Clinical trial NCT01923818: Treatment of Rivaroxaban Versus Aspirin for Non-disabling Cerebrovascular Events
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Ischemic Stroke
TIA
Keywords: rivaroxaban
aspirin
new oral anticoagulant
TIA
acute minor ischemic stroke
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2013-08-16
Enrollment: 3700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: percentage of patients with new stroke (ischemic or hemorrhage)
timeFrame: 90 days
Secondary outcomes:
measure: Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)
timeFrame: 30 days
measure: mRS score changes (continuous) and dichotomized at percentage with score 0 to 2 versus 3 to 6
timeFrame: 30 days and 90 days
measure: Changes in NIHSS scores
timeFrame: 90 days
measure: moderate to severe bleeding events
timeFrame: 90 days
measure: Total mortality
timeFrame: 90 days
measure: Adverse events/severe adverse events reported by the investigators
timeFrame: 90 days
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
Study officials:
affiliation: Neurology Department,Xijing Hospital
name: Gang Zhao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yang F, Jiang W, Bai Y, Han J, Liu X, Zhang G, Zhao G. Treatment of Rivaroxaban versus Aspirin for Non-disabling Cerebrovascular Events (TRACE): study protocol for a randomized controlled trial. BMC Neurol. 2015 Oct 12;15:195. doi: 10.1186/s12883-015-0453-7.