Perforating artery territorial infarction (PAI) refers to a single ischemic lesion in a single perforating arterial territory and branch atheromatous disease (BAD) is an important type. BAD related stroke accounts for 10%-15% ischemic cerebral infarction and is closely related to early neurological deterioration (END). Among patients with single ischemic lesion in other study, 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 stroke and END in patients with BAD.

Branch atheromatous disease (BAD) was characterized by cerebral infarction within penetrating artery territories. It arises from atherosclerotic stenosis or occlusion at the origin or proximal segment of these arteries, with three principal pathological manifestations. BAD is the typical etiology of the isolated infarction in penetrating artery territories. There is still no consensus on the classification, and both the TOAST and the CISS (Chinese ischemic stroke subclassification) have the limitations.

Currently, there are no evidence-supported, guideline-based on how to prevent the END of BAD. Combining the pathology of atherosclerosis, we hypothesize that short-term use of tirofiban with aspirin for intensive antiplatelet therapy may confer benefits.

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 END and stroke at 90 days in patients with BAD.

This is a prospective, randomized, multicenter, double-blind clinical trial. In China, 970 patients with the following criteria will be enrolled: single acute infarction of penetrating artery territory (maximum diameter <30 mm on DWI of MRI) within 48 hours, which involves two or more transverse layers, or whose maximum diameter ≥15 mm, , 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:

1. Tirofiban + Aspirin (Day 1-90)
2. Placebo + Aspirin (Day 1-90) Interviews will be made on baseline, 24 hours after randomization, day 7 after randomization, discharge day, and day 90 after randomization.

Inclusion Criteria:

1. 18-80 years old;
2. Male or female;
3. Within 48 hours of onset;
4. Clinical symptoms and signs suggest acute single infarction of penetrating artery territory (no cortical involvement, no multifocal involvement, NIHSS ≤10 and consciousness-1a ≤1);
5. DWI suggests single infarction (diameter < 30mm) of penetrating artery territory which involves at least 2 axial layers, or its maximum diameter ≥15mm, or it is connected to the ventral surface of the pons, closing to but not crossing the midline, and located in one side;
6. No severe stenosis (defined as <70%) of parent artery;
7. The patient or his / her legal representative is able and willing to sign the informed consent.

Exclusion Criteria:

1. History of intracranial hemorrhage
2. History of intracranial tumors, cerebral arteriovenous malformation, or aneurysm;
3. Emergency endovascular intervention or intravenous thrombolysis before randomization;
4. Dual antiplatelet therapy currently or within 14 days of randomization (excluding use of aspirin and clopidogrel after onset without loading dose of clopidogrel);
5. Use of other antiplatelet drugs (ticagrelor, cilostazol, etc.), anticoagulant drugs, snake venom, defibrase, lumbrukinase or other defibrase treatments after onset;
6. Expected long-term use of non-investigational antiplatelet drugs or non-steroidal anti-inflammatory drugs;
7. With severe stenosis (> 70%) of parent artery giving off responsible penetrating artery;
8. Definite indications for anticoagulation (suspicion of cardioembolism, e.g. atrial fibrillation, known heart valve prosthesis, atrial myxoma, endocarditis, etc.) or indications for dual antiplatelet therapy (e.g. recent coronary or cerebral artery stent implantation);
9. Severe hepatic or renal insufficiency before randomization (severe hepatic insufficiency refers to ALT or AST > 3 times the upper limit of normal; severe renal insufficiency refers to creatinine clearance rate (CCr) < 30ml/min);
10. Hemorrhagic tendency (including but not limited to)：PLT<100×10^9/L; heparin treatment within 48h; APTT ≥ 35s; current use of warfarin, INR > 1.7; current use of novel oral anticoagulants; current use of direct thrombin or factor Xa inhibitor;
11. Resistant hypertension which could not be controlled by medicine (SBP > 180mmHg or DBP > 110mmHg);
12. History of obvious head trauma within three months of randomization;
13. History of intracranial or intramedullary surgery within three months of randomization;
14. History of major surgery or severe physical trauma within one month of randomization;
15. Severe neurological defects (mRS ≥ 2) before the onset;
16. Acute pericarditis;
17. Hemorrhagic retinopathy;
18. Childbearing-age women who do not take effective methods of contraception without negative records of pregnancy tests;
19. Known to be allergic to tirofiban;
20. Other surgical or interventional therapy planned within 3 months requiring experimental drugs discontinuation;
21. Life expectancy < 6 months due to any terminal illness;
22. Patients who are undergoing experimental drugs or instruments;
23. Other conditions which suggest participants are unsuitable for this study, e.g. mental diseases, cognitive or mood disturbance,and could not comply with research procedures or with MRI contraindications.