InfluenzaPhase 4RIVERNCT03598439
Randomized Influenza Vaccine Evaluation of Immune Response
A Phase 4 study testing Standard IIV4, Recombinant and Cell-culture in people with Influenza, run by Marshfield Clinic Research Foundation at 1 site in United States.
Trial summary
Licensed influenza vaccines are manufactured with a variety of technologies. The majority are split, inactivated vaccines derived from egg-adapted, high growth reassortant viruses. Two US licensed products do not use egg-adapted viruses: Flucelvax (mammalian cell culture) and FluBlok (recombinant). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Influenza
- What is being tested?
- Standard IIV4, Recombinant and Cell-culture
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 366 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2018to 9 Jul 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18-64 years
- Marshfield Clinic patients living in or around Marshfield, Wisconsin since July 2015
- Willing and able to give informed consent and comply with study requirements
Who cannot join
- Receipt of 2018-19 influenza vaccine prior to study enrollment
- Known to be pregnant at the time of enrollment
- Current participation or plans to participate in another clinical trial involving an experimental agent
- Presence of a contraindication to influenza vaccination
- Plans to relocate outside the geographic location in the next two years
Trial locations and contacts
1 site in 1 country.
United States1 site
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449
About this study
Official title: Randomized Open-Label Trial to Compare Immunogenicity of Egg-Based and Non-Egg Based Quadrivalent Influenza Vaccines Among Adults 18-64 Years of Age (US Flu Vaccine Effectiveness Serologic Study, 2018-19 and 2019-20)
Licensed influenza vaccines are manufactured with a variety of technologies. The majority are split, inactivated vaccines derived from egg-adapted, high growth reassortant viruses. Two US licensed products do not use egg-adapted viruses: Flucelvax (mammalian cell culture) and FluBlok (recombinant). There is increasing evidence that egg propagation induces virus mutations that impair the immune responses to circulating viruses. However, the impact of egg-propagation on clinical vaccine effectiveness is uncertain, and there is no preferential recommendation for any specific influenza vaccine product or technology. A direct comparison of serologic response to egg based and non-egg based vaccines in adults has not been performed. This randomized trial will compare serologic responses to the egg- and non-egg A(H3N2) vaccine component. The study cohort will be followed for two influenza seasons to evaluate sequential vaccination effects on immune response.
- Conditions
- Influenza
- Being tested
- Standard IIV4, Recombinant, Cell-culture
- Keywords
- influenza vaccine, adults, Immune response
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard IIV4Biological
Also called Flulaval Quadrivalent
Standard inactivated influenza vaccine
RecombinantBiological
Also called FluBlok Quadrivalent
Influenza vaccine that uses a hemagglutinin protein manufactured in insect cells with a baculovirus vector
Cell-cultureBiological
Also called Flucelvax Quadrivalent
inactivated influenza vaccine manufactured using mammalian cell lines; current vaccine uses a cell-propagated H3N2 strain.
| Study group | Role | What they receive |
|---|---|---|
| Recombinant (RIV4) Influenza Vaccine | Experimental | A single dose of licensed recombinant influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20. Receives: Biological: Recombinant |
| Cell-culture (ccIIV4) Influenza Vaccine | Experimental | A single dose of licensed cell-culture influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20 Receives: Biological: Cell-culture |
| Standard (IIV4) Influenza Vaccine | Active comparator | A single dose of licensed standard influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20. Receives: Biological: Standard IIV4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-vaccination titer
geometric mean titers (as measured by microneutralization) to cell-grown A(H3N2) vaccine reference virus
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start30 Jul 2018
- Primary completion18 Mar 2020
- Study completion9 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 366 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marshfield Clinic Research Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Huong Nguyen, PhD, Marshfield Clinic Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03598439
- Sponsor's protocol ID
- MCL10218
- Acronym
- RIVER
- Status last verified
- Nov 2025
- First submitted
- 16 Jul 2018
- Last updated
- 21 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Open-Label Trial to Compare Immunogenicity of Egg-Based and Non-Egg Based Quadrivalent Influenza Vaccines Among Adults 18-64 Years of Age (US Flu Vaccine Effectiveness Serologic Study, 2018-19 and 2019-20)
- ClinicalTrials.gov ID
- NCT03598439
- Acronym / sponsor ID
- RIVER / MCL10218
- Conditions
- Influenza
- Keywords
- influenza vaccine, adults, Immune response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 366 participants (actual)
- Lead sponsor
- Marshfield Clinic Research FoundationUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- 30 Jul 2018 (actual)
- Primary completion
- 18 Mar 2020 (actual)
- Study completion
- 9 Jul 2024 (actual)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Licensed influenza vaccines are manufactured with a variety of technologies. The majority are split, inactivated vaccines derived from egg-adapted, high growth reassortant viruses. Two US licensed products do not use egg-adapted viruses: Flucelvax (mammalian cell culture) and FluBlok (recombinant). There is increasing evidence that egg propagation induces virus mutations that impair the immune responses to circulating viruses. However, the impact of egg-propagation on clinical vaccine effectiveness is uncertain, and there is no preferential recommendation for any specific influenza vaccine product or technology. A direct comparison of serologic response to egg based and non-egg based vaccines in adults has not been performed. This randomized trial will compare serologic responses to the egg- and non-egg A(H3N2) vaccine component. The study cohort will be followed for two influenza seasons to evaluate sequential vaccination effects on immune response.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Recombinant (RIV4) Influenza Vaccine | Experimental | Biological: RecombinantA single dose of licensed recombinant influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20. |
| Cell-culture (ccIIV4) Influenza Vaccine | Experimental | Biological: Cell-cultureA single dose of licensed cell-culture influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20 |
| Standard (IIV4) Influenza Vaccine | Active comparator | Biological: Standard IIV4A single dose of licensed standard influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Aged 18-64 years
- Marshfield Clinic patients living in or around Marshfield, Wisconsin since July 2015
- Willing and able to give informed consent and comply with study requirements
Key exclusion criteria (5 listed)
- Receipt of 2018-19 influenza vaccine prior to study enrollment
- Known to be pregnant at the time of enrollment
- Current participation or plans to participate in another clinical trial involving an experimental agent
- Presence of a contraindication to influenza vaccination
- Plans to relocate outside the geographic location in the next two years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard IIV4Also: Flulaval QuadrivalentStandard inactivated influenza vaccine | Biological | Standard (IIV4) Influenza Vaccine |
| RecombinantAlso: FluBlok QuadrivalentInfluenza vaccine that uses a hemagglutinin protein manufactured in insect cells with a baculovirus vector | Biological | Recombinant (RIV4) Influenza Vaccine |
| Cell-cultureAlso: Flucelvax Quadrivalentinactivated influenza vaccine manufactured using mammalian cell lines; current vaccine uses a cell-propagated H3N2 strain. | Biological | Cell-culture (ccIIV4) Influenza Vaccine |
Primary outcome
Post-vaccination titer
Time frame: 28 days
geometric mean titers (as measured by microneutralization) to cell-grown A(H3N2) vaccine reference virus
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Standard IIV4, Recombinant and Cell-culture in people with Influenza, run by Marshfield Clinic Research Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-vaccination titer (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.