COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

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
ACTRN12620000704998p
Ethics application status
Submitted, not yet approved
Date submitted
20/05/2020
Date registered
29/06/2020
Date last updated
29/06/2020
Date data sharing statement initially provided
29/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
PREDICTive value of aggressive risk factor modification on the occurrence of major cardiovascular events in patients with embolic STROKE: PREDICT-STROKE
Scientific title
PREDICTive value of aggressive risk factor modification on the occurrence of major cardiovascular events in patients with embolic STROKE: PREDICT-STROKE
Secondary ID [1] 300806 0
Nil
Universal Trial Number (UTN)
Trial acronym
PREDICT-STROKE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 316687 0
Stroke 318023 0
Condition category
Condition code
Cardiovascular 314933 314933 0 0
Other cardiovascular diseases
Stroke 315863 315863 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. At each appointment, medications, blood pressure and any serum lipids taken will be reviewed. Medications will be increased where required, meal plans and exercise regimes will be modified accordingly. 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] 317135 0
Lifestyle
Intervention code [2] 317136 0
Treatment: Other
Intervention code [3] 317137 0
Behaviour
Comparator / control treatment
Participants who are randomised to the control arm will receive standard medical therapy. Standard medical therapy for stroke as per current national and international guidelines include antiplatelet therapy (aspirin 50 to 325mg/day alone, or aspirin combined with clopidogrel monotherapy), statin therapy and treatment of co-morbidities. These participants will also be issued with once off written and verbal advice regarding health nutrition and exercise guidelines at commencement of their participation and weight management is a self-directed process. Completion of a diet and activity diary will not be requested. Risk
factor treatment in this group will be at the discretion of the referring physicians.
Control group
Active

Outcomes
Primary outcome [1] 323244 0
A composite of major adverse cardiovascular events defined as stroke, systemic embolism, asymptomatic cerebral embolism, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularisation, or death from cardiovascular cause, assessed by participant medical records and self report assessment.
Timepoint [1] 323244 0
12 months
Secondary outcome [1] 381281 0
Change in quality of life assessed by the SF-36 questionnaire.
Timepoint [1] 381281 0
6, 12 months
Secondary outcome [2] 381282 0
All-cause mortality assessed through medical records cross-referenced with family contact. Death certificate retrieval
Timepoint [2] 381282 0
12 months
Secondary outcome [3] 381283 0
Cardiovascular mortality assessed through medical records cross-referenced with family contact. Death certificate retrieval
Timepoint [3] 381283 0
12 months
Secondary outcome [4] 381285 0
Asymptomatic cerebral embolism as assessed by MRI brain
Timepoint [4] 381285 0
12 months
Secondary outcome [5] 381286 0
Atrial fibrillation burden assessed by implantable loop recorder where implanted (after ESUS), or holter monitoring and surface ECG where no loop recorder is implanted
Timepoint [5] 381286 0
12 months
Secondary outcome [6] 381287 0
Clinical stroke recurrence assessed via medical history obtained from participants and hospitalisation history for stroke
Timepoint [6] 381287 0
12 months
Secondary outcome [7] 381435 0
Radiological recurrence of stroke determined by a repeat magnetic resonance imaging (MRI).
Timepoint [7] 381435 0
12 months

Eligibility
Key inclusion criteria
• At least 18 years old
• Embolic Stroke or TIA
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• < 18 years
• Pregnancy or planned pregnancy within the next 24 months
• Non-English Speaking
• Major Surgery <6 months
• Valvular Disease Needing Intervention
• LVEF equal to or less than 35%
• Active Malignancy
• Autoimmune or Systemic Inflammation
• Severe Renal or Liver Dysfunction
• Malabsorption Disorders
• Pregnancy
• Institutional Living
• Inability to Attend Appointments
• Inability to Provide Informed Consent

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
Sample size calculation for this trial is based on the composite primary endpoint of major adverse cardiovascular events (MACE). The following assumptions were considered: (1) 12-month minimum follow-up; (2) 48 % annual risk of composite endpoint (33% for recurrent stroke, any acute coronary syndrome, vascular death, combined with 15% for asymptomatic cerebral embolism); (3) 25% reduction in MACE recurrence with our planned intervention compared to the standard care group; (4) 15% attrition rate (loss-to-follow-up or withdrawal of consent); (5) 1:1 allocation ratio.

The study will require 530 participants (265 in each arm) with a = 0.05 and an 80% power. Considering the 15% attrition rate, the recruitment aim is for a total of 624 participants (312 in each arm). Statistical analysis will be performed by a senior statistician with experience in managing clinical trial data. Analyses will be conducted under the intention to treat principle. Logistic regression will be used to calculate hazard ratios for the composite primary end point. Time to event data will be analysed using the Kaplan-Meier method with comparison between-groups using Log-Rank statistics with two degrees of freedom. Pre-specified subgroup analysis will be performed using Cox-proportional hazards regression specifically for participants with a diagnosis of ESUS.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,SA,VIC
Recruitment hospital [1] 16132 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 16133 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 16134 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 16135 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [5] 16136 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [6] 16138 0
The Canberra Hospital - Garran
Recruitment postcode(s) [1] 29666 0
2605 - Garran
Recruitment postcode(s) [2] 29663 0
3052 - Parkville
Recruitment postcode(s) [3] 29664 0
3084 - Heidelberg
Recruitment postcode(s) [4] 29660 0
5000 - Adelaide
Recruitment postcode(s) [5] 29661 0
5011 - Woodville
Recruitment postcode(s) [6] 29662 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 305262 0
University
Name [1] 305262 0
University of Adelaide
Address [1] 305262 0
North Terrace, Adelaide SA 5000
Country [1] 305262 0
Australia
Primary sponsor type
University
Name
Centre for Heart Rhythm Disorders, University of Adelaide
Address
North Terrace, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 305623 0
None
Name [1] 305623 0
Address [1] 305623 0
Country [1] 305623 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305605 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 305605 0
Royal Adelaide Hospital
Port Road, Adelaide SA 5000
Ethics committee country [1] 305605 0
Australia
Date submitted for ethics approval [1] 305605 0
11/05/2020
Approval date [1] 305605 0
Ethics approval number [1] 305605 0

Summary
Brief summary
Stroke is a leading cause of cardiovascular-related morbidity and mortality in Australia, with approximately one third of strokes being cryptogenic, meaning that they are of undetermined cause. The majority of these are due to embolic stroke of undetermined source (ESUS). Unfortunately, little is known about the underlying causes of ESUS and effective strategies for primary and secondary prevention of recurrent stroke in this population. The purpose of this trial is to determine whether aggressive risk factor modification compared to usual care in patients with embolic stroke can significantly reduce the occurrence of major cardiovascular events. Risk factors including, obesity, hypertension, dyslipidemia, glucose intolerance or diabetes, obstructive sleep apnoea, physical inactivity, alcohol excess and tobacco use will be systematically targeted.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100934 0
Prof Prashanthan Sanders
Address 100934 0
Centre for Heart Rhythm Disorders
University of Adelaide/Royal Adelaide Hospital
Port Road, Adelaide, SA, 5000
Country 100934 0
Australia
Phone 100934 0
+61 08 8313 9000
Fax 100934 0
Email 100934 0
prash.sanders@adelaide.edu.au
Contact person for public queries
Name 100935 0
Dr John Fitzgerald
Address 100935 0
Centre for Heart Rhythm Disorders
University of Adelaide/Royal Adelaide Hospital
Port Road, Adelaide, SA, 5000
Country 100935 0
Australia
Phone 100935 0
+61 08 8313 9000
Fax 100935 0
Email 100935 0
john.fitzgerald@adelaide.edu.au
Contact person for scientific queries
Name 100936 0
Dr John Fitzgerald
Address 100936 0
Centre for Heart Rhythm Disorders
University of Adelaide/Royal Adelaide Hospital
Port Road, Adelaide, SA, 5000
Country 100936 0
Australia
Phone 100936 0
+61 08 8313 9000
Fax 100936 0
Email 100936 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 other documents available
Summary results
No Results