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

Phase 2

Completed

• Conditions: Prevention; Stroke
• Interventions: Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Rivaroxaban placebo tablets

• Registration Number: NCT04273516
• Lead Sponsor: Mazandaran University of Medical Sciences

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2020-02-15
• Study First Submitted QC: 2020-02-15
• Study First Posted: 2020-02-18
• Study Start: 2020-08-22
• Primary Completion: 2023-04-10
• Study Completion: 2023-04-30
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-18
• Last Update Posted: 2023-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. signing the inform consent

2. recent ischemic stroke ( 7-60) days with criteria of ESUS

3. only one risk factors of potential embolic source including:

   1. PTFV1 in standard ECG ≥0.05 mm.s or ≥0.005 mv.s
   2. LVH in standard ECG( Sokolow index≥ 35 mm) or on echocardiography
   3. Moderate or severe valvular disorder on echocardiography (except MS)
   4. PFO without indication of occlusion
   5. Left atrium enlargement in echocardiography

Exclusion Criteria

1. History of hypersensitivity to the investigational medicinal product
2. Indication for anticoagulation
3. Indication for dual antiplatelet therapy
4. Contraindication to investigational medications
5. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding
6. Gastrointestinal bleed or major surgery within 3 months
7. Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
8. HAS-BLED score >3
9. Severe non-cardiovascular comorbidity with life expectancy < 3 months
10. Severe renal failure, defined as Glomerular Filtration Rate (GFR) <15ml/min, Dialysis, transplant, Cr >2.26 mg/dL
11. Severe hepatic insufficiency, Cirrhosis or Bilirubin >2x Normal or AST/ALT/AP >3x Normal
12. Modified Rankin Scale of >=4 at time of randomization or inability to swallow medications.
13. Hemorrhagic transformation of infarction detected by Brain CT or MRI at the time of drug application
14. Radiological or microbiological evidence of COVID-19 infection

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Rivaroxaban 2.5 Mg Oral Tablet	Tablet Rivaroxaban 2.5 mg 2 times daily plus ASA 80 mg daily
Comparator	Rivaroxaban placebo tablets	Tab ASA 80 mg daily plus placebo ( similar to rivaroxaban tablet) 2 times daily

Primary Outcome Measures

Name	Time	Method
Rate of stroke recurrence	Rate of stroke recurrence during one year fallow up	Number of stroke events during 1 year of study
Rate of major bleeding	During 1 year of study	Rate of major bleeding according to criteria of the International Society of Thrombosis and Hemostasis

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Bou- Ali Sina Hospital; 🇮🇷 Sari, Mazandaran, Iran, Islamic Republic of