StrokePhase 2/3AREST-ESUSNCT04273516
Rivaroxaban Plus ASA in Embolic Stroke of Undetermined Source(AREST-ESUS)
A Phase 2/3 study testing Rivaroxaban 2.5 Mg Oral Tablet in people with Stroke and Prevention, run by Mazandaran University of Medical Sciences at 1 site in Iran.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Prevention
- What is being tested?
- Rivaroxaban 2.5 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteIran
- Study dates
- 22 Aug 2020to 30 Apr 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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
- Conditions
- Stroke, Prevention
- Being tested
- Rivaroxaban 2.5 Mg Oral Tablet, Rivaroxaban placebo tablets
- Keywords
- ESUS, DOACS, Prevention
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban 2.5 Mg Oral TabletDrug
Also called Axabin 2.5
Tablet Rivaroxaban 2.5 mg 2 times daily add to standard treatment ASA 80 mg daily
Rivaroxaban placebo tabletsDrug
Also called Placebo
Placebo tablets add to ASA 80 mg daily that is standard treatment
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Tablet Rivaroxaban 2.5 mg 2 times daily plus ASA 80 mg daily Receives: Drug: Rivaroxaban 2.5 Mg Oral Tablet |
| Comparator | Placebo comparator | Tab ASA 80 mg daily plus placebo ( similar to rivaroxaban tablet) 2 times daily Receives: Drug: Rivaroxaban placebo tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of stroke recurrence
Number of stroke events during 1 year of study
Measured: 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
Measured: During 1 year of study
Secondary outcomes (5)
Rate of stroke or systemic embolisms
Number of stroke or systemic embolisms recurrence during 1 year of study
Measured: During 1 year of study
Mortality rate
Number of all cause mortality during study
Measured: 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
Measured: During 1year of study
Rate of intracranial bleeding
Rate of ICH during study
Measured: During 1year of study
Rate of fatal bleeding
Rate of fatal bleeding in any site
Measured: During 1 year of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2020
- Study start22 Aug 2020
- Primary completion10 Apr 2023
- Study completion30 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mazandaran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Athena Sharifi Razavi, Mazandaran University of Medical Sciences
- Investigators
- Athena Sharifi-Razvi, Principal investigator, mazandaran university of medical scienceMonireh Ghazaeian, Study director, mazandaran university of medical science
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04273516
- Sponsor's protocol ID
- 3498
- Acronym
- AREST-ESUS
- Status last verified
- Oct 2023
- First submitted
- 15 Feb 2020
- Last updated
- 19 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Ghazaeian M, Ramzanpour F, Sharifi-Razavi A. Aspirin plus rivaroxaban efficacy and safety in embolic stroke of undetermined source: A randomized, placebo-controlled, outcome assessor-blind, feasibility study. Clin Neurol Neurosurg. 2025 Mar;250:108813. doi: 10.1016/j.clineuro.2025.108813. Epub 2025 Feb 28.
PubMed 40037214
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aspirin Plus Rivaroxaban Efficacy and Safety in Embolic Stroke of Undetermined Source: A Randomized, Placebo Controlled, Outcome Assessor Blind, Feasibility Study
- ClinicalTrials.gov ID
- NCT04273516
- Acronym / sponsor ID
- AREST-ESUS / 3498
- Conditions
- Stroke, Prevention
- Keywords
- ESUS, DOACS, Prevention
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Mazandaran University of Medical SciencesUniversity, hospital or other
- Study start
- 22 Aug 2020 (actual)
- Primary completion
- 10 Apr 2023 (actual)
- Study completion
- 30 Apr 2023 (actual)
- First posted
- 18 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Rivaroxaban 2.5 Mg Oral TabletTablet Rivaroxaban 2.5 mg 2 times daily plus ASA 80 mg daily |
| Comparator | Placebo comparator | Drug: Rivaroxaban placebo tabletsTab ASA 80 mg daily plus placebo ( similar to rivaroxaban tablet) 2 times daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- signing the inform consent
- recent ischemic stroke ( 7-60) days with criteria of ESUS
- only one risk factors of potential embolic source including:
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban 2.5 Mg Oral TabletAlso: Axabin 2.5Tablet Rivaroxaban 2.5 mg 2 times daily add to standard treatment ASA 80 mg daily | Drug | Intervention |
| Rivaroxaban placebo tabletsAlso: PlaceboPlacebo tablets add to ASA 80 mg daily that is standard treatment | Drug | Comparator |
Primary outcome
Rate of stroke recurrence
Time frame: Rate of stroke recurrence during one year fallow up
Number of stroke events during 1 year of study
Rate of major bleeding
Time frame: During 1 year of study
Rate of major bleeding according to criteria of the International Society of Thrombosis and Hemostasis
5 secondary outcomes
Rate of stroke or systemic embolisms
Time frame: During 1 year of study
Mortality rate
Time frame: During 1year of study
Rate of non-major bleeding
Time frame: During 1year of study
Rate of intracranial bleeding
Time frame: During 1year of study
Rate of fatal bleeding
Time frame: During 1 year of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2023.
- Derived from this study: PubMed 40037214Ghazaeian M, Ramzanpour F, Sharifi-Razavi A. Aspirin plus rivaroxaban efficacy and safety in embolic stroke of undetermined source: A randomized, placebo-controlled, outcome assessor-blind, feasibility study. Clin Neurol Neurosurg. 2025 Mar;250:108813. doi: 10.1016/j.clineuro.2025.108813. Epub 2025 Feb 28.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Athena Sharifi-Razvi principal investigator
mazandaran university of medical science
Monireh Ghazaeian study director
mazandaran university of medical science
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rivaroxaban 2.5 Mg Oral Tablet in people with Stroke and Prevention, run by Mazandaran University of Medical Sciences at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of stroke recurrence (time frame: Rate of stroke recurrence during one year fallow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04273516, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2023.