Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000411640
Ethics application status
Approved
Date submitted
5/04/2023
Date registered
26/04/2023
Date last updated
26/04/2023
Date data sharing statement initially provided
26/04/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Left Atrial Structure and Function in Embolic Stroke of Undetermined Source compared with Atrial Fibrillation (ES-AF)
Scientific title
Left Atrial Structure and Function in Embolic Stroke of Undetermined Source compared with Atrial Fibrillation (ES-AF)
Secondary ID [1] 309175 0
Nil
Universal Trial Number (UTN)
Trial acronym
ES-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 329389 0
Atrial Fibrillation 329390 0
Condition category
Condition code
Stroke 326335 326335 0 0
Ischaemic
Cardiovascular 326336 326336 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Observational

This study will evaluate left atrial structure and function in participants who have experienced embolic stroke of undetermined source, compared with participants who have a history of atrial fibrillation, and a group who have no history of either of these conditions. Participants will have a one-off measurement of parameters within 12 months of embolic stroke or atrial fibrillation diagnosis. Measurements will be performed during recruitment between July 2020 and July 2023.

Left atrial function will be evaluated through resting and exercise echocardiographic imaging of left atrial emptying fraction, dimensions and strain parameters.

Exercise capacity will be evaluated through cardiopulmonary exercise testing utilising a standardised bicycle protocol and metabolic cart.

Left atrial and cardiac structure will be evaluated through CT imaging of left atrium, pulmonary veins and epicardial adipose tissue.
Intervention code [1] 325676 0
Diagnosis / Prognosis
Comparator / control treatment
An age-matched group with no history of AF or ESUS will be selected and testing performed.
Control group
Active

Outcomes
Primary outcome [1] 334188 0
Left Atrial Emptying Fraction during exercise measured on 2D echocardiography
Timepoint [1] 334188 0
Single measurement within 12 months of stroke or at any time-point after atrial fibrillation diagnosis
Secondary outcome [1] 419776 0
left Atrial Strain during exercise measured on 2D echocardiography
Timepoint [1] 419776 0
Single measurement within 12 months of stroke or at any time-point after atrial fibrillation diagnosis
Secondary outcome [2] 419777 0
Left Ventricular Strain during exercise measured on 2D echocardiography
Timepoint [2] 419777 0
Single measurement within 12 months of stroke or at any time-point after atrial fibrillation diagnosis
Secondary outcome [3] 419778 0
VO2 Max on Cardiopulmonary Exercise Testing using a metabolic cart
Timepoint [3] 419778 0
Single measurement within 12 months of stroke or at any time-point after atrial fibrillation diagnosis
Secondary outcome [4] 419779 0
Serum N-terminal Pro-Brain Natriuretic Peptide level
Timepoint [4] 419779 0
Single measurement within 12 months of stroke or at any time-point after atrial fibrillation diagnosis
Secondary outcome [5] 420383 0
Epicardial Fat volume as measured on Cardiac Computed Tomography
Timepoint [5] 420383 0
Single measurement within 12 months of stroke or at any time-point after atrial fibrillation diagnosis

Eligibility
Key inclusion criteria
At least 18 years old
Embolic Stroke of Undetermined Source (ESUS) subgroup - history of ESUS
Atrial Fibrillation (AF) subgroup - history of AF
Comparison group - no history of either of these conditions (AF or ESUS)
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Age > 85 years
• Pregnancy or planned pregnancy within the next 24 months
• Unable to undergo MRI scan
• Major Surgery <6 months
• Valvular Disease Needing Intervention
• LVEF equal to or less than 35%
• Active Malignancy
• Autoimmune or Systemic Inflammation
• Specific Stroke Mechanisms: Patent Foramen Ovale, Vessel Dissection, Subacute Bacterial Endocarditis • Severe Renal Dysfunction (defined as dialysis, prior or planned transplant, Cr >2.26 mg/dl or > 200 µmol/L)
• Severe Liver Dysfunction (Cirrhosis or Bilirubin > 2 x Normal or AST/ALT/ALP > 3x Normal)
• Malabsorption Disorders
• Institutional Living
• Inability to Attend Appointments
• Inability to Provide Informed Consent

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Assuming a normal Exercise Left Atrial Emptying Fraction (LA EF) as shown in previous studies of 67 +/-10%, to determine 10% difference in LA EF during exercise between embolic stroke of undetermined source and control groups, 27 participants per group gives 90% power with alpha 0.025. Target recruitment is 30 participants in each group to allow for 10% inadequate imaging acquisition in each group. Comparison will be made with exercise LAEF in an additional 30 participants with known Atrial fibrillation.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/06/2020
Date of last participant enrolment
Anticipated
30/09/2023
Actual
Date of last data collection
Anticipated
30/09/2023
Actual
Sample size
Target
90
Accrual to date
50
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 39855 0
5000 - Adelaide
Recruitment postcode(s) [2] 39856 0
5067 - Norwood

Funding & Sponsors
Funding source category [1] 313373 0
University
Name [1] 313373 0
University of Adelaide
Country [1] 313373 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
North Terrace, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 315189 0
None
Name [1] 315189 0
Address [1] 315189 0
Country [1] 315189 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312590 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 312590 0
Royal Adelaide Hospital
Port Road, Adelaide SA 5000
Ethics committee country [1] 312590 0
Australia
Date submitted for ethics approval [1] 312590 0
01/06/2020
Approval date [1] 312590 0
01/06/2020
Ethics approval number [1] 312590 0
13232 and 11901

Summary
Brief summary
Function of the cardiac left atrial chamber is known to be impaired in people with atrial fibrillation, a condition principally related to this structure. In people who have an ischaemic stroke, roughly one quarter will have no definite cause found despite extensive imaging and other tests, though up to 30 percent of these will have atrial fibrillation diagnosed on implantable cardiac monitoring in the 3 years after stroke. The purpose of this study is to determine if a proportion of this group with stroke of undetermined source have signs of left atrial cardiomyopathy, evidenced by low left atrial reserve at rest and during exertion seen on echocardiographic imaging, and if this is reflected by impaired exercise tolerance, altered blood test biomarkers, or left atrial structure and epicardial fat abnormalities on computed tomography.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125206 0
Prof Prashanthan Sanders
Address 125206 0
Centre for Heart Rhythm Disorders
University of Adelaide/Royal Adelaide Hospital Port Road, Adelaide, SA, 5000
Country 125206 0
Australia
Phone 125206 0
+61 08 8313 9000
Fax 125206 0
Email 125206 0
prash.sanders@adelaide.edu.au
Contact person for public queries
Name 125207 0
Dr John Fitzgerald
Address 125207 0
Centre for Heart Rhythm Disorders
University of Adelaide/Royal Adelaide Hospital Port Road, Adelaide, SA, 5000
Country 125207 0
Australia
Phone 125207 0
+61 08 8313 9000
Fax 125207 0
Email 125207 0
john.fitzgerald@adelaide.edu.au
Contact person for scientific queries
Name 125208 0
Dr John Fitzgerald
Address 125208 0
Centre for Heart Rhythm Disorders
University of Adelaide/Royal Adelaide Hospital Port Road, Adelaide, SA, 5000
Country 125208 0
Australia
Phone 125208 0
+61 08 8313 9000
Fax 125208 0
Email 125208 0
john.fitzgerald@adelaide.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


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.