 Years for the 2023-24 and 2024-25 Seasons

This study will evaluate the relative vaccine effectiveness of quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) versus quadrivalent high-dose inactivated influenza vaccine (HD-IIV4) in preventing polymerase chain reaction (PCR)-confirmed influenza and influenza-related outcomes in adults ≥65 years of age during the 2023/24 and 2024/25 influenza seasons. The study is an observational study conducted at Kaiser Permanente Northern California (KPNC), an integrated health care system in the United States.

Study Overview

• Status: Recruiting
• Conditions: Influenza; Community-acquired Pneumonia; Cardiovascular Events
• Intervention / Treatment: Biological: Adjuvanted Quadrivalent Inactivated Influenza Vaccine (aIIV4); Biological: High-Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV4)

• Study Type: Observational
• Enrollment (Estimated): 960000

Contacts and Locations

• Study Contact: Name: Amber H. Hyman, PhD, MPH; Phone Number: 510-267-7571; Email: Amber.Hyman@kp.org

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Recruiting
      • Kaiser Permanente Northern California (entire region)
      • Contact: Amber H. Hyman, PhD, MPH; Phone Number: 510-267-7517; Email: Amber.Hyman@kp.org
      • Principal Investigator: Nicola P. Klein, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study includes KPNC adults ≥65 years who receive Fluad or Fluzone High-Dose influenza vaccine as part of routine clinical care during the 2023/24 and/or 2024/25 influenza seasons.

Description

Inclusion Criteria:

• Age ≥65 years at the time of influenza vaccination
• KPNC member at the time of vaccination
• Receive either aIIV4 or HD-IIV4 at a KPNC facility during the 2023/24 and/or 2024/25 influenza seasons

Exclusion Criteria:

• Age <65 years at the time of influenza vaccination
• Received either aIIV4 or HD-IIV4 in the inpatient setting
• Receive more than one influenza vaccination during a single season period (i.e., 2023/24 or 2024/25 influenza seasons)
• Receive an influenza vaccination outside of KPNC

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fluad Recipients; Kaiser Permanente Northern California members aged ≥65 years who receive Adjuvanted Quadrivalent Inactivated Influenza Vaccine (aIIV4)	Biological: Adjuvanted Quadrivalent Inactivated Influenza Vaccine (aIIV4); Fluad Quadrivalent vaccine is an inactivated influenza vaccine formulated to contain 60 mcg of hemagglutinin (HA) total, with 15 mcg from each of the four recommended influenza strains and the MF59 adjuvant in single-dose prefilled 0.5 mL syringes. Kaiser Permanente Northern California members ≥65 years may receive Fluad as part of routine clinical care during the influenza season.; Other Names: Fluad
Fluzone High-Dose Recipients; Kaiser Permanente Northern California members aged ≥65 years who receive High-Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV4)	Biological: High-Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV4); Fluzone High-Dose Quadrivalent vaccine is an inactivated split virion influenza vaccine formulated to contain 240 mcg of HA total, with 60 mcg from each of the four recommended influenza strains in single-dose prefilled 0.7 mL syringes. Kaiser Permanente Northern California members ≥65 years may receive Fluzone High-Dose as part of routine clinical care during the influenza season.; Other Names: Fluzone High-Dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR-confirmed influenza	KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for the presence of PCR-confirmed influenza. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined).	≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emergency department visit or hospitalization for PCR-confirmed influenza	KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for an emergency department visit or hospitalization for PCR-confirmed influenza. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined).	≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025)
Hospitalization for PCR-confirmed influenza	KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for hospitalization for PCR-confirmed influenza. This outcome will be assessed in a pooled 2-seasons analysis (2023/24 and 2024/25 combined).	≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025)
Hospitalization for all-cause community-acquired pneumonia	KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for hospitalization for all-cause community-acquired pneumonia. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined).	≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization for cardiovascular events	KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for hospitalization for cardiovascular events. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined).	≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025)
PCR-confirmed influenza in subgroups with comorbidities	KPNC members ≥65 years with comorbidities (e.g., cardiovascular and respiratory conditions, diabetes, obesity) who receive Fluad or Fluzone High-Dose will be retrospectively assessed for hospitalization for PCR-confirmed influenza. This outcome will be assessed in a pooled 2-seasons analysis (2023/24 and 2024/25 combined).	≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025)

Collaborators and Investigators

• Sponsor: Kaiser Permanente
• Collaborators: Seqirus

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: August 28, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 2033496

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No