Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12615000536561
Ethics application status
Approved
Date submitted
8/05/2015
Date registered
27/05/2015
Date last updated
6/03/2023
Date data sharing statement initially provided
18/02/2019
Date results information initially provided
18/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Australian Study for the Prevention through Immunisation of Cardiovascular Events
Scientific title
Pneumococcal polysaccharide vaccine versus Normal Saline for primary prevention of heart attacks and strokes in at-risk Australians aged 55-60
Secondary ID [1] 286660 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
AUSPICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular Disease 294992 0
Myocardial Infarction 294993 0
Stroke 294994 0
Condition category
Condition code
Public Health 295257 295257 0 0
Epidemiology
Cardiovascular 295258 295258 0 0
Coronary heart disease
Stroke 295259 295259 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
pneumococcal polysaccharide vaccine 0.25mcg(0.5mls) standard dose given intramuscularly at baseline recruitment only
Intervention code [1] 291804 0
Prevention
Comparator / control treatment
normal saline
Control group
Placebo

Outcomes
Primary outcome [1] 295007 0
The primary outcome will be a composite of major CVD events: fatal and non-fatal acute coronary syndrome and ischaemic stroke, ascertained by linkage with AIHW and NDI. The following ICD-10 codes will be included: I20 (unstable angina), I21 (acute myocardial infarction) and I63 (cerebral infarction). Cardiovascular events will be assessed through data linkage to medical records.
Timepoint [1] 295007 0
6 years after randomisation, with interim analysis at 3 years after randomisation
Secondary outcome [1] 314568 0
Myocardial Infarction is assessed through data linkage to in patient medical records (diagnosis by ICD code)
Timepoint [1] 314568 0
5 years after randomisation, with interim analysis at 3 years after randomisation
Secondary outcome [2] 314569 0
Stroke is assessed through data linkage to in patient medical records (diagnosis by ICD code)
Timepoint [2] 314569 0
6 years after randomisation, with interim analysis at 3 years after randomisation

Eligibility
Key inclusion criteria
Men and women aged 55-60 years with no known CVD events and two or more risk factors for CVD. Risk factors include hypercholesterolaemia, hypertension, elevated BMI, and elevated waist circumference.
Minimum age
55 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous pneumococcal vaccination, previous cardiovascular events and any other condition for which the use of the vaccine is indicated (as per the Australian Immunisation Handbook).

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)
There will be a mailout to community dwelling residents in the target age range through the Department of Human Services. Recruitment methods have been expanded to include social media (e.g. Facebook), health and medical websites (e.g. Stroke Foundation), and other means of promotion (e.g. Research Newsletters). Respondents will reply by completing a screening survey to ascertain eligibility by surface mail or via web. Once eligibility criteria are verified again at the clinic, randomisation will be stratified by gender and centre, using a web-based randomization system; allocation will also be concealed by this system as participants will be randomised to group A or B. The study Nurse will draw up the allocated study drug in a room away from the participant. Participants will receive active or control vaccination, the latter being a saline syringe identical in appearance to the vaccine.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
There will be a computer generated randomisation system that will be accessed online. The randomisation will be stratified by each centre.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
The study is a multi-centre trial (6 sites around Australia)
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Due to slow recruitment (3000 over 1 year rather than 6000), the recruitment period was extended to 2 years and 4725 were enrolled and randomised by the end of 2017. In order to accommodate this reduction in the total sample size, power calculations have been modified to reflect 4725 people followed for a longer period, i.e 6 years after the end of recruitment. This should still enable us to detect a HR of 0.84 with 80% power at p=0.05 (two-sided), assuming a similar event rate. To accommodate the longer follow-up period, an interim analysis has been added 3 years after the end of follow-up (median 4 years follow-up). The interim analysis will check the overall event rate in the entire cohort; if this is lower than anticipated in the power calculation, an independent statistical committee will be convened to recommend a revised analysis plan to the steering committee. If the event rate is as anticipated, the follow-up period will continue as planned to 6 years.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
23/02/2016
Actual
23/02/2016
Date of last participant enrolment
Anticipated
31/12/2017
Actual
21/12/2017
Date of last data collection
Anticipated
21/12/2023
Actual
Sample size
Target
4500
Accrual to date
Final
4725
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,WA,VIC
Recruitment hospital [1] 3761 0
Caulfield Hospital - Caulfield
Recruitment hospital [2] 3762 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [3] 3763 0
Gosford Hospital - Gosford
Recruitment hospital [4] 3764 0
The Canberra Hospital - Garran
Recruitment hospital [5] 3796 0
Hunter Medical Research Institute - New Lambton Heights
Recruitment hospital [6] 3797 0
South Australian Health and Medical Research Institute (SAHMRI) - Adelaide
Recruitment postcode(s) [1] 9705 0
3162 - Caulfield
Recruitment postcode(s) [2] 9706 0
6009 - Nedlands
Recruitment postcode(s) [3] 9707 0
2250 - Gosford
Recruitment postcode(s) [4] 9708 0
2605 - Garran
Recruitment postcode(s) [5] 9709 0
2305 - New Lambton Heights
Recruitment postcode(s) [6] 9710 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 291237 0
Government body
Name [1] 291237 0
National Health and Medical Research Council
Country [1] 291237 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
Level 3 The Pod
Hunter Medical Research Institute
1 Kookaburra Ct
New Lambton Heights
New South Wales
2305
Country
Australia
Secondary sponsor category [1] 289912 0
None
Name [1] 289912 0
Address [1] 289912 0
Country [1] 289912 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292796 0
University of Newcastle HREC
Ethics committee address [1] 292796 0
University of Newcastle HREC
Research Services
Research Integrity Unit
The Chancellery
University Drive
University of Newcastle
Callaghan
NSW 2308
Ethics committee country [1] 292796 0
Australia
Date submitted for ethics approval [1] 292796 0
Approval date [1] 292796 0
16/04/2014
Ethics approval number [1] 292796 0
H-2014-0064
Ethics committee name [2] 292801 0
ACT Health HREC
Ethics committee address [2] 292801 0
ACT Health HREC
Building 10
Level 6
Canberra Hospital
PO Box 11
Woden
ACT 2606
Ethics committee country [2] 292801 0
Australia
Date submitted for ethics approval [2] 292801 0
Approval date [2] 292801 0
04/08/2014
Ethics approval number [2] 292801 0
ETH .7.14.177
Ethics committee name [3] 292802 0
NSW Population and Health Services Research Ethics Committee
Ethics committee address [3] 292802 0
NSW Population and Health Services Research Ethics Committee
Level 9
8 Central Avenue
Australian Technology Park
Eveleigh
NSW 2015
Ethics committee country [3] 292802 0
Australia
Date submitted for ethics approval [3] 292802 0
Approval date [3] 292802 0
09/12/2014
Ethics approval number [3] 292802 0
HREC/14/CIPHS/49
Ethics committee name [4] 292803 0
Monash University HREC
Ethics committee address [4] 292803 0
Monash University HREC
Building 3E
Room 111
Clayton Campus
Wellington Road
Clayton
Victoria 3800
Ethics committee country [4] 292803 0
Australia
Date submitted for ethics approval [4] 292803 0
Approval date [4] 292803 0
13/10/2014
Ethics approval number [4] 292803 0
CF14/3016-2014001638
Ethics committee name [5] 292804 0
The University of Western Australia HREC
Ethics committee address [5] 292804 0
The University of Western Australia HREC
Human Ethics
Office of Research Enterprise
The University of Western Australia
MA459
35 Stirling Highway
Crawley
WA 6009
Ethics committee country [5] 292804 0
Australia
Date submitted for ethics approval [5] 292804 0
Approval date [5] 292804 0
03/09/2014
Ethics approval number [5] 292804 0
RA/4/1/7101

Summary
Brief summary
This is a multi-centre trial to investigate the effects of the pneumococcal vaccination in the primary prevention of heart attacks and strokes. People aged 55 to 60 from 6 sites around Australia will be invited to participate in the study. The selected participants will attend a
clinic in their area and will be randomly given the pneumococcal vaccine or a placebo vaccine. Outcomes on the expected 6000 participants will
be ascertained by health record linkage with government databases after 6 years.
Trial website
https://AUSPICE.apps.hmri.com.au
Trial related presentations / publications
Public notes
There are multiple post-codes for recruitment. Each site will have postcodes within 25km radius of the main city postcode.

The participants are otherwise healthy in that they do not have any immunological or chronic diseases or the outcome of cardiovascular diseases. The aim of the study is to see if the pneumococcal vaccine can prevent CVD in those at risk of CVD.

Contacts
Principal investigator
Name 57082 0
Prof John Attia
Address 57082 0
Level 4 West Hunter Medical Research Institute 1 Kookaburra Ct New Lambton Heights NSW 2305
Country 57082 0
Australia
Phone 57082 0
+61240420515
Fax 57082 0
+61 2 4042 0044
Email 57082 0
[email protected]
Contact person for public queries
Name 57083 0
Ms Roseanne Peel
Address 57083 0
Level 4 West
Hunter Medical Research Institute
1 Kookaburra Cl
New Lambton Heights
NSW 2305
Country 57083 0
Australia
Phone 57083 0
+61240420523
Fax 57083 0
+61 2 4042 0044
Email 57083 0
[email protected]
Contact person for scientific queries
Name 57084 0
Prof John Attia
Address 57084 0
Level 4 West Hunrer Medical Research Institute 1 Kookaburra Ct New Lambton Heights NSW 2305
Country 57084 0
Australia
Phone 57084 0
+61240420515
Fax 57084 0
+61 2 4042 0044
Email 57084 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7093Ethical approval    368506-(Uploaded-20-02-2020-10-15-25)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes accepted April 12, 2016 http://dx.doi.org/10.1016... [More Details]
Study results articleYes accepted 24 January 2019 https://doi.org/10.5694/... [More Details]
Study results articleYes J Med Internet Res 2019 | vol. 21 | iss. 10 | e147... [More Details]
Study results articleYes Received 19 September 2021; Received in revised fo... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRationale and design of a randomized controlled trial of pneumococcal polysaccharide vaccine for prevention of cardiovascular events: The Australian Study for the Prevention through Immunization of Cardiovascular Events (AUSPICE).2016https://dx.doi.org/10.1016/j.ahj.2016.04.003
EmbaseParticipant-Centered Online Active Surveillance for Adverse Events Following Vaccination in a Large Clinical Trial: Feasibility and Usability Study.2019https://dx.doi.org/10.2196/14791
EmbaseImmunomodulation Therapies for Atherosclerosis: The Past, the Present, and the Future.2023https://dx.doi.org/10.3390/ijms241310979
EmbasePersistence of Detectable Anti-Pneumococcal Antibodies 4 Years After Pneumococcal Polysaccharide Vaccination in a Randomised Controlled Trial: The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE).2023https://dx.doi.org/10.1016/j.hlc.2023.09.006
EmbaseOpportunities for an atherosclerosis vaccine: From mice to humans.2020https://dx.doi.org/10.1016/j.vaccine.2019.12.039
N.B. These documents automatically identified may not have been verified by the study sponsor.