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Trial registered on ANZCTR


Registration number
ACTRN12625000104459
Ethics application status
Approved
Date submitted
29/10/2024
Date registered
30/01/2025
Date last updated
30/01/2025
Date data sharing statement initially provided
30/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Atrial Myopathy and Embolic Stroke (AMES) trial – Prospective Randomised Open Blinded Endpoint (PROBE) clinical trial with parallel cohort study
Scientific title

Effect of anticoagulant on Recurrence After Cryptogenic Stroke in Patients With Atrial Myopathy: The AMES randomized clinical trial with parallel cohort study.
Secondary ID [1] 313263 0
none
Universal Trial Number (UTN)
Trial acronym
AMES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with Acute ischemic stroke 335589 0
impaired left atrial (LA) function 335590 0
Condition category
Condition code
Cardiovascular 332160 332160 0 0
Other cardiovascular diseases
Stroke 332387 332387 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with ischemic stroke deemed to be embolic with no clearly identified aetiology after standard evaluation (Embolic Stroke of Uncertain Source, ESUS) will be enrolled. Patients will undergo transthoracic echocardiography and be divided into two groups: impaired left atrial (LA) function (reduced 'strain', indicating atrial myopathy) and normal left atrial function. This study includes an RCT and a simultaneous prospective cohort study. The RCT will be a multi-centre ,parallel group, prospective, randomised open, blinded endpoint trial. The arms are as follow:
1. Patients with impaired left atrial function will be randomised to the intervention of Direct Acting Oral Anticoagulant (DOAC) vs. standard (guideline based) antiplatelet care (1:1 allocation ratio).
2. Patients without atrial myopathy (i.e. with normal left atrial function and thus ineligible for the RCT), will be allocated to standard care
3.Patients without atrial myopathy and as well as the patients with atrial myopathy in the RCT, who were ,randomised to standard care, will form the two parallel arms of the longitudinal cohort study.
Follow-up :
All participant, either , in RCT or cohort study, will have the same follow-up and observations at Baseline, at 6 months after enrolment, and at 24 months after enrolment.

RCT component: Direct Acting Oral Anticoagulant (DOAC) VS standard care.
Cohort Study component : Normal LA strain and Normal LA Volume participants allocated to standard care.

Direct Acting Oral Anticoagulant (DOAC) VS standard care.
Participants who will be randomised , to be administered one of the three DOACs as per the neurologists choice of the DOAC. Tablet will be taken orally.
Rivaroxaban , apixaban and Dabigatran are administered at a fixed dose without monitoring.
• Rivaroxaban: 20 mg once daily with the evening meal for 24 months following enrolment (creatinine clearance [CrCl] greater than 50 mL/minute); or 15 mg once daily with the evening meal for 24 months following enrolment (CrCl equal to 50 mL/minute).
• Apixaban: 5 mg twice daily for 24 months following enrolment (CrCl greater than 50 mL/minute); or 2.5 mg twice daily ,for 24 months following enrolment ,for those with any two of the following: age is greater than or equal to 80 years, body weight is less than or equal to 60 kg, or serum creatinine is equal to 1.5 mg/dL.
• Dabigatran :110 mg orally twice daily or 150 mg orally twice daily, for 24 months following enrolment (CrCl greater than 30 mL/minute). Dabigatran is generally given at a fixed dose without monitoring.

Intervention Adherence will be done in the following ways :
Patient Self-Report: Asking the participant directly about their medication-taking habits.
Pill Counts: Have patients return unused medication, allowing site to calculate how many doses they have taken compared to what was prescribed.
Pharmacy Refill Records: Review prescription refill history to see if the patient is picking up their medication as prescribed.
Clinical Assessments: Monitor the participant’s clinical progress. Improvement in symptoms can indicate adherence, although it’s not definitive.
Support Systems: Implement reminders or support groups (family) to encourage adherence and check in with patients regularly.

COHORT STUDY PARTICIPANTS:
The follow-up and observations will be exactly the same as RCT participants, at Baseline, at 6 months after enrolment, and at 24 months after enrolment.
The following assessments will be attained for Cohort patients (these assessments have been widely described ) :

• Baseline: Physical examination, NIHSS, MoCA, estimate of pre-stroke functioning with mRS and EQ5D, transthoracic echocardiography, ECG and digital 12-lead ECG.
• 6 months: Clinician events of stroke reoccurrence, Brain MRI, mRS, MoCA, EQ5D, ECG and digital 12-lead ECG.
• 24 months: Clinician events of stroke reoccurrence, Brain MRI, mRS, MoCA, EQ5D, ECG and digital 12-lead ECG

Followed by adherence of standard of care treatments.
• Patient Self-Report: Asking the participant directly about their medication-taking habits.
• Pill Counts: Have patients return unused medication, allowing site to calculate how many doses they have taken compared to what was prescribed.
• Pharmacy Refill Records: Review prescription refill history to see if the patient is picking up their medication as prescribed.
• Clinical Assessments: Monitor the participant’s clinical progress. Improvement in symptoms can indicate adherence, although it’s not definitive.
• Support Systems: Implement reminders or support groups (family) to encourage adherence and check in with patients regularly.
Intervention code [1] 329844 0
Treatment: Drugs
Comparator / control treatment
There are two control arms :
1. Control arm for RCT (standard care)- will receive guideline based standard of care treatment as below
2. Patients with atrial myopathy but randomised to the control group-will receive guideline based standard of care treatment as below

standard of care of stroke management of anti-platelet use. National Guidelines based, administration of Aspirin 100mg orally daily, clopidogrel 75 mg orally daily(a combination of both for 3 months and then cease one and continue with one) or
Just Aspirin 100 mg orally daily or
Just clopidogrel 75 mg orally daily, life long

Follow-up :
All participant, either , in RCT or cohort study, will have the same follow-up and observations at Baseline, at 6 months after enrolment, and at 24 months after enrolment
Control group
Active

Outcomes
Primary outcome [1] 339751 0
The primary outcome of the RCT will be encompassing stroke recurrence
Timepoint [1] 339751 0
At Baseline- at the time of enrolment 6 months- 6 months after enrolment 24 months- 24 months after enrolment- primary endpoint
Primary outcome [2] 340227 0
Clinical recurrence of stroke (for both RCT and cohort study)
Timepoint [2] 340227 0
At 6 months post enrolment and at 24 months post enrolment
Primary outcome [3] 340228 0
Imaging recurrence of stroke. (outcome for both RCT and cohort study)
Timepoint [3] 340228 0
At 6 months post enrolment and At 24 months post enrolment
Secondary outcome [1] 441107 0
Secondary outcomes of the RCT will include incidence of disabling stroke (mRS>3),
Timepoint [1] 441107 0
At Baseline- at the time of enrolment 6 months- 6 months after enrolment 24 months- 24 months after enrolment
Secondary outcome [2] 441994 0
Imaging-MRI-Brain : incidence of recurrence of clinical stroke, incidence of recurrence of stroke on imaging, clinical recurrence of stroke events ,
Timepoint [2] 441994 0
at baseline , after enrolment , 6 months after enrolment and at 24 months after emrolment
Secondary outcome [3] 443399 0
MoCA : cognitive function impairment
Timepoint [3] 443399 0
at baseline At 6 months post enrolment and at 24 months post enrolment
Secondary outcome [4] 443400 0
EQ5D : change of quality of life
Timepoint [4] 443400 0
at baseline , at 6 months after enrolment and at 24 months after enrolment.

Eligibility
Key inclusion criteria
1) Patients is at least 18 years old
2) recent ischaemic stroke without major disability (modified Rankin score (mRS) of less than and equal to 3,
3) brain imaging (MRI) evidence of acute infarction that suggests an embolic source
<4 weeks post-event.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Definite cardioembolic stroke due to atrial fibrillation or other identified cardiac source,
2) large artery atherosclerotic stroke (with proximal arterial stenosis) or small vessel (lacunar) stroke,
3) other rare causes of stroke such as arterial dissection, hypercoagulable state,
4)Women of child bearing potential who intend to get pregnant and any breast-feeding and currently pregnant women

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 on computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomisation using tool created on computer
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
1. randomised allocations of Direct Acting Oral Anticoagulant (DOAC) vs standard care for participants with atrial myopathy
2. cohort of participants without atrial myopathy- allocated to national guidelines for standard
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/03/2025
Actual
Date of last participant enrolment
Anticipated
3/03/2028
Actual
Date of last data collection
Anticipated
3/03/2030
Actual
Sample size
Target
750
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC

Funding & Sponsors
Funding source category [1] 317715 0
Government body
Name [1] 317715 0
National Health and Medical Research Council
Country [1] 317715 0
Australia
Primary sponsor type
Government body
Name
hunter new england local health district
Address
Country
Australia
Secondary sponsor category [1] 320033 0
None
Name [1] 320033 0
Address [1] 320033 0
Country [1] 320033 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316407 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 316407 0
Ethics committee country [1] 316407 0
Australia
Date submitted for ethics approval [1] 316407 0
31/10/2024
Approval date [1] 316407 0
20/11/2024
Ethics approval number [1] 316407 0
2024/ ETH02475

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

Contacts
Principal investigator
Name 137790 0
Prof MARK PARSONS
Address 137790 0
Liverpool Hospital , Neurophysiology Department , Corner of Goulburn street and Elizabeth street, Liverpool NSW 2170 .
Country 137790 0
Australia
Phone 137790 0
+61 2 87386512
Fax 137790 0
Email 137790 0
Mark.Parsons@health.nsw.gov.au
Contact person for public queries
Name 137791 0
Jasmeen Khan
Address 137791 0
Liverpool Hospital , Neurophysiology Department , Corner of Goulburn street and Elizabeth street, Liverpool NSW 2170
Country 137791 0
Australia
Phone 137791 0
+61 287386512
Fax 137791 0
Email 137791 0
Jasmeen.Khan@health.nsw.gov.au
Contact person for scientific queries
Name 137792 0
MARK PARSONS
Address 137792 0
Liverpool Hospital , Neurophysiology Department , Corner of Goulburn street and Elizabeth street, Liverpool NSW 2170
Country 137792 0
Australia
Phone 137792 0
+61 2 87386512
Fax 137792 0
Email 137792 0
Mark.Parsons@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only deidentified aggregate analysed data will be available as per the study


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.