Treatment of Rivaroxaban Versus Aspirin for Non-disabling Cerebrovascular Events

Study Overview
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Brief Summary
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Transient ischemic attack (TIA) or minor ischemic stroke has a high risk of early recurrent stroke. As the golden standard, aspirin effect modestly on acute ischemic stroke, and slightly increase the risk of intracerebral hemorrhage. Recently, rivaroxaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants, while carrying significantly less risk of intracranial hemorrhage. The TRACE trial is a randomized, double-blind, multicenter, controlled clinical trial in China. The investigators will assess the hypothesis that a 30-days rivaroxaban regimen is superior to aspirin alone for the treatment of high-risk patients with acute nondisabling cerebrovascular event.

Detailed Description
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The TRACE study is a randomized, double-blind clinical trial with a target enrollment of 3,700 Chinese patients. Two subtypes of patients will be enrolled: I, acute disabling ischemic stroke (<24 hours of symptoms onset); II, acute TIA (<24 hours of symptoms onset). Patients will be randomized into 3 groups: Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30 Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 The primary efficacy end point is percentage of patients with new stroke (ischemic or hemorrhage) at 90 days.

Official Title
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Randomized,Double-blind Trial Comparing the Effects of a Rivaroxaban Regimen During the First 30 Days,Versus Aspirin for the Acute Treatment of TIA or Minor Stroke

Conditions
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Ischemic Stroke, TIA

Intervention / Treatment
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* Drug: rivaroxaban
* Drug: Aspirin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects (male or female ≥18 years old) Acute nondisabling ischemic stroke (NIHSS ≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the last see normal principle TIA (neurologic deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with investigational medication within 24 hours of symptoms onset. Symptom onset is defined by the last see normal principle Informed consent signed Exclusion Criteria: Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major nonischemic brain disease, on baseline head CT or MRI scan mRS score >2 at randomization (premorbid historical assessment) NIHSS ≥4 at randomization Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state) Contraindication to investigational medications Thrombolysis for ischemic stroke within preceding 7 days History of intracranial hemorrhage Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anticoagulation Gastrointestinal bleed or major surgery within 3 months Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months TIA or minor stroke induced by angiography or surgery Severe noncardiovascular comorbidity with life expectancy <3 months Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test result Severe renal failure, defined as Glomerular Filtration Rate (GFR) <30 ml/min Severe hepatic insufficiency (Child-Pugh score B to C)

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: aspirin<br>Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30 | Drug: Aspirin<br>* non-steroidal anti-inflammatory drugs<br>* Other names: Acetylsalicylic acid;Drug: placebo<br> <br> |
| Experimental: Rivaroxaban 5mg<br>Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 | Drug: rivaroxaban<br>* orally active direct factor Xa inhibitor<br>* Other names: Xarelto;Drug: placebo<br> <br> |
| Experimental: rivaroxaban 10mg<br>Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 | Drug: rivaroxaban<br>* orally active direct factor Xa inhibitor<br>* Other names: Xarelto;Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients with new stroke (ischemic or hemorrhage) |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) |  | 30 days | 
| mRS score changes (continuous) and dichotomized at percentage with score 0 to 2 versus 3 to 6 |  | 30 days and 90 days | 
| Changes in NIHSS scores |  | 90 days | 
| moderate to severe bleeding events |  | 90 days | 
| Total mortality |  | 90 days | 
| Adverse events/severe adverse events reported by the investigators |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rivaroxaban, aspirin, new oral anticoagulant, TIA, acute minor ischemic stroke