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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05110911




Registration number
NCT05110911
Ethics application status
Date submitted
27/10/2021
Date registered
8/11/2021

Titles & IDs
Public title
Does Repeat Influenza Vaccination Constrain Influenza Immune Responses and Protection
Scientific title
Does Repeat Influenza Vaccination Constrain Influenza Immune Responses and Protection
Secondary ID [1] 0 0
1R01AI41534
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza, Human 0 0
SARS-CoV-2 Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Treatment: Other - Influenza vaccination: Fluarix Tetra, Vaxigrip Tetra, Fluquadri, Fluad Quad, Afluia Quad, Flucelvax Quad
Treatment: Other - SARS-CoV-2 vaccination: Comirnaty or Vaxzevria

Healthcare Workers - Eligible participants will be recruited from 1 of 6 participating hospitals in Australia and will meet the following criteria: personnel (including staff, honorary staff, students and volunteers) located at a participating hospital or healthcare service at the time of recruitment who would be eligible for the hospital's free vaccination programme; be aged =18 years old and =60 years old; have a mobile phone that can receive and send SMS messages; willing and able to provide blood samples; available for follow-up over the next 7 months; able and willing to complete the informed consent process.

There are no restrictions on the type of healthcare worker (HCW) that can be recruited into the study in terms of their job role. HCW will be any hospital staff, including clinical, research, administrative and support staff.


Treatment: Other: Influenza vaccination: Fluarix Tetra, Vaxigrip Tetra, Fluquadri, Fluad Quad, Afluia Quad, Flucelvax Quad
Influenza vaccine made available to healthcare workers at the participating healthcare sites, as part of their free vaccination campaigns for healthcare workers.

Treatment: Other: SARS-CoV-2 vaccination: Comirnaty or Vaxzevria
SARS-CoV-2 vaccine made available to healthcare workers at the participating healthcare sites, as part of their free vaccination campaigns for healthcare workers.

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Seropositivity post-vaccination (influenza vaccine)
Timepoint [1] 0 0
Post-vaccination blood draws are at 14-21 days post vaccination. Collected each year 2020-2023 post annual influenza vaccination.
Primary outcome [2] 0 0
Seropositivity post-season (influenza vaccine)
Timepoint [2] 0 0
End of the season blood draws are in October or November each year, at the conclusion of Australia's annual influenza season. Vaccination usually occurs in April or May. Collected each year 2020-2023 post annual influenza season.
Primary outcome [3] 0 0
Fold-rise in geometric mean antibody titre (GMT) pre- to post-vaccination
Timepoint [3] 0 0
Changes from day 0 to day 14-21 post influenza vaccination. Collected each year 2020-2023 pre and post annual influenza vaccination.
Primary outcome [4] 0 0
Fold-change in geometric mean antibody titre (GMT) post-vaccination to post-season
Timepoint [4] 0 0
Changes from day 14-21 to post-season. Influenza season in Australia is approximately May to November. Pre-vaccination to post-season is approximately April or May to October or November each year. Collected each year 2020-2023.
Primary outcome [5] 0 0
Seroconversion fraction post-vaccination
Timepoint [5] 0 0
Changes from day 0 to day 14-21 post influenza vaccination. Collected each year 2020-2023 pre and post annual influenza vaccination.
Secondary outcome [1] 0 0
Healthcare workers (HCWs) PCR-positive for influenza at the end of each season
Timepoint [1] 0 0
Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.
Secondary outcome [2] 0 0
Influenza attack rate at the end of each season
Timepoint [2] 0 0
Person-time at risk, during influenza season. Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.
Secondary outcome [3] 0 0
Vaccine efficacy (VE)
Timepoint [3] 0 0
Person-time at risk, during influenza season. Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.
Secondary outcome [4] 0 0
Duration of illness (influenza)
Timepoint [4] 0 0
Days ill, during influenza season. Influenza season in Australia is approximately May to November. Follow up for PCR-positives from approximately April/May to October/November each year from 2020-2023.
Secondary outcome [5] 0 0
Haemagglutinin (HA) antibody landscapes for vaccine-naïve and highly-vaccinated healthcare workers (HCWs)
Timepoint [5] 0 0
Bloods on day 0, day 7, day 14-21 post influenza vaccination and end of season. Collected each year 2020-2023 pre and post annual influenza vaccination and end of influenza season.
Secondary outcome [6] 0 0
Haemagglutinin (HA) antibody landscapes for infected versus uninfected healthcare workers (HCWs)
Timepoint [6] 0 0
Bloods on day 7 and day 14-21 post influenza infection. Collected each year 2020-2023 along with pre and post annual influenza vaccination and end of influenza season bloods.
Secondary outcome [7] 0 0
Enumeration of cells
Timepoint [7] 0 0
Bloods on day 0 and day 14-21 post influenza vaccination and post infection. The key indicator is the frequency of these B cells on day 14 post-vaccination relative to pre-vaccination frequencies. Collected each year 2020-2023.
Secondary outcome [8] 0 0
B cells
Timepoint [8] 0 0
Blood draws on day 7 post influenza vaccination and post infection. Collected each year 2020-2023.
Secondary outcome [9] 0 0
Quantify biological mechanisms that shape the antibody response
Timepoint [9] 0 0
Bloods on day 0, day 7, day 14-21 post influenza vaccination, day 7, day 14-21 post infection and end of season. Collected each year 2020-2023.
Secondary outcome [10] 0 0
Estimate protective titres
Timepoint [10] 0 0
Bloods on day 0, day 7, day 14-21 post influenza vaccination, day 7, day 14-21 post infection and end of season. Collected each year 2020-2023.
Secondary outcome [11] 0 0
Optimal influenza vaccination strategy for healthcare workers (HCWs) under different vaccine availability
Timepoint [11] 0 0
Bloods on day 0, day 7, day 14-21 post influenza vaccination, day 7, day 14-21 post infection and end of season. Collected each year 2020-2023.
Secondary outcome [12] 0 0
Estimated SARS-CoV-2 attack rates among symptomatic and asymptomatic healthcare workers (HCWs)
Timepoint [12] 0 0
Follow-up period 2020-2023.
Secondary outcome [13] 0 0
Case-hospitalization risk
Timepoint [13] 0 0
Follow-up period 2020-2023.
Secondary outcome [14] 0 0
Risk factors for asymptomatic, mild and severe SARS-CoV-2 infection
Timepoint [14] 0 0
Follow-up period 2020-2023.
Secondary outcome [15] 0 0
Estimated SARS-CoV-2 antibody titre associated with protection
Timepoint [15] 0 0
Follow-up period 2020-2023.
Secondary outcome [16] 0 0
Estimated SARS-CoV-2 antibody kinetics over time
Timepoint [16] 0 0
Bloods on day 3, day 7, day 14-21, day 30 post infection and end of season. Daily swabs during symptomatic infection to two days post resolution of symptoms. Follow-up period 2020-2023.
Secondary outcome [17] 0 0
Identification of key behavioural drivers of transmission
Timepoint [17] 0 0
Follow-up period 2020-2023.
Secondary outcome [18] 0 0
Estimated duration of viral shedding and viral load in SARS-CoV-2 infection over time
Timepoint [18] 0 0
During symptomatic infection to two days post resolution of symptoms. Follow-up period 2020-2023.
Secondary outcome [19] 0 0
Enumeration of SARS-CoV-2-reactive B and T cells and identification of dominant epitopes
Timepoint [19] 0 0
Bloods on day 3, day 7, day 14-21, day 30 post infection and end of season. Follow-up period 2020-2023.
Secondary outcome [20] 0 0
Gene expression
Timepoint [20] 0 0
Changes from day 0 to day 7 post vaccination. Follow-up period 2020-2023.
Secondary outcome [21] 0 0
Enumeration of SARS-CoV-2-reactive B and T cells induced by each vaccine formulation
Timepoint [21] 0 0
Specific B and T cells detected at day 14-21 post vaccine schedule completion versus day 0. Follow-up period 2020-2023.
Secondary outcome [22] 0 0
Seroconversion of SARS-CoV-2 serum antibody titres induced by each vaccine formulation
Timepoint [22] 0 0
At day 14-21 post vaccine schedule completion. Follow-up period 2020-2023.
Secondary outcome [23] 0 0
Fold changes in innate immune cells and in vaccine specific B and T cells
Timepoint [23] 0 0
Vaccine specific B and T cells detected at day 14-21 post vaccine schedule completion versus day 0. Follow-up period 2020-2023.
Secondary outcome [24] 0 0
Comparison of antibody (and B and T cell) responses induced against COVID-19 and influenza vaccines among participants who received COVID-19 versus influenza vaccine first or who were co-administered both vaccines.
Timepoint [24] 0 0
Antibody levels will be correlated with fold changes in innate immune cells and in vaccine specific B and T cells detected at day 14-21 post vaccine schedule completion versus day 0. Follow-up period 2020-2023.

Eligibility
Key inclusion criteria
Eligible participants will be recruited from 1 of 6 participating hospitals and will meet the following criteria:

* Personnel (including staff, honorary staff, students and volunteers) located at a participating hospital or healthcare service at the time of recruitment who would be eligible for the hospital's free vaccination programme
* Be aged =18 years old and =60 years old;
* Have a mobile phone that can receive and send SMS messages;
* Willing and able to provide blood samples;
* Available for follow-up over the next 7 months;
* Able and willing to complete the informed consent process.

There are no restrictions on the type of healthcare worker (HCW) that can be recruited into the study in terms of their job role. HCWs can be any hospital staff, including clinical, research, administrative and support staff.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Immunosuppressive treatment (including systemic corticosteroids) within the past 6 months;
* Personnel for whom vaccination is contraindicated at the time of recruitment.

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital - Adelaide
Recruitment hospital [5] 0 0
The Alfred - Melbourne
Recruitment hospital [6] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 0 0
5006 - Adelaide
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of Queensland
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Sydney Children's Hospitals Network
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
The Alfred
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Adelaide
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
The University of Western Australia
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
London School of Hygiene and Tropical Medicine
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
University of Newcastle, Australia
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sheena Sullivan, MPH, PhD
Address 0 0
University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sheena Sullivan, MPH, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 3 9342 9317
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Sharing original data: The proposed study will collect demographic and clinical information, as well as blood and respiratory specimens from participants. Because we will be conducting longitudinal follow-up, we will be collecting identifiable information. Any data shared will be stripped of identifiers prior to release for sharing. However, there remains the possibility of deductive disclosure of participants with unusual characteristics. Thus, data will only be shared with new collaborators under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Analytic code
When will data be available (start and end dates)?
Data will be available after publication of results, likely in late-2024.
Available to whom?
Data will only be shared with new collaborators under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://hcwflustudy.com/home