A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Phase 4

Active, not recruiting

• Conditions: Influenza-like Illness; Influenza; Influenza Vaccines
• Interventions: Biological: Cell-culture based influenza vaccines; Biological: Recombinant influenza vaccines; Biological: Egg based influenza vaccines

• Registration Number: NCT03734237
• Lead Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Brief Summary

A total of 18,000 eligible subjects (or 6,000 subject distributed evenly between the 3 study arms) will be enrolled. Eligible subjects will be randomized in 1:1:1 (cell-culture-based vaccine, the recombinant vaccine, or the egg-based vaccine) over four influenza seasons (2018-2019, 2019-2020, 2020-2021, and 2021-2022).

Detailed Description

This four-year, pragmatic, prospective study will compare the effectiveness of licensed egg-based inactivated influenza vaccines to the effectiveness of two other types of licensed vaccines, the cell-culture based inactivated influenza vaccine and the recombinant influenza vaccine, in the prevention of laboratory-confirmed influenza infection in active duty members, military retirees, and other DoD beneficiaries. Military treatment facilities (MTFs) in the United States will participate in this protocol. Enrollment will be restricted to adults (≥18 years and older) who are preparing to receive seasonal influenza vaccination at participating DoD sites. Subjects will be randomized to receive one of the three licensed influenza vaccines types for evaluation of effectiveness. There is no exclusion for pregnancy, as none of these licensed products are contraindicated in pregnant women.

Study Timeline

• Study First Submitted: 2018-11-02
• Study Start: 2018-11-06
• Study First Submitted QC: 2018-11-06
• Study First Posted: 2018-11-07
• Primary Completion: 2022-07-07
• Results First Submitted: 2023-08-01
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-21
• Last Update Submitted: 2023-11-21
• Results First Posted: 2023-11-24
• Last Update Posted: 2023-11-24
• Study Completion: 2024-05-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 15449

Inclusion Criteria

1. Eligible for care in Department of Defense medical facilities (Defense Enrollment Eligibility Reporting System eligible)
2. ≥18 years of age.
3. At a participating Military Treatment Facility site for the purpose of receiving a seasonal (2018-2019, 2019-2020,2020-2021, 2021-2022) influenza vaccination.
4. Able to speak English and able to provide informed consent
5. Able to receive and respond to texts and/or emails, or a military recruit

Exclusion Criteria

1. Adults intending to receive or who have received the current seasons FluMist Vaccine (LAIV)
2. Adults who have already received a flu vaccine within the current season
3. Individual who cannot receive a flu vaccine or standard dosing due to another medical condition
4. Allergic to gentamicin, polymyxin and/or neomycin
5. Individuals who fail to meet the inclusion criteria

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cell-culture based influenza vaccines	Cell-culture based influenza vaccines	Flucelvax, Madin-Darby canine kidney (MDCK)-cell-culture based inactivated influenza vaccine. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. Flucelvax quadrivalent, the only cell-based flu vaccine FDA licensed for use in the United States.
Recombinant influenza vaccines	Recombinant influenza vaccines	FluBlok, recombinant HA influenza vaccine. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. Flublok Quadrivalent is a quadrivalent recombinant influenza vaccine that has been licensed by the FDA for use in the United States.
Egg based influenza vaccines	Egg based influenza vaccines	Quadrivalent egg-based vaccines, which contain an inactivated form of the virus. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. All egg-based vaccines are FDA licensed for use in the United States.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Laboratory Confirmed Influenza	Onset > 13 days after vaccination up to 1 year	Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.

Secondary Outcome Measures

Name	Time	Method
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.	Baseline to 21-35 days post vaccine	Neutralizing antibody responses (4-fold rise) to HA-psuedoviruses corresponding to vaccine-matched viruses, recently circulating influenza virus, and emerging influenza strain.
Number of Participants With Influenza-Like Illness	Onset > 13 days after vaccination up to 1 year	Rate of protocol defined influenza-like illness ascertained by participant response to active surveillance.
Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.	Baseline to 21-35 days post vaccine	Strain-specific seroconversion rate determined by reference hemagglutination inhibition assay.
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.	Baseline to 21-35 days post vaccine	Anti-Neuraminidase (Anti-NA) titer responses determined by enzyme linked immuno-assay.

Trial Locations

Locations (9)

Naval Medical Center San Diego; 🇺🇸 San Diego, California, United States

United States Naval Academy; 🇺🇸 Annapolis, Maryland, United States

USU; 🇺🇸 Bethesda, Maryland, United States

Walter Reed National Military Medical Center; 🇺🇸 Bethesda, Maryland, United States

Womack Army Medical Center; 🇺🇸 Fort Bragg, North Carolina, United States

Naval Medical Center Portsmouth; 🇺🇸 Portsmouth, Virginia, United States

Brooke Army Medical Center; 🇺🇸 Fort Sam Houston, Texas, United States

Madigan Army Medical Center; 🇺🇸 Tacoma, Washington, United States

Lackland Airforce Base; 🇺🇸 San Antonio, Texas, United States