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The primary goal of the clinical trial is to test the effect of oral rivaroxaban plus aspirin in patients with recent stroke/ transient ischemic attack (TIA) caused by intracranial artery stenosis. Participants will be divided into 2 groups to receive either oral rivaroxaban plus aspirin or oral clopidogrel plus aspirin. The main question it aims to answer is whether the experimental group (oral rivaroxaban plus aspirin) is superior to the control group ( oral clopidogrel plus aspirin) to lower recurrent stroke/TIA or death in these patients during 1 year of follow-up.
Full description
Intracranial atherosclerotic stenosis (ICAS) accounts for up to 30-50% of strokes amongst Asian patient cohorts, in contrast to 5-10% of strokes amongst western patient cohorts. The SAMMPRIS established aggressive medical management (dual antiplatelet therapy using asprin and clopidogrel, intensive management of vascular risk factors, and lifestyle modification) as a superior choice for symptomatic ICAS compared to the percutaneous transluminal angioplasty and stenting. However, around 15% still had recurrent stroke or death during a median follow-up of 32.4 months in SAMMPRIS study in the aggressive medical management group.
Rivaroxaban is a Non-vitamin K antagonist oral anticoagulant (NOAC) that Directly and selectively inhibits factor Xa. 2019 European Society of Cardiology (ESC) recommended that adding rivaroxaban (2.5mg twice a day) to aspirin for long-term secondary prevention in patients with chronic coronary syndromes (post-myocardial infarction >1 year) may be considered (IIB). 2020 ESC also recommended the adding of rivaroxaban (2.5mg twice a day for 1 year) to aspirin plus clopidogrel in acute coronary syndrome (IIB).
The proposed study will directly compare rivaroxaban on top of aspirin with clopidogrel on top of asprin for preventing recurrent stroke/TIA and death in recent stroke/TIA patients with ICAS.
The investigators calculated that a sample of 1180 patients (590 in each arm) would provide 80% power to detect a relative risk reduction of 35% in the ravaxaban-aspirin group, with a two-sided type I error of 0.05, assuming an event rate of 15% in the clopidogrel-aspirin group and a 5% overall rate of withdrawal.
Baseline features of the two groups were compared with the use of an independent group t-test (for means) or chi-square test (for percentages). Analysis of primary and secondary outcomes was based on Kaplan-Meier estimates of cumulative incidence. All analyses were performed on an intention-to-treat basis, unless specified otherwise. All tests were two-sided, and a P value of 0.05 was considered to indicate statistical significance. All statistical analyses were performed with the use of SPSS software.
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Inclusion criteria
Age ≥ 30 years and ≤ 75 years
TIA or Acute ischemic stroke that occurred within 30 days prior to randomization.
Modified Rankin score of ≤ 3
TIA or Acute ischemic stroke attributed to a 50 to 99% stenosis of a major intracranial artery (internal carotid artery [ICA], vertebral artery [VA], basilar artery [BA] and the M1 segment of middle cerebral artery [MCA]). The diagnostic evaluation for ICAS at each site is confirmed by the local investigator, using magnetic resonance angiography (MRA), or computerized tomographic angiography (CTA), high resolution MR, or digital substraction angiography (DSA).
To increase the likelihood that the symptomatic intracranial stenosis is atherosclerotic, patients aged 30-49 years are required to meet at least one additional criteria (i-vi) below:
i. insulin dependent diabetes for at least 15 years. ii. at least 2 of the following atherosclerotic risk factors: hypertension (blood pressure ≥ 140/90 or on antihypertensive therapy); dyslipidemia (low density lipoprotein [LDL] ≥ 130 mg /dl or high density lipoprotein [HDL] < 40 mg/dl or fasting triglycerides ≥150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event.
iii. history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease.
iv. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic. v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography.
vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic.
Patient agrees with follow-up visits and is available by phone.
Patient understands the purpose and requirements of the study, can make him/herself understood, and has signed informed consent.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
1,180 participants in 2 patient groups
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Central trial contact
Zhaolu Wang, Doctor; Kezhong Zhang, Doctor
Data sourced from clinicaltrials.gov
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