Trial Outcomes & Findings for A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (NCT NCT03734237)
NCT ID: NCT03734237
Last Updated: 2026-04-02
Results Overview
Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE4
Target enrollment
15448 participants
Primary outcome timeframe
Onset > 13 days after vaccination up to 1 year
Results posted on
2026-04-02
Participant Flow
Participants were recruited from adult military health system (MHS) beneficiaries preparing to receive a seasonal influenza vaccination at a participating DoD site. Eligible participants who provided informed consent were block randomized 1:1:1 to receive one of three types of licensed influenza vaccines (cell-culture-based vaccine, recombinant vaccine, or egg-derived vaccine). The first participant was enrolled in November 2018, and the last participant was enrolled in January 2022.
Among 15448 enrolled participants, 16 were excluded from analysis due to ineligibility (i.e., not eligible for care in MHS, already received an influenza vaccination, etc.)
Participant milestones
| Measure |
Recombinant Vaccine
Subjects vaccinated with recombinant vaccine.
|
Cell-derived Vaccine
Subjects vaccinated with cell-derived vaccine.
|
Egg-based Vaccine
Subjects vaccinated with egg-based vaccine.
|
|---|---|---|---|
|
Overall Study
STARTED
|
5154
|
5130
|
5148
|
|
Overall Study
COMPLETED
|
5142
|
5119
|
5139
|
|
Overall Study
NOT COMPLETED
|
12
|
11
|
9
|
Reasons for withdrawal
| Measure |
Recombinant Vaccine
Subjects vaccinated with recombinant vaccine.
|
Cell-derived Vaccine
Subjects vaccinated with cell-derived vaccine.
|
Egg-based Vaccine
Subjects vaccinated with egg-based vaccine.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
12
|
11
|
9
|
Baseline Characteristics
A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD
Baseline characteristics by cohort
| Measure |
Egg-based Vaccine
n=5148 Participants
Subjects vaccinated with egg-based vaccine.
|
Recombinant Vaccine
n=5154 Participants
Subjects vaccinated with Recombinant vaccine.
|
Cell-derived Vaccine
n=5130 Participants
Subjects vaccinated with Cell-derived vaccine.
|
Total
n=15432 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
< 65 years
|
4948 Participants
n=5 Participants
|
4957 Participants
n=5 Participants
|
4940 Participants
n=10 Participants
|
14845 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
200 Participants
n=5 Participants
|
197 Participants
n=5 Participants
|
190 Participants
n=10 Participants
|
587 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1639 Participants
n=5 Participants
|
1673 Participants
n=5 Participants
|
1644 Participants
n=10 Participants
|
4956 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3509 Participants
n=5 Participants
|
3481 Participants
n=5 Participants
|
3486 Participants
n=10 Participants
|
10476 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
997 Participants
n=5 Participants
|
987 Participants
n=5 Participants
|
951 Participants
n=10 Participants
|
2935 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4026 Participants
n=5 Participants
|
4049 Participants
n=5 Participants
|
4050 Participants
n=10 Participants
|
12125 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
125 Participants
n=5 Participants
|
118 Participants
n=5 Participants
|
129 Participants
n=10 Participants
|
372 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
51 Participants
n=5 Participants
|
49 Participants
n=5 Participants
|
44 Participants
n=10 Participants
|
144 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
289 Participants
n=5 Participants
|
315 Participants
n=5 Participants
|
316 Participants
n=10 Participants
|
920 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
48 Participants
n=5 Participants
|
63 Participants
n=5 Participants
|
50 Participants
n=10 Participants
|
161 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
601 Participants
n=5 Participants
|
642 Participants
n=5 Participants
|
606 Participants
n=10 Participants
|
1849 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3579 Participants
n=5 Participants
|
3509 Participants
n=5 Participants
|
3538 Participants
n=10 Participants
|
10626 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
280 Participants
n=5 Participants
|
270 Participants
n=5 Participants
|
285 Participants
n=10 Participants
|
835 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
300 Participants
n=5 Participants
|
306 Participants
n=5 Participants
|
291 Participants
n=10 Participants
|
897 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5148 Participants
n=5 Participants
|
5154 Participants
n=5 Participants
|
5130 Participants
n=10 Participants
|
15432 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Onset > 13 days after vaccination up to 1 yearPopulation: Analysis based on actual vaccine received.
Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.
Outcome measures
| Measure |
Egg-based Vaccine
n=5148 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=5130 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=5154 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Number of Participants With Laboratory Confirmed Influenza
|
69 participants
|
87 participants
|
79 participants
|
SECONDARY outcome
Timeframe: Baseline to 21-35 days post vaccinePopulation: Substudy participants were included if they had pre- and post-vaccination samples.
Strain-specific seroconversion rate determined by reference hemagglutination inhibition assay.
Outcome measures
| Measure |
Egg-based Vaccine
n=355 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=357 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=375 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.
H1N1: Number with 4-fold rise in HI
|
103 participants
|
114 participants
|
184 participants
|
|
Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.
H3N2: Number with 4-fold rise in HI
|
108 participants
|
157 participants
|
267 participants
|
|
Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.
B-Victoria: Number with 4-fold rise in HI
|
49 participants
|
48 participants
|
92 participants
|
|
Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.
B-Yamagata: Number with 4-fold rise in HI
|
19 participants
|
24 participants
|
64 participants
|
SECONDARY outcome
Timeframe: Baseline to 21-35 days post vaccineNeutralizing antibody responses (4-fold rise) to HA-psuedoviruses corresponding to vaccine-matched viruses, recently circulating influenza virus, and emerging influenza strain.
Outcome measures
| Measure |
Egg-based Vaccine
n=46 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=36 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=51 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
Seroconversion rate against cell-passaged HA-pseudovirus (NC/04/16)
|
8.7 percentage of participants
|
8.3 percentage of participants
|
43.1 percentage of participants
|
|
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
Seroconversion rate against wild-type (SGP/19/16; recombinant HA-pseudovirus)
|
4.3 percentage of participants
|
16.7 percentage of participants
|
56.9 percentage of participants
|
|
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
Seroconversion rate against HA-pseudovirus corresponding to prior season vaccine strain
|
6.5 percentage of participants
|
13.9 percentage of participants
|
62.7 percentage of participants
|
|
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
Seroconversion rate against HA-pseudovirus corresponding to recently circulating virus
|
4.3 percentage of participants
|
11.1 percentage of participants
|
52.9 percentage of participants
|
|
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
Seroconversion rate against HA-pseudovirus corresponding to emerging infuenza strain
|
2.2 percentage of participants
|
0 percentage of participants
|
21.6 percentage of participants
|
|
Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.
Seroconversion rate against egg-passaged HA-pseudovirus (SGP/19/16 NIB-104)
|
8.7 percentage of participants
|
13.9 percentage of participants
|
47.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to 21-35 days post vaccineAnti-Neuraminidase (Anti-NA) titer responses determined by enzyme linked immuno-assay.
Outcome measures
| Measure |
Egg-based Vaccine
n=46 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=35 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=51 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.
N2 Titer, Pre-vaccination
|
121 geometric mean titer
Interval 93.6 to 157.1
|
123 geometric mean titer
Interval 82.2 to 182.7
|
83.0 geometric mean titer
Interval 67.6 to 102.0
|
|
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.
N2 Titer, Post-vaccination
|
292 geometric mean titer
Interval 214.3 to 396.5
|
226 geometric mean titer
Interval 150.4 to 338.7
|
78.4 geometric mean titer
Interval 63.4 to 96.9
|
|
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.
N1 Titer, Pre-vaccination
|
54 geometric mean titer
Interval 40.8 to 70.6
|
111 geometric mean titer
Interval 72.7 to 168.0
|
80.7 geometric mean titer
Interval 58.4 to 111.5
|
|
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.
N1 Titer, Post-vaccination
|
207 geometric mean titer
Interval 145.2 to 295.4
|
109 geometric mean titer
Interval 72.3 to 163.5
|
77.7 geometric mean titer
Interval 56.8 to 106.2
|
SECONDARY outcome
Timeframe: Onset > 13 days after vaccination up to 1 yearRate of protocol defined influenza-like illness ascertained by participant response to active surveillance.
Outcome measures
| Measure |
Egg-based Vaccine
n=5148 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=5154 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=5130 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Number of Participants With Influenza-Like Illness
|
1054 Participants
|
1121 Participants
|
1078 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Onset > 13 days after influenza vaccination up until one yearPopulation: Participants enrolled in PAIVED beginning in 2019-20 season.
Laboratory-confirmed SARS CoV2, and SARS CoV2 plus influenza co-infection, as ascertained by nasal swab PCR.
Outcome measures
| Measure |
Egg-based Vaccine
n=4607 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=4614 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=4589 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Number of Participants With SARS-CoV-2 and Influenza Co-Infection
SC2 Status
|
131 Participants
|
159 Participants
|
140 Participants
|
|
Number of Participants With SARS-CoV-2 and Influenza Co-Infection
Influenza/SC2 Coinfection Status
|
0 Participants
|
1 Participants
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: onset >13 days after Influenza vaccination up to 1 yearSymptom 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.
Outcome measures
| Measure |
Egg-based Vaccine
n=131 Participants
Subjects vaccinated with egg-based vaccine.
|
Cell-derived Vaccine
n=159 Participants
Subjects vaccinated with cell-derived vaccine.
|
Recombinant Vaccine
n=140 Participants
Subjects vaccinated with recombinant vaccine.
|
|---|---|---|---|
|
Symptom Severity of SARS CoV2
|
1.03 score on a scale
Interval 0.74 to 1.44
|
1.12 score on a scale
Interval 0.68 to 1.5
|
1.11 score on a scale
Interval 0.71 to 1.53
|
Adverse Events
Egg-based Vaccine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Recombinant Vaccine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cell-derived Vaccine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place