ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000079347

Ethics application status

Approved

Date submitted

8/01/2017

Date registered

16/01/2017

Date last updated

13/08/2019

Date data sharing statement initially provided

3/07/2019

Date results information initially provided

3/07/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

South Australian Meningococcal B Vaccine Herd Immunity Study in Adolescents

Scientific title

A cluster randomised controlled trial to assess the impact of meningococcal B vaccine 4CMenB on nasopharyngeal carriage of N. Meningitidis in adolescents in South Australia

Secondary ID [1]

ClinicalTrials.gov Identifier: NCT03089086

Universal Trial Number (UTN)

Trial acronym

B Part of It

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Invasive Meningococcal disease

Neisseria meningitides nasopharyngeal carriage

Condition category

Condition code

Infection

Studies of infection and infectious agents

Public Health

Epidemiology

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Group A - 2017
Students within schools randomised to group A will receive two doses of 0.5ml of the licensed 4CMenB vaccine administered by intramuscular injection in 2017, with an interval of 1-2 months between doses, as per the Australian Technical Advisory Group on Immunisation recommendations. An oropharyngeal swab will be collected at baseline and at 12 months.

Group B - 2018
Students within schools randomised to group B will receive two doses of 0.5ml of the licensed 4CMenB vaccine administered by intramuscular injection in 2018, with an interval of 1-2 months between doses. Following completion of baseline and 12 month oropharyngeal swab.

Intervention code [1]

Prevention

Comparator / control treatment

Group B - 2018
Students within schools randomised to group B will receive the licensed 4CMenB vaccine following completion of baseline and 12 month oropharyngeal swab in 2018.

Control group

Active

Outcomes

Primary outcome [1]

Prevalence of all disease causing genogroups of N. meningitidis (A, B, C, W, X, Y) as measured by PCR at 12 months in vaccinated and unvaccinated year 10 and 11 school students.

Timepoint [1]

One year after baseline visit

Secondary outcome [1]

Prevalence of each N. meningitidis genogroup (A, B, C, W, X, Y) as measured by PCR at the 12 month pharyngeal swab in vaccinated and unvaccinated year 10 and 11 high school students.

Timepoint [1]

One year after baseline visit

Secondary outcome [2]

Prevalence of all N. meningitidis genogroups as measured by PCR at the 12 month pharyngeal swabs in vaccinated and unvaccinated year 10 and 11 school students

Timepoint [2]

One year after baseline visit

Secondary outcome [3]

Acquisition of disease causing N. meningitidis (A, B, C, W, X, Y) genogroups (negative at baseline, positive at 12 month followup) as measured by PCR in vaccinated and unvaccinated year 10 and 11 school students.

Timepoint [3]

One year after baseline visit

Secondary outcome [4]

Acquisition of all N. meningitidis as measured by PCR in vaccinated and unvaccinated year 10 and 11 school students.

Timepoint [4]

12 months

Secondary outcome [5]

Risk factors associated with carriage prevalence of disease causing N. meningitidis at baseline and 12 months. Risk factors were collected using a study-specific questionnaire.

Timepoint [5]

Baseline and 12 months

Secondary outcome [6]

Risk factors associated with carriage prevalence of all N. meningitidis at baseline and 12 months. Risk factors were collected using a study-specific questionnaire.

Timepoint [6]

baseline and 12 months

Eligibility

Key inclusion criteria

1. South Australian secondary school students in years 10, 11, and 12 in 2017
2. Written parental consent for those under the age of 18
3. Written student consent-assent for those under the age of 18 (or if 18 years old and older consent for themselves)
4. Available at school for at least the first pharyngeal swab

Minimum age

14 Years

Maximum age

100 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Previous recipient of 4CMenB vaccine (Bexsero)
2. Known pregnancy
3. Anaphylaxis following any component of the 4CMenB vaccine

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation concealment by central randomisation by computer (Adelaide Health Technology Assessment)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomisation at two stages using computer software. Stratified allocation (school size, education sector and SES) following school agreement to participate.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Randomisation occurs at the school level.. Randomisation will occur in two stages; stage 1 randomisation of schools that agree to participate and are schools associated with large councils (to facilitate program delivery), stage 2 randomisation of remaining schools once consent forms have been returned. Students at schools randomised to receive the vaccine at baseline will receive the 4CMenB vaccine in 2017. Students at schools randomised to receive the vaccine at the 12 month posterior pharyngeal swab will receive the 4CMenB vaccine in 2018.

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

All analyses will be undertaken according to a pre-specified statistical analysis plan. Students with available outcome data will be analysed according to the randomised group of their school (intention to treat principle). A sensitivity per-protocol analysis of the primary outcome will also be conducted in vaccine group students that followed a 2 dose schedule of 4CMenB and control group students that did not receive 4CMenB before the 12 month follow-up.

The primary outcome of carriage of N. meningitidis at 12 months (yes/no) will be compared between groups using logistic regression, with generalized estimating equations used to account for clustering at the school level. The difference in carriage between groups will be expressed as an odds ratio with 95% confidence interval. Adjustment will be made for baseline carriage, randomisation strata (school size, ICSEA) and other baseline variables pre-specified for adjustment.

Missing data on the primary outcome will be addressed using multiple imputation. All secondary outcomes will be compared between groups using logistic regression models, with generalized estimating equations used to account for clustering due to school. In planned sub-group analyses of the primary and secondary outcomes, the effect of the 4CMenB vaccine will also be examined separately for metropolitan and rural schools, and year 10 and year 11 students. Effect modification by these factors will be assessed separately by including an interaction term involving randomised group within each statistical model.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/02/2017

Actual

3/04/2017

Date of last participant enrolment

Anticipated

30/06/2017

Actual

30/06/2017

Date of last data collection

Anticipated

30/06/2019

Actual

31/12/2018

Sample size

Target

44000

Accrual to date

Final

34489

Recruitment in Australia

Recruitment state(s)

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

GlaxoSmithKline Biologicals S.A.

Address [1]

Rue d I'Institut 89, 1330 Rixensart

Country [1]

Belgium

Primary sponsor type

University

Name

The University of Adelaide

Address

Robinson Research Institute and Adelaide Medical School
Discipline of Paediatrics
Women's & Children's Hospital
Level 2 Clarence Reiger Building
72 King William Road
North Adelaide SA 5006

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

None

Country [1]

Other collaborator category [1]

Government body

Name [1]

SA Health

Address [1]

Citi Centre
11 Hindmarsh Square
Adelaide SA 5000

Country [1]

Australia

Other collaborator category [2]

Hospital

Name [2]

Women's and Children's Health Network

Address [2]

Women's and Children's Hospital
72 king William Rd
North Adelaide
SA 5006

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Women's and Children's Health Network (WCHN) Human Research Ethics Committee's (HREC) Women's and Children's Health Network (WCHN) Human Research Ethics Committee's (HREC)

Ethics committee address [1]

Research Secretariat
Women's and Children's Health Network
72 King William Road
North Adelaide SA 5006

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

02/11/2016

Ethics approval number [1]

HREC/16/WCHN/140

Summary

Brief summary

To estimate the effect on carriage, all year 10, 11, and 12 students will be offered 4CMenB
vaccination in South Australia through schools over the study period with 50% of the
students enrolled receiving the vaccine in 2017 and 50% in 2018. In year 10 and 11
students, posterior pharyngeal swabs will be obtained at baseline and 12 months post
baseline to estimate the difference in carriage prevalence of all genogroups of N.
meningitidis between vaccinated and unvaccinated participants.

Trial website

www.bpartofit.com.au

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Helen Marshall

Address

Vaccinology & Immunology Research Trials Unit
Women's and Children's Hospital
Level 2 Clarence Reiger Building
72 King William Road
North Adelaide SA 5006

Country

Australia

Phone

+ 61 (0)8 8161 8115

Fax

+ 61 (0)8 81617031

[email protected]

Contact person for public queries

Name

Ms Kathryn Riley

Address

Vaccinology & Immunology Research Trials Unit
Women's and Children's Hospital
Level 2 Clarence Reiger Building
72 King William Road
North Adelaide SA 5006

Country

Australia

Phone

+61 8 8161 6328

Fax

+61 (0)8 8161 7031

[email protected]

Contact person for scientific queries

Name

Prof Helen Marshall

Address

Vaccinology & Immunology Research Trials Unit
Women's and Children's Hospital
Level 2 Clarence Reiger Building
72 King William Road
North Adelaide SA 5006

Country

Australia

Phone

+61 (0)8 8161 8115

Fax

+61 (0)8 8161 7031

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

De-identified; individual participant data underlying published results only.

When will data be available (start and end dates)?

We estimate the data will be available from the start of 2021 for approximately 12 months.

Available to whom?

IPD will be made available on a case-by-case basis at the discretion of the International Scientific Advisory Committee and WCHN HREC.

Available for what types of analyses?

Achieve the aims in the approved proposal.

How or where can data be obtained?

[email protected]

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
2472	Study protocol			[email protected]
2473	Statistical analysis plan			[email protected]

Results publications and other study-related documents

Documents added manually

Current Study Results

No documents have been uploaded by study researchers.

Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
4641	Study results article	Yes		Marshall HS, McMillan M, Koehler AP, Lawrence A, S... [More Details]	371948-(Uploaded-02-02-2021-10-35-07)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Meningococcal group B vaccine for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B.	2019	https://dx.doi.org/10.2147/IDR.S159952
Embase	B Part of It protocol: A cluster randomised controlled trial to assess the impact of 4CMenB vaccine on pharyngeal carriage of Neisseria meningitidis in adolescents.	2018	https://dx.doi.org/10.1136/bmjopen-2017-020988

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically