PAIVED: A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03734237
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Food and Drug Administration (FDA) (U.S. Fed), Defense Health Agency Immunization Healthcare Branch (Other), Armed Forces Health Surveillance Branch (Other), Naval Health Research Center (U.S. Fed), United States Air Force School of Aerospace Medicine (Other), Uniformed Services University of the Health Sciences (U.S. Fed)
• Enrollment: 18,000
• Locations: 9
• Arms: 3
• Anticipated Duration (Months): 42.8
• Patients Per Site: 2000
• Patients Per Site Per Month: 46.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Influenza; Influenza-like Illness; Influenza Vaccines	Biological: Egg based influenza vaccines; Biological: Recombinant influenza vaccines; Biological: Cell-culture based influenza vaccines	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 18000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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).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).
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
• Actual Study Start Date: Nov 6, 2018
• Anticipated Primary Completion Date: May 31, 2022
• Anticipated Study Completion Date: May 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	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.
Active Comparator: 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.	Biological: 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.
Active Comparator: 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.	Biological: 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.

Outcome Measures

Primary Outcome Measures

1. Laboratory confirmed influenza attack rates [Onset > 13 days after vaccination up to 1 year]

   Laboratory-confirmed influenza as ascertained by a sensitive and specific assay is needed to assess effectiveness.

Secondary Outcome Measures

1. Hemagglutination Inhibition (HI) titer responses to vaccine and circulating strains of influenza [Baseline to 21-35 days post vaccine]

   A subset of volunteers may participate it in this outcome.

2. Pseudovirion neutralization (PVN) responses to vaccine and circulating strains of influenza [Baseline to 21-35 days post vaccine]

   A subset of volunteers may participate it in this outcome.

3. Anti-Neuraminidase (Anti-NA) titer responses to vaccine and circulating strains of influenza [Baseline to 21-35 days post vaccine]

   A subset of volunteers may participate it in this outcome.

4. Cellular Responses: Frequency of antigen specific CD4 and CD8 cells, B cells [Baseline to 21-35 days post vaccine]

   A subset of volunteers may participate it in this outcome.

5. Rate of Influenza-like Illness [Onset > 13 days after vaccination up to 1 year]

6. Frequency of influenza confirmed hospitalization [Onset > 13 days after vaccination up to 1 year]

7. Number of duty (work) days lost due to Influenza-like Illness [Onset > 13 days after vaccination up to 1 year]

Other Outcome Measures

1. Tertiary Arm- Assess the burden of covid-19 and explore the inter-relationship between influenza and covid-19 [onset >13 days after vaccination]

   Endpoints: incidence of COVID-19 incidence of co-infection with influenza & Severity of COVID-19, symptoms associated with COVID-19 infection (compared with influenza, other respiratory viruses)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Naval Medical Center San Diego	San Diego	California	United States	34800
2	United States Naval Academy	Annapolis	Maryland	United States	21402
3	USU	Bethesda	Maryland	United States	20307
4	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20814
5	Womack Army Medical Center	Fort Bragg	North Carolina	United States	28310
6	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
7	Lackland Airforce Base	San Antonio	Texas	United States	78243
8	Naval Medical Center Portsmouth	Portsmouth	Virginia	United States	23704
9	Madigan Army Medical Center	Tacoma	Washington	United States	98431

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Timothy Burgess, MD, Uniformed Services University of the Health Sciences
• Study Director: Rhonda Colombo, MD, Infectious Diseases Clinical Research Program

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Influenza. Centers for Disease Control and Prevention

Publications

• 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.
• 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.
• 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. Review.
• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Henry M. Jackson Foundation for the Advancement of Military Medicine
• ClinicalTrials.gov Identifier: NCT03734237
• Other Study ID Numbers: IDCRP-120; AAI1201200007000
• First Posted: Nov 7, 2018
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Henry M. Jackson Foundation for the Advancement of Military Medicine: Influenza vaccine
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

No Results Posted as of Jan 11, 2022