A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Influenza Clinical Trial

— PAIVED  

Official title:

A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03734237
• Other study ID #: IDCRP-120
• Secondary ID: AAI1201200007000
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 6, 2018
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15449
• Est. completion date: May 31, 2024
• Est. primary completion date: July 7, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Influenza
• Influenza Vaccines
• Influenza, Human
• Influenza-like Illness

Intervention

Biological:
• Egg based influenza vaccines
Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.
• Recombinant influenza vaccines
Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.
• Cell-culture based influenza vaccines
Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.

Locations

Country	Name	City	State
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	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Naval Medical Center Portsmouth	Portsmouth	Virginia
United States	Lackland Airforce Base	San Antonio	Texas
United States	Naval Medical Center San Diego	San Diego	California
United States	Madigan Army Medical Center	Tacoma	Washington

Sponsors (8)

Lead Sponsor	Collaborator
Henry M. Jackson Foundation for the Advancement of Military Medicine	Armed Forces Health Surveillance Branch, Defense Health Agency Immunization Healthcare Branch, Food and Drug Administration (FDA), National Institute of Allergy and Infectious Diseases (NIAID), Naval Health Research Center, Uniformed Services University of the Health Sciences, United States Air Force School of Aerospace Medicine

Country where clinical trial is conducted

United States, 

References & Publications (8)

Cobey S, Gouma S, Parkhouse K, Chambers BS, Ertl HC, Schmader KE, Halpin RA, Lin X, Stockwell TB, Das SR, Landon E, Tesic V, Youngster I, Pinsky BA, Wentworth DE, Hensley SE, Grad YH. Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013. Clin Infect Dis. 2018 Jul 18;67(3):327-333. doi: 10.1093/cid/ciy097. — View 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. — View 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. — View Citation

Skowronski DM, Janjua NZ, De Serres G, Sabaiduc S, Eshaghi A, Dickinson JA, Fonseca K, Winter AL, Gubbay JB, Krajden M, Petric M, Charest H, Bastien N, Kwindt TL, Mahmud SM, Van Caeseele P, Li Y. Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses. PLoS One. 2014 Mar 25;9(3):e92153. doi: 10.1371/journal.pone.0092153. eCollection 2014. — View 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. — View Citation

Wang W, Xie H, Ye Z, Vassell R, Weiss CD. Characterization of lentiviral pseudotypes with influenza H5N1 hemagglutinin and their performance in neutralization assays. J Virol Methods. 2010 May;165(2):305-10. doi: 10.1016/j.jviromet.2010.02.009. Epub 2010 Feb 11. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With SARS-CoV-2 and Influenza Co-Infection	Laboratory-confirmed SARS CoV2, and SARS CoV2 plus influenza co-infection, as ascertained by nasal swab PCR.	Onset > 13 days after influenza vaccination up until one year
Other	Symptom Severity of SARS CoV2	Symptom severity scores were reported by participants using FLU-PRO Plus (Influenza Patient Reported Outcomes), a standardized instrument developed to measure the intensity and frequency of viral respiratory tract symptoms. FluPRO Plus symptom scores range from 0 ("not at all") to 4 ("very much"), with higher scores indicating greater severity.	onset >13 days after Influenza vaccination up to 1 year
Primary	Number of Participants With Laboratory Confirmed Influenza	Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.	Onset > 13 days after vaccination up to 1 year
Secondary	Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.	Strain-specific seroconversion rate determined by reference hemagglutination inhibition assay.	Baseline to 21-35 days post vaccine
Secondary	Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.	Neutralizing antibody responses (4-fold rise) to HA-psuedoviruses corresponding to vaccine-matched viruses, recently circulating influenza virus, and emerging influenza strain.	Baseline to 21-35 days post vaccine
Secondary	Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.	Anti-Neuraminidase (Anti-NA) titer responses determined by enzyme linked immuno-assay.	Baseline to 21-35 days post vaccine
Secondary	Number of Participants With Influenza-Like Illness	Rate of protocol defined influenza-like illness ascertained by participant response to active surveillance.	Onset > 13 days after vaccination up to 1 year

External Links

•   Influenza. Centers for Disease Control and Prevention