Branch Atheromatous Disease Clinical Trial
Official title:
Study on Tirofiban With Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction: A Randomized, Double-blinded, Placebo-controlled, Multi-center Trial
Perforating artery territorial infarction (PAI) refers to a single ischaemic lesion <20 mm in a single perforating arterial territory and branch atheromatous disease (BAD) is a important etiological factor. BAD related infarction accounts for 10%-15% ischemic cerebral infarction and is closely related to early neurological deterioration (END). Among patients with BAD, dual antiplatelet (clopidogrel plus aspirin) did not significantly reduce the risk of recurrent stroke. The primary purpose of this study is to assess the efficacy and safety of tirofiban combined with aspirin versus placebo combined with aspirin in reducing the risk of recurrence and progression of stroke at 90 days in patients with acute penetrating artery territory infarction.
Perforating artery territorial infarction (PAI) constitute about 25% of ischemic strokes, including three pathophysiological mechanisms - lipohyalinosis, microatheroma and large parent artery plaque. The latter two are prone to stroke recurrence and early neurological deterioration. Aspirin plus clopidogrel are effective antiplatelet therapy for PAI patients with parent artery stenosis, but controversial in patients with branch atheromatous disease (BAD). Early rapid initiation of platelet aggregation inhibitors, such as Tirofiban, a GPIIb/IIIa receptor antagonist, may benefit those patients. The primary purpose of this study is to assess the efficacy and safety of tirofiban combined with aspirin versus placebo combined with aspirin in reducing the risk of recurrence and progression of stroke at 90 days in patients with acute penetrating artery territory infarction caused by BAD. This is a prospective, randomized, multicenter, double-blind clinical trial. In 40 centers in China, 970 patients with the following situations will be enrolled: single acute infarction of penetrating artery territory within 48 hours of onset, which involves at least 2 axial layers, or whose maximum diameter ≥15mm, or connected to the ventral surface of the median pons without crossing the midline on DWI image, no severe stenosis (defined as > 70%) of parent artery. Patients will be randomly assigned into 2 groups according to the ratio of 1:1: 1. Tirofiban (Day 1) + Aspirin (Day 1-90) 2. Placebo (Day 1) + Aspirin (Day 1-90) Face to face interviews will be made on baseline, 24 hours after randomization, day 7 after randomization, discharge day, and day 90 after randomization. Survival curves will be estimated for the primary outcome using the Kaplan-Meier procedure and compared using a Cox regression model Wald test, stratified by the opposite arm of the factorial design. Safety outcomes will be calculated using the Kaplan-Meier curve to simulate the 3-month cumulative risk, and the Cox proportional hazards model to calculate the HR and 95% confidence interval. The primary endpoints include recurrent stroke and early progression of stroke. The secondary endpoints include composite vascular events (stroke, myocardial infarction, and cardiovascular death), disability or death (mRS 2-6), improvement of neurological function and EQ-5D score. The safety endpoints include severe hemorrhage events, symptomatic and non-symptomatic intracranial hemorrhage, moderate hemorrhage, vascular death, overall mortality and (serious) adverse event. ;