Influenza, HumanPhase 4RETAINNCT02957890
Immunogenicity of Twice-annual Influenza Vaccination in Older Adults in Hong Kong
A Phase 4 study testing Inactivated influenza vaccine (NH formulation) and Inactivated influenza vaccine (SH formulation) in people with Influenza, Human, run by The University of Hong Kong at 1 site in China.
Trial summary
This study evaluates the immunogenicity of adding inactivated influenza vaccine with southern hemisphere (SH) formulation to standard once-annual influenza vaccination with northern hemisphere (NH) formulation in older adults in Hong Kong over 9 years. Read more about this study
- Who is it for?
- Ages 70 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Inactivated influenza vaccine (NH formulation) and Inactivated influenza vaccine (SH formulation)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 1 siteChina
- Study dates
- 18 Nov 2016to Sep 2026
- 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 70 to 79 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Adult aged 70-79 years attending GOPCs, DECCs or day care centres for receiving influenza vaccination or medical or preventive care visits.
Who cannot join
- Individuals who show signs of dementia (either confirmed by medical records or do not pass the Mini-cog test) or significant cognitive impairment and are not competent to give their consent.
- Individuals who report medical conditions not suitable to receive inactivated influenza vaccines, such as:
- Severe allergic reaction (e.g., anaphylaxis) after previous dose of any influenza vaccine; or to a vaccine component, including egg protein;
- Moderate or severe acute illness with or without fever after any previous influenza vaccination; or
- A history of Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination.
- Individuals, according to medical record, who report medical conditions not suitable to receive intramuscular injection, such as:
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- bleeding disorders
- habitually taking anticoagulants (with the exception of antiplatelets such as aspirin).
- Individuals who have any medical conditions not suitable to receive inactivated influenza vaccines as determined by a clinician.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Immunogenicity of Twice-annual Vaccination Against Seasonal Influenza for Two Hemispheres in Older Adults in Hong Kong - a Randomised Controlled Trial
This study evaluates the immunogenicity of adding inactivated influenza vaccine with southern hemisphere (SH) formulation to standard once-annual influenza vaccination with northern hemisphere (NH) formulation in older adults in Hong Kong over 9 years. Half of participants will receive twice-annual influenza vaccination with NH and SH formulation, while the other half will receive once-annual influenza vaccination with NH formulation and a placebo.
Read the detailed description
Background: Hong Kong is located in subtropical regions with two seasonal peaks of influenza transmission. North Hemisphere seasonal influenza vaccine is usually available for vaccination by general public starting in October every year before the anticipated winter peak starting in December in Hong Kong, and it presumably also provides protection against the same prevailing strains during summer peak starting around July of the next year. However, influenza vaccines may have poorer efficacy and effectiveness in older adults. The investigators hypothesize that in a subtropical or tropical location with prolonged circulation of influenza viruses, including the emergence of new strains at different times of the year, twice-annual vaccination with the latest available strains could provide the best protection.
Aim: To test the immune profiles over time of older adults following twice-annual influenza vaccination against those receiving once-annual influenza vaccination.
Design and subjects: An immunogenicity study with a randomized placebo-controlled design among 400 older adults aged 70-79 years. The investigators will enroll participants from the general community who attend general outpatient clinics for influenza vaccination or medical or preventive care visits. Eligible individuals will be randomly allocated in equal proportions to two intervention groups (I: once-annual standard inactivated influenza vaccine; II: twice-annual standard inactivated influenza vaccine) consisting of ten rounds of vaccination as designated by the intervention group before each winter/summer influenza season and followed throughout the 5 years. *In August 2021 we extended the study for a further 4 years (9 years in total) through to August 2025, with the same study design.* Before each summer influenza season those in group II will receive the inactivated influenza vaccine with the southern hemisphere formulation and the other group will receive saline placebo. For each round of vaccination (or placebo), blood samples for immunological tests will be collected before administration and 30 days after administration among all participants, and at 7, 30 and 91 days after administration in a subset of 25% of the participants. Acute illnesses among participants will be monitored by active surveillance during influenza seasons. The vaccine formulations in each round of vaccination will be updated for each season according to WHO recommendations.
Main outcome measures: Antibody titres measured by haemagglutination-inhibition assays, which is an established correlate of protection, in addition to other measurements on humoral and cell-mediated immune responses in the two intervention groups each round.
- Conditions
- Influenza, Human
- Being tested
- Inactivated influenza vaccine (NH formulation), Inactivated influenza vaccine (SH formulation), Placebo
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inactivated influenza vaccine (NH formulation)Biological
Round 1 (November): 0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation
Inactivated influenza vaccine (SH formulation)Biological
Round 2 (May): 0.5mL Vaxigrip®, Sanofi Pasteur, containing 45μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the southern hemisphere formulation
PlaceboBiological
Round 2 (May): 0.5mL normal saline
| Study group | Role | What they receive |
|---|---|---|
| Twice-annual influenza vaccination | Experimental | Twice-annual influenza vaccination: administrations of inactivated influenza vaccine (Northern hemisphere formulation, NH) prior to the northern hemisphere winter, plus inactivated influenza vaccine (Southern hemisphere formulation, SH) prior to the northern hemisphere summer. Receives: Biological: Inactivated influenza vaccine (NH formulation); Biological: Inactivated influenza vaccine (SH formulation) |
| Once-annual influenza vaccination | Placebo comparator | Administrations of inactivated influenza vaccine (Northern hemisphere formulation, NH) prior to the northern hemisphere winter, plus placebo prior to the northern hemisphere summer. Receives: Biological: Inactivated influenza vaccine (NH formulation); Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in antibody titres
The difference in antibody titres of participants measured by haemagglutination-inhibition (HAI) assay, evaluated by (1) the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days, and (2) the geometric mean titre (GMT) ratios between the two groups against each of the vaccine strains at 30 days and 182 days. (The targeted rise in antibody titre is defined as the percentage of subjects with either a pre-vaccination HAI titre <10 and a post-vaccination HAI titre ≥40, or a pre-vaccination HAI titre ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titre.)
Measured: 30 and 182 days after each vaccination
Secondary outcomes (4)
Seroprotection
The proportion of participants who achieve seroprotection defined as an HAI titre ≥40 after each vaccination
Measured: 30 days after each vaccination
CMI responses
The vaccine-induced influenza-specific CD4+ and CD8+ T cell responses 7 days post- vaccination, proxy by anti-viral IFNγ production evaluated by Intracellular Cytokine Staining (ICS) assay. Responses for these and other relevant biomarkers are compared to baseline at the time of vaccination.
Measured: 7 days after each vaccination
Adverse events
The rate of adverse events within 30 days after vaccination
Measured: 30 days after each vaccination
PCR confirmed infection
The rate of PCR-confirmed influenza virus infection between each vaccination
Measured: 182 days after each vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2016 (estimated)
- Study start18 Nov 2016
- Primary completionSep 2025 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza, HumanStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, Hospital Authority, Hong Kong
- Responsible party
- Principal investigator, Dr. Benjamin John Cowling, The University of Hong Kong
- Investigators
- Benjamin COWLING, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02957890
- Sponsor's protocol ID
- YHT004.5
- Acronym
- RETAIN
- Status last verified
- Dec 2023
- First submitted
- 31 Oct 2016
- Last updated
- 11 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity of Twice-annual Vaccination Against Seasonal Influenza for Two Hemispheres in Older Adults in Hong Kong - a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT02957890
- Acronym / sponsor ID
- RETAIN / YHT004.5
- Conditions
- Influenza, Human
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, Hospital Authority, Hong Kong
- Study start
- 18 Nov 2016 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 8 Nov 2016 (estimated)
- 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.
This study evaluates the immunogenicity of adding inactivated influenza vaccine with southern hemisphere (SH) formulation to standard once-annual influenza vaccination with northern hemisphere (NH) formulation in older adults in Hong Kong over 9 years. Half of participants will receive twice-annual influenza vaccination with NH and SH formulation, while the other half will receive once-annual influenza vaccination with NH formulation and a placebo.
Detailed description
Background: Hong Kong is located in subtropical regions with two seasonal peaks of influenza transmission. North Hemisphere seasonal influenza vaccine is usually available for vaccination by general public starting in October every year before the anticipated winter peak starting in December in Hong Kong, and it presumably also provides protection against the same prevailing strains during summer peak starting around July of the next year. However, influenza vaccines may have poorer efficacy and effectiveness in older adults. The investigators hypothesize that in a subtropical or tropical location with prolonged circulation of influenza viruses, including the emergence of new strains at different times of the year, twice-annual vaccination with the latest available strains could provide the best protection.
Aim: To test the immune profiles over time of older adults following twice-annual influenza vaccination against those receiving once-annual influenza vaccination.
Design and subjects: An immunogenicity study with a randomized placebo-controlled design among 400 older adults aged 70-79 years. The investigators will enroll participants from the general community who attend general outpatient clinics for influenza vaccination or medical or preventive care visits. Eligible individuals will be randomly allocated in equal proportions to two intervention groups (I: once-annual standard inactivated influenza vaccine; II: twice-annual standard inactivated influenza vaccine) consisting of ten rounds of vaccination as designated by the intervention group before each winter/summer influenza season and followed throughout the 5 years. *In August 2021 we extended the study for a further 4 years (9 years in total) through to August 2025, with the same study design.* Before each summer influenza season those in group II will receive the inactivated influenza vaccine with the southern hemisphere formulation and the other group will receive saline placebo. For each round of vaccination (or placebo), blood samples for immunological tests will be collected before administration and 30 days after administration among all participants, and at 7, 30 and 91 days after administration in a subset of 25% of the participants. Acute illnesses among participants will be monitored by active surveillance during influenza seasons. The vaccine formulations in each round of vaccination will be updated for each season according to WHO recommendations.
Main outcome measures: Antibody titres measured by haemagglutination-inhibition assays, which is an established correlate of protection, in addition to other measurements on humoral and cell-mediated immune responses in the two intervention groups each round.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Twice-annual influenza vaccination | Experimental | Biological: Inactivated influenza vaccine (NH formulation), Biological: Inactivated influenza vaccine (SH formulation)Twice-annual influenza vaccination: administrations of inactivated influenza vaccine (Northern hemisphere formulation, NH) prior to the northern hemisphere winter, plus inactivated influenza vaccine (Southern hemisphere formulation, SH) prior to the northern hemisphere summer. |
| Once-annual influenza vaccination | Placebo comparator | Biological: Inactivated influenza vaccine (NH formulation), Biological: PlaceboAdministrations of inactivated influenza vaccine (Northern hemisphere formulation, NH) prior to the northern hemisphere winter, plus placebo prior to the northern hemisphere summer. |
Who may qualify
- Ages
- 70 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- Adult aged 70-79 years attending GOPCs, DECCs or day care centres for receiving influenza vaccination or medical or preventive care visits.
Key exclusion criteria (9 listed)
- Individuals who show signs of dementia (either confirmed by medical records or do not pass the Mini-cog test) or significant cognitive impairment and are not competent to give their consent.
- Individuals who report medical conditions not suitable to receive inactivated influenza vaccines, such as:
- Individuals, according to medical record, who report medical conditions not suitable to receive intramuscular injection, such as:
- Individuals who have any medical conditions not suitable to receive inactivated influenza vaccines as determined by a clinician.
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 |
|---|---|---|
| Inactivated influenza vaccine (NH formulation)Round 1 (November): 0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation | Biological | Once-annual influenza vaccination, Twice-annual influenza vaccination |
| Inactivated influenza vaccine (SH formulation)Round 2 (May): 0.5mL Vaxigrip®, Sanofi Pasteur, containing 45μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the southern hemisphere formulation | Biological | Twice-annual influenza vaccination |
| PlaceboRound 2 (May): 0.5mL normal saline | Biological | Once-annual influenza vaccination |
Primary outcome
Difference in antibody titres
Time frame: 30 and 182 days after each vaccination
The difference in antibody titres of participants measured by haemagglutination-inhibition (HAI) assay, evaluated by (1) the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days, and (2) the geometric mean titre (GMT) ratios between the two groups against each of the vaccine strains at 30 days and 182 days. (The targeted rise in antibody titre is defined as the percentage of subjects with either a pre-vaccination HAI titre <10 and a post-vaccination HAI titre ≥40, or a pre-vaccination HAI titre ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titre.)
4 secondary outcomes
Seroprotection
Time frame: 30 days after each vaccination
CMI responses
Time frame: 7 days after each vaccination
Adverse events
Time frame: 30 days after each vaccination
PCR confirmed infection
Time frame: 182 days after each vaccination
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2023.
- Individual participant dataSharing planned: Yes
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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.
Benjamin COWLING, PhD principal investigator
The University of Hong Kong
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 Inactivated influenza vaccine (NH formulation) and Inactivated influenza vaccine (SH formulation) in people with Influenza, Human, run by The University of Hong Kong at 1 site in China.
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 1 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 11 Dec 2023. 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 China. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
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?
Difference in antibody titres (time frame: 30 and 182 days after each vaccination). 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 11 Dec 2023.