Influenza, HumanPhase 4TROPICS1NCT02655874
Tropical Influenza Control Strategies for the Elderly
A Phase 4 study testing Influenza vaccine and Tetanus-diphtheria-pertussis vaccine in people with Influenza, Human, run by Tan Tock Seng Hospital at 1 site in Singapore.
Trial summary
TROPICS1 is a randomized, observer-blind, active comparator-controlled, single-center, Phase IV trial in 200 participants aged ≥65 years. The control group will receive a standard dose licensed trivalent inactivated influenza vaccine at day 1, and an active-comparator (Tetanus-diphtheria-pertussis vaccine) at day 180. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Influenza vaccine and Tetanus-diphtheria-pertussis vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteSingapore
- Study dates
- May 2016to Oct 2017
- 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 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Age ≥65 years on the day of inclusion
- No influenza vaccination in the previous 10 months
- No tetanus, diphtheria or pertussis vaccine in the previous 1 year
- No virologically confirmed influenza infection in the previous 10 months
- Able to provide written informed consent
- Able to attend all scheduled visits and comply with all trial procedures
Who cannot join
- Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another trial investigating a vaccine, drug, medical device, or medical procedure
- History of a life threatening reaction to the vaccine used in the trial, or to a vaccine containing any of the same substances
- Known systemic hypersensitivity to any of the vaccine components, including:
- Egg protein (eggs or egg products)
- Chicken products
- Formaldehyde
Show all 17Show fewer
- Neomycin or kanamycin
- Octoxinol 9 (Triton X-100)
- Cetyltrimethylammonium bromide (CTAB)
- History of Guillain-Barré syndrome (GBS) within 6 weeks following previous influenza vaccination
- Acute respiratory infection on the day of enrolment
- Moderate or severe acute illness/infection (according to investigator judgement) on the day of vaccination, or febrile illness (temperature ≥ 37.5°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
- Self-reported thrombocytopenia, contraindicating Intramuscular vaccination
- Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding six months; or long-term systemic corticosteroid therapy (prednisolone ≥ 7.5mg/day or equivalent for more than 2 consecutive weeks within the past 3 months)
- Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
- Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator
Trial locations and contacts
1 site in 1 country.
Singapore1 site
Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital
Singapore
About this study
Official title: A Single-centre, Randomised, Observer-blind, Active Comparator-controlled, Superiority Trial of the Immune Response to Six-monthly Versus Annual Standard Dose Inactivated Trivalent Influenza Vaccination in the Elderly
TROPICS1 is a randomized, observer-blind, active comparator-controlled, single-center, Phase IV trial in 200 participants aged ≥65 years. The control group will receive a standard dose licensed trivalent inactivated influenza vaccine at day 1, and an active-comparator (Tetanus-diphtheria-pertussis vaccine) at day 180. Participants in the experimental group will receive the same influenza vaccine at day 1 and day 180. Endpoints are immunological, and include measures of haemagglutination-inhibition (HI) titres, micro-neutralisation titres and cell-mediated immunity at 4 time points after the initial vaccination up to Day 360. The primary hypothesis is that participants receiving an influenza booster at day 180 will achieve superior influenza seroprotection (HI titre ≥1:40) at day 208, compared to controls.
The World Health Organization (WHO) estimates the global annual burden from seasonal influenza as 1 billion infections, with 3-5 million severe cases and 300,000-500,000 deaths. The pattern and impact of these infections varies considerably with climate. In temperate countries, influenza epidemics characteristically occur during the cold winter months, while in sub-tropical countries, they coincide with the rainy seasons. Closer to the equator, influenza virus activity is more complex. In Singapore, biannual epidemics are usual, but with continuous transmission year-round. Bi-annual epidemics, tri-annual epidemics and year round virus activity have also been described in other tropical countries, from Indonesia and Malaysia to Peru and Mexico.
There is no published data reporting year-round influenza vaccine effectiveness in the elderly from countries with continuous influenza virus activity. Despite numerous studies worldwide exploring the HI antibody response to influenza vaccination, the majority of these do not continue follow up beyond seroconversion (21-28 days). However, of the few available, HI antibody titres declined following influenza vaccination in the elderly, such that within 6-12 months geometric mean titres approached pre-vaccination levels. With biannual epidemics and year-round transmission in tropical regions, year-round seroprotection may be important to reduce influenza infections in this environment. A six-monthly vaccination cycle would correspond with the decline in vaccine-induced seroprotection in the elderly, and the 6-monthly periodicity of outbreaks in Singapore and other tropical countries.
- Conditions
- Influenza, Human
- Being tested
- Influenza vaccine, Tetanus-diphtheria-pertussis vaccine
- Keywords
- Seasonal Influenza, Antibody response, Influenza Vaccines, Hemagglutination Inhibition, Elderly, immunosenescence, Tropics
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Influenza vaccineBiological
Administered at day 1
Influenza vaccineBiological
Administered at day 180
Tetanus-diphtheria-pertussis vaccineBiological
Administered at day 180
| Study group | Role | What they receive |
|---|---|---|
| Six-monthly influenza vaccine | Experimental | Standard dose trivalent inactivated seasonal influenza vaccine will be administered at day 1 and 180 Receives: Biological: Influenza vaccine |
| Annual influenza vaccine | Active comparator | Standard dose trivalent inactivated seasonal influenza vaccine will be administered at day 1 and an active-comparator (Tetanus-diphtheria-pertussis) at day 180 Receives: Biological: Influenza vaccine; Biological: Tetanus-diphtheria-pertussis vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine)
Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine.
Measured: Day 208 post-vaccination
Secondary outcomes (10)
Geometric mean titres
Comparison by vaccination group of Geometric mean titres (GMTs) post-primary vaccination against homologous and heterologous influenza strains to those present in the administered influenza vaccine.
Measured: Day 208 to 360 post-vaccination
Geometric mean ratio
Comparison by vaccination group of the Geometric mean ratio (GMR) post-primary vaccination against homologous and heterologous influenza strains to those present in the administered influenza vaccine.
Measured: Day 208 to 360 post-vaccination
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine)
Comparison by vaccination group of the proportion of subjects with HI titre ≥1:40 (1/dil) at day 360 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine.
Measured: Day 360 post-vaccination
Seroconversion (Proportion of subjects achieving seroconversion after vaccination for each of the influenza strains present in the administered influenza vaccine)
Comparison by vaccination group of the proportion of subjects achieving seroconversion after vaccination for each of the influenza strains present in the administered influenza vaccine. Seroconversion is defined as a pre-vaccination HI titre < 1:10 and a post vaccination titre ≥1:40, or a pre-vaccination titre > 1:10 and a minimum fourfold rise in HI titre.
Measured: Day 208 to 360 post-vaccination
Micro-neutralization titres
Comparison by vaccination group of Micro-neutralization titres post-primary vaccination against strains present in the administered influenza vaccine.
Measured: Day 208 to 360 post-vaccination
Influenza-like illness
Comparison by vaccination group of the number of subjects reporting an influenza-like illness
Measured: Day 208 to 360 post-vaccination
Influenza infection
Comparison by vaccination group of the number of subjects with PCR confirmed influenza infection
Measured: Day 208 to 360 post-vaccination
Healthcare utilization
Comparison by vaccination group of the number of subjects reporting healthcare utilization. This is defined as unscheduled physician visits, emergency room visits and hospitlizations.
Measured: Day 180 to 360 post-vaccination
Solicited and unsolicited adverse events
Frequency and severity of solicited local (injection site) and systemic adverse events for 7 days post-vaccination
Measured: Day 1 to 7 and day 180 to 187
Serious adverse events
A serious adverse event is defined as any untoward medical occurrence that is an important event.
Measured: Day 1 to 28, and day 180 to 208
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2016 (estimated)
- Study startMay 2016
- Primary completionJun 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Influenza, HumanStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tan Tock Seng Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Healthcare Group, Singapore
- Responsible party
- Sponsor
- Investigators
- Barnaby Young, Principal investigator, Tan Tock Seng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02655874
- Sponsor's protocol ID
- 2015/01047
- Other IDs
- 2015
- Acronym
- TROPICS1
- Status last verified
- Nov 2017
- First submitted
- 12 Jan 2016
- Last updated
- 14 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Young B, Sadarangani S, Haur SY, Yung CF, Barr I, Connolly J, Chen M, Wilder-Smith A. Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator-controlled, Randomized Superiority Trial. Clin Infect Dis. 2019 Jun 18;69(1):121-129. doi: 10.1093/cid/ciy836.
PubMed 30277500Young B, Sadarangani S, Yew HS, Yung CF, Leo YS, Chen MI, Wilder-Smith A. The immune response to 6-monthly versus annual standard dose inactivated trivalent influenza vaccination in older people: study protocol for a randomised clinical trial. Trials. 2017 Feb 10;18(1):67. doi: 10.1186/s13063-017-1808-8.
PubMed 28183326
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-centre, Randomised, Observer-blind, Active Comparator-controlled, Superiority Trial of the Immune Response to Six-monthly Versus Annual Standard Dose Inactivated Trivalent Influenza Vaccination in the Elderly
- ClinicalTrials.gov ID
- NCT02655874
- Acronym / sponsor ID
- TROPICS1 / 2015/01047
- Conditions
- Influenza, Human
- Keywords
- Seasonal Influenza, Antibody response, Influenza Vaccines, Hemagglutination Inhibition, Elderly, immunosenescence, Tropics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Tan Tock Seng HospitalUniversity, hospital or other
- Collaborators
- National Healthcare Group, Singapore
- Study start
- May 2016 (actual)
- Primary completion
- Jun 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 14 Jan 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.
TROPICS1 is a randomized, observer-blind, active comparator-controlled, single-center, Phase IV trial in 200 participants aged ≥65 years. The control group will receive a standard dose licensed trivalent inactivated influenza vaccine at day 1, and an active-comparator (Tetanus-diphtheria-pertussis vaccine) at day 180. Participants in the experimental group will receive the same influenza vaccine at day 1 and day 180. Endpoints are immunological, and include measures of haemagglutination-inhibition (HI) titres, micro-neutralisation titres and cell-mediated immunity at 4 time points after the initial vaccination up to Day 360. The primary hypothesis is that participants receiving an influenza booster at day 180 will achieve superior influenza seroprotection (HI titre ≥1:40) at day 208, compared to controls.
The World Health Organization (WHO) estimates the global annual burden from seasonal influenza as 1 billion infections, with 3-5 million severe cases and 300,000-500,000 deaths. The pattern and impact of these infections varies considerably with climate. In temperate countries, influenza epidemics characteristically occur during the cold winter months, while in sub-tropical countries, they coincide with the rainy seasons. Closer to the equator, influenza virus activity is more complex. In Singapore, biannual epidemics are usual, but with continuous transmission year-round. Bi-annual epidemics, tri-annual epidemics and year round virus activity have also been described in other tropical countries, from Indonesia and Malaysia to Peru and Mexico.
There is no published data reporting year-round influenza vaccine effectiveness in the elderly from countries with continuous influenza virus activity. Despite numerous studies worldwide exploring the HI antibody response to influenza vaccination, the majority of these do not continue follow up beyond seroconversion (21-28 days). However, of the few available, HI antibody titres declined following influenza vaccination in the elderly, such that within 6-12 months geometric mean titres approached pre-vaccination levels. With biannual epidemics and year-round transmission in tropical regions, year-round seroprotection may be important to reduce influenza infections in this environment. A six-monthly vaccination cycle would correspond with the decline in vaccine-induced seroprotection in the elderly, and the 6-monthly periodicity of outbreaks in Singapore and other tropical countries.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Six-monthly influenza vaccine | Experimental | Biological: Influenza vaccineStandard dose trivalent inactivated seasonal influenza vaccine will be administered at day 1 and 180 |
| Annual influenza vaccine | Active comparator | Biological: Influenza vaccine, Biological: Tetanus-diphtheria-pertussis vaccineStandard dose trivalent inactivated seasonal influenza vaccine will be administered at day 1 and an active-comparator (Tetanus-diphtheria-pertussis) at day 180 |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (6 listed)
- Age ≥65 years on the day of inclusion
- No influenza vaccination in the previous 10 months
- No tetanus, diphtheria or pertussis vaccine in the previous 1 year
- No virologically confirmed influenza infection in the previous 10 months
- Able to provide written informed consent
Key exclusion criteria (17 listed)
- Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another trial investigating a vaccine, drug, medical device, or medical procedure
- History of a life threatening reaction to the vaccine used in the trial, or to a vaccine containing any of the same substances
- Known systemic hypersensitivity to any of the vaccine components, including:
- History of Guillain-Barré syndrome (GBS) within 6 weeks following previous influenza vaccination
- Acute respiratory infection on the day of enrolment
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 |
|---|---|---|
| Influenza vaccineAdministered at day 1 | Biological | Annual influenza vaccine, Six-monthly influenza vaccine |
| Influenza vaccineAdministered at day 180 | Biological | Six-monthly influenza vaccine |
| Tetanus-diphtheria-pertussis vaccineAdministered at day 180 | Biological | Annual influenza vaccine |
Primary outcome
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine)
Time frame: Day 208 post-vaccination
Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine.
10 secondary outcomes
Geometric mean titres
Time frame: Day 208 to 360 post-vaccination
Geometric mean ratio
Time frame: Day 208 to 360 post-vaccination
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine)
Time frame: Day 360 post-vaccination
Seroconversion (Proportion of subjects achieving seroconversion after vaccination for each of the influenza strains present in the administered influenza vaccine)
Time frame: Day 208 to 360 post-vaccination
Micro-neutralization titres
Time frame: Day 208 to 360 post-vaccination
Influenza-like illness
Time frame: Day 208 to 360 post-vaccination
Influenza infection
Time frame: Day 208 to 360 post-vaccination
Healthcare utilization
Time frame: Day 180 to 360 post-vaccination
Solicited and unsolicited adverse events
Time frame: Day 1 to 7 and day 180 to 187
Serious adverse events
Time frame: Day 1 to 28, and day 180 to 208
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 14 Nov 2017.
- Derived from this study: PubMed 30277500Young B, Sadarangani S, Haur SY, Yung CF, Barr I, Connolly J, Chen M, Wilder-Smith A. Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator-controlled, Randomized Superiority Trial. Clin Infect Dis. 2019 Jun 18;69(1):121-129. doi: 10.1093/cid/ciy836.
- Derived from this study: PubMed 28183326Young B, Sadarangani S, Yew HS, Yung CF, Leo YS, Chen MI, Wilder-Smith A. The immune response to 6-monthly versus annual standard dose inactivated trivalent influenza vaccination in older people: study protocol for a randomised clinical trial. Trials. 2017 Feb 10;18(1):67. doi: 10.1186/s13063-017-1808-8.
- 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.
Barnaby Young principal investigator
Tan Tock Seng Hospital
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 Influenza vaccine and Tetanus-diphtheria-pertussis vaccine in people with Influenza, Human, run by Tan Tock Seng Hospital at 1 site in Singapore.
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 6 inclusion and 17 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 14 Nov 2017. 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 Singapore. 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?
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine) (time frame: Day 208 post-vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02655874, which also lists 2 linked publications.
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 14 Nov 2017.