Treatment of Rivaroxaban Versus Aspirin for Non-disabling Cerebrovascular Events (TRACE)

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

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.

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.

• Ischemic Stroke
• TIA

• Drug: rivaroxaban
  orally active direct factor Xa inhibitor
  Other Names:

  • BAY 59-7939
  • Xarelto
• Drug: Aspirin
  non-steroidal anti-inflammatory drugs
  Other Name: Acetylsalicylic acid
• Drug: placebo

• Active Comparator: aspirin
  Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30
  Interventions:

  • Drug: Aspirin
  • Drug: placebo
• Experimental: Rivaroxaban 5mg
  Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30
  Interventions:

  • Drug: rivaroxaban
  • Drug: placebo
• Experimental: rivaroxaban 10mg
  Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30
  Interventions:

  • Drug: rivaroxaban
  • Drug: placebo

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)