Clinical trial NCT03734237: A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
Official title: A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Influenza
Influenza-like Illness
Influenza Vaccines
Keywords: Influenza vaccine
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Food and Drug Administration (FDA)
name: Defense Health Agency Immunization Healthcare Branch
name: US Department of Defense Armed Forces Health Surveillance Center
name: Naval Health Research Center
name: United States Air Force School of Aerospace Medicine
name: Uniformed Services University of the Health Sciences
First posted: 2018-11-07
Enrollment: 15449
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Laboratory Confirmed Influenza
timeFrame: Onset > 13 days after vaccination up to 1 year
Secondary outcomes:
measure: Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.
timeFrame: Baseline to 21-35 days post vaccine
measure: Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
timeFrame: Baseline to 21-35 days post vaccine
measure: Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.
timeFrame: Baseline to 21-35 days post vaccine
measure: Number of Participants With Influenza-Like Illness
timeFrame: Onset > 13 days after vaccination up to 1 year
Other outcomes:
measure: Number of Participants With SARS-CoV-2 and Influenza Co-Infection
timeFrame: Onset > 13 days after influenza vaccination up until one year
measure: Symptom Severity of SARS CoV2
timeFrame: onset >13 days after Influenza vaccination up to 1 year
Locations:
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
city: Annapolis
country: United States
facility: United States Naval Academy
state: Maryland
city: Bethesda
country: United States
facility: USU
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Fort Bragg
country: United States
facility: Womack Army Medical Center
state: North Carolina
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: San Antonio
country: United States
facility: Lackland Airforce Base
state: Texas
city: Portsmouth
country: United States
facility: Naval Medical Center Portsmouth
state: Virginia
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
Study officials:
affiliation: Uniformed Services University of the Health Sciences
name: Timothy Burgess, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Infectious Diseases Clinical Research Program
name: Rhonda Colombo, MD
role: STUDY_DIRECTOR
References:
citation: Sanchez JL, Cooper MJ, Myers CA, Cummings JF, Vest KG, Russell KL, Sanchez JL, Hiser MJ, Gaydos CA. Respiratory Infections in the U.S. Military: Recent Experience and Control. Clin Microbiol Rev. 2015 Jul;28(3):743-800. doi: 10.1128/CMR.00039-14.
citation: Flannery B, Chung JR, Belongia EA, McLean HQ, Gaglani M, Murthy K, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Foust A, Sessions W, Berman L, Barnes JR, Spencer S, Fry AM. Interim Estimates of 2017-18 Seasonal Influenza Vaccine Effectiveness - United States, February 2018. MMWR Morb Mortal Wkly Rep. 2018 Feb 16;67(6):180-185. doi: 10.15585/mmwr.mm6706a2.
citation: Zost SJ, Parkhouse K, Gumina ME, Kim K, Diaz Perez S, Wilson PC, Treanor JJ, Sant AJ, Cobey S, Hensley SE. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):12578-12583. doi: 10.1073/pnas.1712377114. Epub 2017 Nov 6.
citation: Wu NC, Zost SJ, Thompson AJ, Oyen D, Nycholat CM, McBride R, Paulson JC, Hensley SE, Wilson IA. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 2017 Oct 23;13(10):e1006682. doi: 10.1371/journal.ppat.1006682. eCollection 2017 Oct.
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citation: Wang W, Butler EN, Veguilla V, Vassell R, Thomas JT, Moos M Jr, Ye Z, Hancock K, Weiss CD. Establishment of retroviral pseudotypes with influenza hemagglutinins from H1, H3, and H5 subtypes for sensitive and specific detection of neutralizing antibodies. J Virol Methods. 2008 Nov;153(2):111-9. doi: 10.1016/j.jviromet.2008.07.015. Epub 2008 Sep 4.
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