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Trial registered on ANZCTR


Registration number
ACTRN12621001460897
Ethics application status
Approved
Date submitted
27/08/2021
Date registered
26/10/2021
Date last updated
21/04/2022
Date data sharing statement initially provided
26/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of screening for Atrial Fibrillation with ECG on the incidence of stroke - a randomised controlled trial
Scientific title
Randomised controlled trial to determine if screening for atrial fibrillation (AF) in primary care of adults aged over 70 is effective and cost effective in reducing stroke and other key outcomes (both harm and benefit) compared to current practice.
Secondary ID [1] 304760 0
ISRCTN16939438
Universal Trial Number (UTN)
Trial acronym
SAFER-AUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation
 322805 0
Stroke 322806 0
Condition category
Condition code
Stroke 320395 320395 0 0
Ischaemic
Stroke 321206 321206 0 0
Haemorrhagic
Cardiovascular 321509 321509 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Atrial Fibrillation (AF) Screening will be conducted using a single-lead Zenicor handheld ECG device, which has TGA approval. A 30-second lead-1 ECG is recorded by holding thumbs on the electrodes. ECG traces are not displayed or analysed on the recorder, and are transmitted over a cellular network to the central Zenicor database by pushing the send button. The Zenicor algorithm classifies each ECG trace as ‘possible AF’, ‘no tag’, ‘other deviations’ or ‘poor quality. The Zenicor has 98% sensitivity and 92% specificity, which is ideal for this style of screening due to the low false negative rate.

Consented participants will be contacted by the research staff by telephone to alert them package dispatch (~5mins) and a Zenicor ECG device (with user manual) will then be sent to the participant’s home. Research staff will be available for a further phone call or video conference if required to help the participant use the Zenicor ECG. The participant will be requested to record 4 ECGs a day for 3 weeks, plus additional recordings if AF symptoms are experienced. The number of additional recordings will be determined by a cardiologist at the time of review.
All recorded ECGs are logged within the Zenicor system for coordinators to track adherence to the outlined uses of the device.
Intervention code [1] 321138 0
Early detection / Screening
Comparator / control treatment
Standard of care (no screening device). participants will be monitored and treated for symptoms of AF as per the national Australian heart guidelines.
Control group
Active

Outcomes
Primary outcome [1] 328231 0
Incidence of stroke (both ischaemic and haemorrhagic) as assessed by data linkage to patient medical record
Timepoint [1] 328231 0
Five years following study commencement.
Secondary outcome [1] 398215 0
Incidence of myocardial infarction as assessed by data linkage to patient medical record
Timepoint [1] 398215 0
Five years following study commencement.
Secondary outcome [2] 398216 0
Incidence of bleeding episodes requiring hospital admission as assessed by data linkage to patient medical record
Timepoint [2] 398216 0
Five years following study commencement.
Secondary outcome [3] 398218 0
Proportion of confirmed AF detected through screening, or newly detected AF patients, who were started on anticoagulation according to guideline recommendations.
This will be assessed as a composite outcome
Timepoint [3] 398218 0
Five years following study commencement.
Secondary outcome [4] 398220 0
`To assess the process of Australian implementation of the screening protocol, and understand the patient and practice perspectives on screening via process evaluation and qualitative studies.
This will be assessed as a composite outcome.
Timepoint [4] 398220 0
Five years following study commencement.
Secondary outcome [5] 398221 0
Cost-effectiveness analysis in the Australian setting (future planned analysis based on 5-year trial outcomes) to be assessed using health data, costs and demographics & EQ-5D
Timepoint [5] 398221 0
Five years following study commencement.
Secondary outcome [6] 401066 0
Incidence of heart failure as assessed by data linkage to patient medical record
Timepoint [6] 401066 0
Five years following study commencement.
Secondary outcome [7] 401067 0
Incidence of all cardiovascular events as assessed by data linkage to patient medical record
Timepoint [7] 401067 0
Five years following study commencement.
Secondary outcome [8] 401068 0
Incidence of fatal cardiovascular events as assessed by data linkage to patient medical record
Timepoint [8] 401068 0
Five years following study commencement.
Secondary outcome [9] 401069 0
Incidence of death as assessed by data linkage to patient medical record
Timepoint [9] 401069 0
Five years following study commencement.
Secondary outcome [10] 401070 0
Incidence of dementia as assessed by data linkage to patient medical record
Timepoint [10] 401070 0
Five years following study commencement.

Eligibility
Key inclusion criteria
a) Age greater than or equal to 70 years, with no upper age limit (as recorded on the practice medical record).
b) Either: No diagnosis of AF; OR AF diagnosis but not on anticoagulation.
c) Have provided informed consent to participate.
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Long-term anticoagulation therapy for stroke prevention.
b) Receiving palliative care or known to be residing in a Nursing home.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation. Randomisation of participants will take place after the recruitment window has closed. Randomisation will be stratified by GP practice. Participants will be individually randomised at a ratio of 2:1 to control or intervention (AF screening).
Participants remain blinded at the consent stage to whether they will receive screening or not.
Where there is more than one participant in the same household, these participants will be randomised as a cluster (i.e., receive the same allocation) to avoid contamination.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
For 90% power to detect a clinically meaningful 10% relative reduction in five-year stroke risk in the trial population (from 4.17% to 3.73%) SAFER will need to recruit 31,000 individually randomised participants in intervention arm and 62,000 participants in the control arm, assuming an average follow-up of 5 years. To account for clusters of households, it is estimated that at least 24% of practice patients to be from the same household. Assuming each household cluster is of size 2, we expect 3722 clusters of size 2 and 23572 clusters of size 1 in the intervention arm with an overall expected cluster size of 1.14. An estimate of the intraclass correlation coefficient at the household level for doctor diagnosed stroke is 0.20573. With the variable cluster sizes outlined above this gives a design effect of 1.043. This sample size will provide 90% power at 5% significance level to detect a 1.1% absolute difference in the rate of diagnosis of new AF participants between intervention and control, assuming 3% newly diagnosed AF are detected in screened patients and an intra-class correlation coefficient of 0.001. The sample size calculation makes the following assumptions derived from the UK pilot study: a) 40% agree to participation from initial invite; b) from 350 consented patients per intervention practice, only 300 (85%) will be screened; c) 3% of screened patients will be detected with newly diagnosed AF; d) 80% of newly diagnosed AF patients will commence anticoagulation; and e) 55% of patients with known AF reviewed as a result of the screening will commence anticoagulation.

In addition to the 97,024 participants recruited in the UK, SAFER-AUS will recruit 780 participants across 3 states. Hence, SAFER-AUS will provide approximately 8% of the total information with an additional 10% of practices because of intra-class correlation.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2022
Actual
Date of last participant enrolment
Anticipated
18/07/2022
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
2340
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS,WA
Recruitment outside Australia
Country [1] 23956 0
United Kingdom
State/province [1] 23956 0

Funding & Sponsors
Funding source category [1] 309130 0
Government body
Name [1] 309130 0
Australian Government Department of Health
Country [1] 309130 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trials Centre
Medical Foundation Building (K25)
The University of Sydney
Level 6, 92-94 Parramatta Rd
CAMPERDOWN NSW 2050
Country
Australia
Secondary sponsor category [1] 310084 0
None
Name [1] 310084 0
Address [1] 310084 0
Country [1] 310084 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308997 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 308997 0
Ethics committee country [1] 308997 0
Australia
Date submitted for ethics approval [1] 308997 0
27/07/2021
Approval date [1] 308997 0
21/12/2021
Ethics approval number [1] 308997 0

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

Contacts
Principal investigator
Name 112598 0
Prof Ben Freedman
Address 112598 0
Room 3114, 3E Charles Perkins Centre, D17,
University of Sydney,
Johns Hopkins Dr, Camperdown NSW 2006
Country 112598 0
Australia
Phone 112598 0
+61 2 9114 2199
Fax 112598 0
Email 112598 0
ben.freedman@sydney.edu.au
Contact person for public queries
Name 112599 0
Rebecca Mister
Address 112599 0
NHMRC Clinical Trials Centre
Level 6, Medical Foundation Building (K25)
92-94 Parramatta Rd
CAMPERDOWN NSW 2050
Country 112599 0
Australia
Phone 112599 0
+61 2 9562 5000
Fax 112599 0
Email 112599 0
safer-aus.study@sydney.edu.au
Contact person for scientific queries
Name 112600 0
Rebecca Mister
Address 112600 0
NHMRC Clinical Trials Centre
Level 6, Medical Foundation Building (K25)
92-94 Parramatta Rd
CAMPERDOWN NSW 2050
Country 112600 0
Australia
Phone 112600 0
+61 2 9562 5000
Fax 112600 0
Email 112600 0
safer-aus.study@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be shared. A summary of the study data will be published in a peer reviewed journal.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.