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A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED)

Primary Purpose

Influenza, Influenza-like Illness, Influenza Vaccines

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Egg based influenza vaccines
Recombinant influenza vaccines
Cell-culture based influenza vaccines
Sponsored by
Henry M. Jackson Foundation for the Advancement of Military Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring Influenza vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Naval Medical Center San Diego
  • United States Naval Academy
  • USU
  • Walter Reed National Military Medical Center
  • Womack Army Medical Center
  • Brooke Army Medical Center
  • Lackland Airforce Base
  • Naval Medical Center Portsmouth
  • Madigan Army Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Egg based influenza vaccines

Recombinant influenza vaccines

Cell-culture based influenza vaccines

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Hemagglutination Inhibition (HI) titer responses to vaccine and circulating strains of influenza
A subset of volunteers may participate it in this outcome.
Pseudovirion neutralization (PVN) responses to vaccine and circulating strains of influenza
A subset of volunteers may participate it in this outcome.
Anti-Neuraminidase (Anti-NA) titer responses to vaccine and circulating strains of influenza
A subset of volunteers may participate it in this outcome.
Cellular Responses: Frequency of antigen specific CD4 and CD8 cells, B cells
A subset of volunteers may participate it in this outcome.
Rate of Influenza-like Illness
Frequency of influenza confirmed hospitalization
Number of duty (work) days lost due to Influenza-like Illness

Full Information

First Posted
November 2, 2018
Last Updated
June 22, 2023
Sponsor
Henry M. Jackson Foundation for the Advancement of Military Medicine
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT03734237
Brief Title
A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
Acronym
PAIVED
Official Title
A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 6, 2018 (Actual)
Primary Completion Date
July 7, 2022 (Actual)
Study Completion Date
May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Henry M. Jackson Foundation for the Advancement of Military Medicine
Collaborators
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

4. Oversight

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
Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Influenza-like Illness, Influenza Vaccines
Keywords
Influenza vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16023 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Egg based influenza vaccines
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Recombinant influenza vaccines
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Cell-culture based influenza vaccines
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Egg based influenza vaccines
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Recombinant influenza vaccines
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Cell-culture based influenza vaccines
Intervention Description
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.
Primary Outcome Measure Information:
Title
Laboratory confirmed influenza attack rates
Description
Laboratory-confirmed influenza as ascertained by a sensitive and specific assay is needed to assess effectiveness.
Time Frame
Onset > 13 days after vaccination up to 1 year
Secondary Outcome Measure Information:
Title
Hemagglutination Inhibition (HI) titer responses to vaccine and circulating strains of influenza
Description
A subset of volunteers may participate it in this outcome.
Time Frame
Baseline to 21-35 days post vaccine
Title
Pseudovirion neutralization (PVN) responses to vaccine and circulating strains of influenza
Description
A subset of volunteers may participate it in this outcome.
Time Frame
Baseline to 21-35 days post vaccine
Title
Anti-Neuraminidase (Anti-NA) titer responses to vaccine and circulating strains of influenza
Description
A subset of volunteers may participate it in this outcome.
Time Frame
Baseline to 21-35 days post vaccine
Title
Cellular Responses: Frequency of antigen specific CD4 and CD8 cells, B cells
Description
A subset of volunteers may participate it in this outcome.
Time Frame
Baseline to 21-35 days post vaccine
Title
Rate of Influenza-like Illness
Time Frame
Onset > 13 days after vaccination up to 1 year
Title
Frequency of influenza confirmed hospitalization
Time Frame
Onset > 13 days after vaccination up to 1 year
Title
Number of duty (work) days lost due to Influenza-like Illness
Time Frame
Onset > 13 days after vaccination up to 1 year
Other Pre-specified Outcome Measures:
Title
Tertiary Arm- Assess the burden of covid-19 and explore the inter-relationship between influenza and covid-19
Description
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)
Time Frame
onset >13 days after vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Eligible for care in Department of Defense medical facilities (Defense Enrollment Eligibility Reporting System eligible) ≥18 years of age. At a participating Military Treatment Facility site for the purpose of receiving a seasonal (2018-2019, 2019-2020,2020-2021, 2021-2022) influenza vaccination. Able to speak English and able to provide informed consent Able to receive and respond to texts and/or emails, or a military recruit Exclusion Criteria: Adults intending to receive or who have received the current seasons FluMist Vaccine (LAIV) Adults who have already received a flu vaccine within the current season Individual who cannot receive a flu vaccine or standard dosing due to another medical condition Allergic to gentamicin, polymyxin and/or neomycin Individuals who fail to meet the inclusion criteria
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Burgess, MD
Organizational Affiliation
Uniformed Services University of the Health Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rhonda Colombo, MD
Organizational Affiliation
Infectious Diseases Clinical Research Program
Official's Role
Study Director
Facility Information:
Facility Name
Naval Medical Center San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
34800
Country
United States
Facility Name
United States Naval Academy
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21402
Country
United States
Facility Name
USU
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20307
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Facility Name
Womack Army Medical Center
City
Fort Bragg
State/Province
North Carolina
ZIP/Postal Code
28310
Country
United States
Facility Name
Brooke Army Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Lackland Airforce Base
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78243
Country
United States
Facility Name
Naval Medical Center Portsmouth
City
Portsmouth
State/Province
Virginia
ZIP/Postal Code
23704
Country
United States
Facility Name
Madigan Army Medical Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98431
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Investigative team members with knowledge and experience with statistical and scientific procedures will de-identify PHI and prepare the data set to be shared.
Citations:
PubMed Identifier
26085551
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.
Results Reference
background
PubMed Identifier
29447141
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.
Results Reference
background
PubMed Identifier
29109276
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.
Results Reference
background
PubMed Identifier
29059230
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.
Results Reference
background
PubMed Identifier
24667168
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.
Results Reference
background
PubMed Identifier
29471464
Citation
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.
Results Reference
background
PubMed Identifier
18722473
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.
Results Reference
background
PubMed Identifier
20153374
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.
Results Reference
background
Links:
URL
https://www.cdc.gov/flu/index.htm
Description
Influenza. Centers for Disease Control and Prevention

Learn more about this trial

A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

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