Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000771954
Ethics application status
Approved
Date submitted
20/05/2020
Date registered
27/07/2020
Date last updated
4/08/2023
Date data sharing statement initially provided
27/07/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
PREDICTive value of aggressive risk factor modification on the development of atrial fibrillation in Embolic Stroke of Undetermined Source. Staging the Atrial Fibrillation Substrate: The PREDICT-ESUS study
Scientific title
PREDICTive value of aggressive risk factor modification on the development of atrial fibrillation in Embolic Stroke of Undetermined Source. Staging the Atrial Fibrillation Substrate: The PREDICT-ESUS study
Secondary ID [1] 300817 0
Nil
Universal Trial Number (UTN)
Trial acronym
PREDICT-ESUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 316705 0
Stroke 316706 0
Condition category
Condition code
Cardiovascular 314949 314949 0 0
Other cardiovascular diseases
Stroke 315855 315855 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study intervention to be evaluated is aggressive risk factor modification. Risk factors including obesity, hypertension, dyslipidaemia, glucose intolerance/diabetes, obstructive sleep apnoea, physical activity levels, alcohol, and tobacco use will be sought and evaluated in each participant. Each of the relevant risk factors for that given individual is then targeted aggressively.

Risk factor modification will be performed in a physician-led clinic with appointments and contact frequency adjusted according to individual needs. These range from 3-monthly formal appointments to weekly contact by phone or email.

Participants will receive regular consultation from a doctor or nurse, with or without exercise physiologist input regarding risk factor modification via any appropriate intensification of treatment for hypertension, dyslipidaemia, diabetes/glucose intolerance, obstructive sleep apnoea, weight loss, regular exercise, smoking cessation and reduction in alcohol consumption. Intensification of treatment will include medication increase as required, adjustment of meal plans and modified exercise programs. Face-to-face interview and/or telephone/video calls will involve an initial assessment and follow-up appointments of 30-60 minutes. Anticoagulation according to standard indications for any atrial fibrillation detected will be prescribed utilising the appropriate oral anticoagulation agent. A structured, motivational, and goal-directed program will be used for weight reduction within scheduled sessions, with encouragement to keep an accurate food and physical activity diary. Measurements of weight, blood pressure and results from any appropriate re-assessment of tests such as serum cholesterol or glucose will be evaluated at each visit. Participants will be encouraged to utilise support counselling and schedule more frequent reviews as required. In participants with a body mass index (BMI) greater than or equal to 27kg/m2, a meal plan and behaviour modification will be utilised initially for weight reduction. The initial goal is to reduce body weight by 10%. An accredited exercise physiologist will prescribe regular exercise with a target of 180 minutes per week of moderate aerobic exercise and 30 minutes of home-based resistance training. The exercise prescription will be initiated according to baseline exercise testing and physical activity profile. Participants will be encouraged to increase their exercise habits progressively until they reach the weekly target volume. Adherence to treatment strategies will be assessed at each visit via comparison of prescribed diet, exercise and medication changes with exercise and food diary.
Intervention code [1] 317596 0
Treatment: Other
Intervention code [2] 317597 0
Behaviour
Intervention code [3] 317598 0
Lifestyle
Comparator / control treatment
Standard of care: Participants in the control group will receive standard medical therapy for stroke as per current national and international guidelines.
Control group
Active

Outcomes
Primary outcome [1] 323799 0
AF incidence (greater than or equal to 2 minutes in duration) recorded on Implantable Cardiac Monitor.
Timepoint [1] 323799 0
36 months
Secondary outcome [1] 382924 0
Clinical and radiological recurrence of stroke assessed using cranial imaging
Timepoint [1] 382924 0
36 months
Secondary outcome [2] 382925 0
Change in left atrial size on transthoracic echocardiography
Timepoint [2] 382925 0
36 months
Secondary outcome [3] 382926 0
Change in inflammatory markers including hsCRP, IL-6, TNF-alpha using serum assay
Timepoint [3] 382926 0
36 months
Secondary outcome [4] 383662 0
Change in left atrial function on speckle tracking echocardiography
Timepoint [4] 383662 0
36 months
Secondary outcome [5] 383663 0
Change in left atrial electrical characteristics on ECGi
Timepoint [5] 383663 0
36 months
Secondary outcome [6] 383664 0
Change in coagulopathy markers including Thrombin-antithrombin complex, P-selectin (CD62P) and collagen using serum assay
Timepoint [6] 383664 0
36 months
Secondary outcome [7] 383665 0
Change in leukocyte telomere length using serum assay
Timepoint [7] 383665 0
36 months

Eligibility
Key inclusion criteria
o Primary diagnosis of ESUS
o No history of documented atrial fibrillation or flutter during 24 hours of ward telemetry or ambulatory Holter monitoring
o No known history of AF or flutter
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
o Documented atrial fibrillation or flutter prior to randomisation
o Serious Underlying Medical Disorder
o Age < 18
o Inability to Provide Informed Consent
o Being fully anticoagulated prior to randomisation
o Moderate-Severe Valvular Heart disease
o Prosthetic Heart Valve
o Endocrinopathy including subclinical thyroid disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised using a computer-generated web-based randomisation schedule. Randomisation will be stratified by trial centre using randomly permuted blocks of sizes 2 and 4.
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
Not applicable
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical methods/analysis:The study will be 80% powered with an alpha value of 0.05 to assess for reduction in radiologic recurrence of stroke and reduction of atrial fibrillation in the intervention group. Stroke recurrence: with a sample size of 270 participants (135 in each group) and a planned follow-up at 36-months, 50% reduction in radiological recurrence of stroke is expected. AF burden: with a sample size of 400 participants (200 in each group), and a planned follow-up of 36-months, 50% reduction in AF burden is expected in the intervention group. Thus the overall study sample size will be 400 participants, with 200 in each group and each participant will be assessed for both outcomes individually.

Data Analysis: All continuous variables will be reported as mean with standard deviation (SD). Participant characteristics, including cardiovascular risk factors and echocardiography parameters, will be compared at follow-up by analysis of covariance (ANCOVA) with adjustment for baseline values. The primary endpoints (AF incidence and Stroke recurrence) will each be compared between groups using Cox regression for survival analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/08/2020
Actual
17/02/2021
Date of last participant enrolment
Anticipated
10/01/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
400
Accrual to date
63
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 16676 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 16678 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 16679 0
Calvary Wakefield Hospital - Adelaide
Recruitment hospital [4] 16681 0
Ashford Community Hospital - Ashford
Recruitment postcode(s) [1] 30272 0
5000 - Adelaide
Recruitment postcode(s) [2] 30274 0
5011 - Woodville
Recruitment postcode(s) [3] 30276 0
5035 - Ashford

Funding & Sponsors
Funding source category [1] 305274 0
University
Name [1] 305274 0
Centre for Heart Rhythm Disorders, University of Adelaide
Country [1] 305274 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
North Terrace, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 306159 0
None
Name [1] 306159 0
Address [1] 306159 0
Country [1] 306159 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305617 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 305617 0
Royal Adelaide Hospital
Port Road, Adelaide SA 5000
Ethics committee country [1] 305617 0
Australia
Date submitted for ethics approval [1] 305617 0
Approval date [1] 305617 0
27/01/2019
Ethics approval number [1] 305617 0
R20190107

Summary
Brief summary
Among strokes resulting from blood vessel blockage leading to sudden damage to the brain (known as ischaemic strokes), just under one third have no underlying cause found despite extensive investigations and most of these are known as embolic stroke of undetermined source (ESUS). To prevent recurrence of these strokes, we hypothesise that intervention to modify risk factors (including being overweight, smoking, diabetes, high blood pressure, high cholesterol, alcohol use, and sleep apnoea) could lead to reduced recurrent strokes and reduced onset of atrial fibrillation (an irregular heart rhythm also known to lead to stroke) in stroke survivors. This risk factor modification, delivered via visits to a specialised risk factor modification clinic, already proven to improve outcomes in atrial fibrillation, will be compared in this study with usual post-stroke medical care. If validated in a separate group of participants without stroke, a special surface ECG’ mapping’ vest will be applied to assess and re-assess the upper heart chamber health of participants with stroke at the beginning and end of this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100974 0
Prof Prash Sanders
Address 100974 0
Centre for Heart Rhythm Disorders
University of Adelaide
North Terrace, Adelaide SA 5000
Country 100974 0
Australia
Phone 100974 0
+61 08 8313 9000
Fax 100974 0
Email 100974 0
[email protected]
Contact person for public queries
Name 100975 0
Dr John Fitzgerald
Address 100975 0
Centre for Heart Rhythm Disorders
University of Adelaide
North Terrace, Adelaide SA 5000
Country 100975 0
Australia
Phone 100975 0
+61 08 8313 9000
Fax 100975 0
Email 100975 0
[email protected]
Contact person for scientific queries
Name 100976 0
Prof Prash Sanders
Address 100976 0
Centre for Heart Rhythm Disorders
University of Adelaide
North Terrace, Adelaide SA 5000
Country 100976 0
Australia
Phone 100976 0
+61 08 8313 9000
Fax 100976 0
Email 100976 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?

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.