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

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

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

Study Overview

• Status: Completed
• Conditions: Stroke; Prevention
• Intervention / Treatment: Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Rivaroxaban placebo tablets

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Mazandaran
    • Sari, Mazandaran, Iran, Islamic Republic of
      • Bou- Ali Sina Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mazandaran University of Medical Sciences
• Investigators: Principal Investigator: Athena Sharifi-Razvi, mazandaran university of medical science; Study Director: Monireh Ghazaeian, mazandaran university of medical science

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2020
• Primary Completion (Actual): April 10, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: February 15, 2020
• First Submitted That Met QC Criteria: February 15, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Prevention; ESUS; DOACS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ischemic Stroke; Stroke; Embolic Stroke; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 3498

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Access Criteria: Data will be available for researchers and scientific persons after request and review the proposal .
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes