Trial Outcomes & Findings for A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (NCT NCT03734237)

NCT ID: NCT03734237

Last Updated: 2023-11-24

Results Overview

Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE4
• Target enrollment: 15449 participants
• Primary outcome timeframe: Onset > 13 days after vaccination up to 1 year
• Results posted on: 2023-11-24

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 15449 enrolled participants, 17 were excluded from analysis due to ineligibility (i.e., not eligible for care in MHS, already received an influenza vaccination, etc).

Participant milestones

Measure	Egg-based Vaccine Subjects vaccinated with egg-based vaccine.	Recombinant Vaccine Subjects vaccinated with recombinant vaccine.	Cell-derived Vaccine Subjects vaccinated with cell-derived vaccine.
Overall Study STARTED	5145	5150	5137
Overall Study COMPLETED	5137	5138	5127
Overall Study NOT COMPLETED	8	12	10

Reasons for withdrawal

Measure	Egg-based Vaccine Subjects vaccinated with egg-based vaccine.	Recombinant Vaccine Subjects vaccinated with recombinant vaccine.	Cell-derived Vaccine Subjects vaccinated with cell-derived vaccine.
Overall Study Lost to Follow-up	1	3	0
Overall Study Withdrawal by Subject	7	9	10

Baseline Characteristics

A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Baseline characteristics by cohort

Measure	Egg-based Vaccine n=5145 Participants Subjects vaccinated with egg-based vaccine.	Recombinant Vaccine n=5150 Participants Subjects vaccinated with Recombinant vaccine.	Cell-derived Vaccine n=5137 Participants Subjects vaccinated with Cell-derived vaccine.	Total n=15432 Participants Total of all reporting groups
Age, Customized < 65 years	4944 Participants n=5 Participants	4954 Participants n=7 Participants	4947 Participants n=5 Participants	14845 Participants n=4 Participants
Age, Customized >=65 years	201 Participants n=5 Participants	196 Participants n=7 Participants	190 Participants n=5 Participants	587 Participants n=4 Participants
Sex: Female, Male Female	1635 Participants n=5 Participants	1672 Participants n=7 Participants	1649 Participants n=5 Participants	4956 Participants n=4 Participants
Sex: Female, Male Male	3510 Participants n=5 Participants	3478 Participants n=7 Participants	3488 Participants n=5 Participants	10476 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	995 Participants n=5 Participants	984 Participants n=7 Participants	955 Participants n=5 Participants	2934 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4025 Participants n=5 Participants	4048 Participants n=7 Participants	4051 Participants n=5 Participants	12124 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	125 Participants n=5 Participants	118 Participants n=7 Participants	131 Participants n=5 Participants	374 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	51 Participants n=5 Participants	49 Participants n=7 Participants	44 Participants n=5 Participants	144 Participants n=4 Participants
Race (NIH/OMB) Asian	289 Participants n=5 Participants	315 Participants n=7 Participants	316 Participants n=5 Participants	920 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	48 Participants n=5 Participants	63 Participants n=7 Participants	50 Participants n=5 Participants	161 Participants n=4 Participants
Race (NIH/OMB) Black or African American	600 Participants n=5 Participants	643 Participants n=7 Participants	606 Participants n=5 Participants	1849 Participants n=4 Participants
Race (NIH/OMB) White	3575 Participants n=5 Participants	3504 Participants n=7 Participants	3546 Participants n=5 Participants	10625 Participants n=4 Participants
Race (NIH/OMB) More than one race	281 Participants n=5 Participants	270 Participants n=7 Participants	284 Participants n=5 Participants	835 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	301 Participants n=5 Participants	306 Participants n=7 Participants	291 Participants n=5 Participants	898 Participants n=4 Participants
Region of Enrollment United States	5145 Participants n=5 Participants	5150 Participants n=7 Participants	5137 Participants n=5 Participants	15432 Participants n=4 Participants

PRIMARY outcome

Timeframe: Onset > 13 days after vaccination up to 1 year

Population: Analysis based on actual vaccine received.

Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.

Outcome measures

Measure	Egg-based Vaccine n=5145 Participants Subjects vaccinated with egg-based vaccine.	Cell-derived Vaccine n=5137 Participants Subjects vaccinated with cell-derived vaccine.	Recombinant Vaccine n=5150 Participants Subjects vaccinated with recombinant vaccine.
Number of Participants With Laboratory Confirmed Influenza	68 participants	86 participants	77 participants

SECONDARY outcome

Timeframe: Baseline to 21-35 days post vaccine

Population: 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=359 Participants Subjects vaccinated with cell-derived vaccine.	Recombinant Vaccine n=373 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	158 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 vaccine

Neutralizing 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 egg-passaged HA-pseudovirus (SGP/19/16 NIB-104)	8.7 percentage of participants	13.9 percentage of participants	47.1 percentage of participants
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

SECONDARY outcome

Timeframe: Baseline to 21-35 days post vaccine

Anti-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=32 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, Post-vaccination	291.5 geometric mean titer Interval 216.0 to 393.2	230.5 geometric mean titer Interval 150.6 to 352.9	78.4 geometric mean titer Interval 63.4 to 96.9
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine. N1 Titer, Pre-vaccination	53.7 geometric mean titer Interval 41.1 to 70.1	121.2 geometric mean titer Interval 78.9 to 186.1	80.7 geometric mean titer Interval 58.4 to 111.5
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine. N1 Titer, Post-vaccination	207.1 geometric mean titer Interval 146.6 to 292.6	118.3 geometric mean titer Interval 76.9 to 182.1	77.7 geometric mean titer Interval 56.8 to 106.2
Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine. N2 Titer, Pre-vaccination	121.2 geometric mean titer Interval 94.3 to 156.0	126.0 geometric mean titer Interval 82.7 to 191.8	83.0 geometric mean titer Interval 67.6 to 102.0

SECONDARY outcome

Timeframe: Onset > 13 days after vaccination up to 1 year

Rate of protocol defined influenza-like illness ascertained by participant response to active surveillance.

Outcome measures

Measure	Egg-based Vaccine n=5145 Participants Subjects vaccinated with egg-based vaccine.	Cell-derived Vaccine n=5150 Participants Subjects vaccinated with cell-derived vaccine.	Recombinant Vaccine n=5137 Participants Subjects vaccinated with recombinant vaccine.
Number of Participants With Influenza-Like Illness	1055 Participants	1120 Participants	1080 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Onset > 13 days after influenza vaccination up until one year

Population: 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=4604 Participants Subjects vaccinated with egg-based vaccine.	Cell-derived Vaccine n=4614 Participants Subjects vaccinated with cell-derived vaccine.	Recombinant Vaccine n=4592 Participants Subjects vaccinated with recombinant vaccine.
Number of Participants With SARS-CoV-2 and Influenza Co-Infection SC2 Status	131 Participants	157 Participants	141 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 year

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.

Outcome measures

Measure	Egg-based Vaccine n=131 Participants Subjects vaccinated with egg-based vaccine.	Cell-derived Vaccine n=157 Participants Subjects vaccinated with cell-derived vaccine.	Recombinant Vaccine n=141 Participants Subjects vaccinated with recombinant vaccine.
Symptom Severity of SARS CoV2	1.00 score on a scale Interval 0.7 to 1.4	1.10 score on a scale Interval 0.7 to 1.5	1.10 score on a scale Interval 0.7 to 1.5

Adverse Events

Egg-based Vaccine

Serious events: 9 serious events

Other events: 0 other events

Deaths: 1 deaths

Recombinant Vaccine

Serious events: 5 serious events

Other events: 0 other events

Deaths: 1 deaths

Cell-derived Vaccine

Serious events: 6 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Measure	Egg-based Vaccine n=5145 participants at risk Subjects vaccinated with egg-based vaccine.	Recombinant Vaccine n=5150 participants at risk Subjects vaccinated with recombinant vaccine.	Cell-derived Vaccine n=5137 participants at risk Subjects vaccinated with cell-derived vaccine.
General disorders Hospitalization	0.10% 5/5145 • From study enrollment up to one year.	0.02% 1/5150 • From study enrollment up to one year.	0.04% 2/5137 • From study enrollment up to one year.
Infections and infestations Hospitalization	0.02% 1/5145 • From study enrollment up to one year.	0.06% 3/5150 • From study enrollment up to one year.	0.06% 3/5137 • From study enrollment up to one year.
Respiratory, thoracic and mediastinal disorders Hospitalization	0.02% 1/5145 • From study enrollment up to one year.	0.02% 1/5150 • From study enrollment up to one year.	0.00% 0/5137 • From study enrollment up to one year.
Cardiac disorders Hospitalization	0.04% 2/5145 • From study enrollment up to one year.	0.00% 0/5150 • From study enrollment up to one year.	0.00% 0/5137 • From study enrollment up to one year.
Renal and urinary disorders Hospitalization	0.00% 0/5145 • From study enrollment up to one year.	0.00% 0/5150 • From study enrollment up to one year.	0.02% 1/5137 • From study enrollment up to one year.
Surgical and medical procedures Hospitalization	0.02% 1/5145 • From study enrollment up to one year.	0.00% 0/5150 • From study enrollment up to one year.	0.00% 0/5137 • From study enrollment up to one year.

Other adverse events

Adverse event data not reported

Additional Information

Timothy Burgess, MD, MPH

USUHS

Phone: (301) 295-9792

Email: timothy.burgess@usuhs.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place