Rivaroxaban Plus ASA in Embolic Stroke of Undetermined Source(AREST-ESUS)

Study Overview
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Brief Summary
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Approximately 17% of all patients with stroke are classified as having ESUS, which is associated with a considerable rate of stroke recurrence 4-5 % per year. Despite recent scientific advances in acute ischemic stroke treatment in recent decades,consensus treatment of all guidelines is still ASA

Detailed Description
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This is an outcome assessor blind, randomized, parallel, placebo-controlled pilot study on ischemic stroke of undetermined source which will be conducted in Bu Ali Sina hospital in Sari, Iran. Patients with recent stroke with criteria of ESUS, will be randomized to Rivaroxaban 2.5 mg BID plus ASA 80 mg daily or ASA 80 mg plus placebo (1:1 ratio) and have visit every 3 month until 1 year

Official Title
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Aspirin Plus Rivaroxaban Efficacy and Safety in Embolic Stroke of Undetermined Source: A Randomized, Placebo Controlled, Outcome Assessor Blind, Feasibility Study

Conditions
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Stroke, Prevention

Intervention / Treatment
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* Drug: Rivaroxaban 2.5 Mg Oral Tablet
* Drug: Rivaroxaban placebo tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signing the inform consent recent ischemic stroke ( 7-60) days with criteria of ESUS only one risk factors of potential embolic source including: PTFV1 in standard ECG ≥0.05 mm.s or ≥0.005 mv.s LVH in standard ECG( Sokolow index≥ 35 mm) or on echocardiography Moderate or severe valvular disorder on echocardiography (except MS) PFO without indication of occlusion Left atrium enlargement in echocardiography Exclusion Criteria: History of hypersensitivity to the investigational medicinal product Indication for anticoagulation Indication for dual antiplatelet therapy Contraindication to investigational medications History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding Gastrointestinal bleed or major surgery within 3 months Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months HAS-BLED score >3 Severe non-cardiovascular comorbidity with life expectancy < 3 months Severe renal failure, defined as Glomerular Filtration Rate (GFR) <15ml/min, Dialysis, transplant, Cr >2.26 mg/dL Severe hepatic insufficiency, Cirrhosis or Bilirubin >2x Normal or AST/ALT/AP >3x Normal Modified Rankin Scale of >=4 at time of randomization or inability to swallow medications. Hemorrhagic transformation of infarction detected by Brain CT or MRI at the time of drug application Radiological or microbiological evidence of COVID-19 infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Tablet Rivaroxaban 2.5 mg 2 times daily plus ASA 80 mg daily | Drug: Rivaroxaban 2.5 Mg Oral Tablet<br>* Tablet Rivaroxaban 2.5 mg 2 times daily add to standard treatment ASA 80 mg daily<br>* Other names: Axabin 2.5;|
| Placebo Comparator: Comparator<br>Tab ASA 80 mg daily plus placebo ( similar to rivaroxaban tablet) 2 times daily | Drug: Rivaroxaban placebo tablets<br>* Placebo tablets add to ASA 80 mg daily that is standard treatment<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of stroke recurrence | Number of stroke events during 1 year of study | Rate of stroke recurrence during one year fallow up | 
| Rate of major bleeding | Rate of major bleeding according to criteria of the International Society of Thrombosis and Hemostasis | During 1 year of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of stroke or systemic embolisms | Number of stroke or systemic embolisms recurrence during 1 year of study | During 1 year of study | 
| Mortality rate | Number of all cause mortality during study | During 1year of study | 
| Rate of non-major bleeding | Rate of non-major bleeding according to criteria of the International Society of Thrombosis and Hemostasis | During 1year of study | 
| Rate of intracranial bleeding | Rate of ICH during study | During 1year of study | 
| Rate of fatal bleeding | Rate of fatal bleeding in any site | During 1 year of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESUS, DOACS, Prevention