Trial of PCSK9 Inhibition in Patients with Acute Stroke and Symptomatic Intracranial Atherosclerosis

Inclusion Criteria:

• Clinical diagnosis of ischemic stroke with National Institutes of Health StrokeScale (NIHSS) score of 1-15

• Ischemic lesions on diffuse-weighted imaging located in the territory of symptomaticintracranial atherosclerosis (ICAS).

• Symptomatic ICAS (above 30%) at the M1 or M2 of the middle cerebral artery, basilarartery or at the intracranial portion of the internal carotid artery or vertebralartery.

• Serum LDL-C ≥70 mg/dL for subjects on lipid-lowering therapies (such as a statinand/or ezetimibe) or LDL-C ≥100 mg/dL for subjects without lipid-lowering therapies.

• Ability to randomize within 7 days of time last known free of new ischemic symptoms.

• Ability to receive alirocumab or statin treatment within 7 days of stroke onset.

• Head CT or MRI ruling out hemorrhage or other pathology, such as vascularmalformation, tumor, or abscess, that could explain symptoms or contraindicatetherapy.

• Pre-stroke modified Rankin Scale (mRS)≦2

Exclusion Criteria:

• Age <20 years.

• Judged by clinical physician.

• After endovascular intervention or endarterectomy for the symptomatic ICAS.

• Patients with more than 50% stenosis of extra-cranial arteries the relevant arterieson magnetic resonance angiography (MRA), including extra-cranial carotid artery orvertebral arteries.

• Patients with high risk of cardioembolic source, such as atrial fibrillation, acutemyocardial infarction, severe heart failure or valvular heart disease.

• Other determined stroke etiology, such as vasculitis, shock, antiphospholipidantibody syndrome, arterial dissection, CADASIL and etc.

• Qualifying ischemic event induced by angiography or surgery.

• Severe non-cardiovascular comorbidity with life expectancy <6 months.

• Contraindication or allergy to alirocumab or Gadolinium

• Severe renal (serum creatinine >2 mg/dL) or calculated glomerular filtration rate <30 mL/min/ 1.73 m2 by estimated glomerular filtration rate (eGFR) using CockcroftGault methodology.

• Hepatic insufficiency (INR>1.2; ALT>40 U/L or any resultant complication, such asvariceal bleeding, encephalopathy, or jaundice)

• Hemostatic disorder or systemic bleeding in the past 3 months

• Current thrombocytopenia (platelet count <100 x109/L) or leukopenia (<2 x109/L)

• Anemia（<10 mg/dL）

• History of drug-induced hematologic or hepatic abnormalities

• History of malignancy that required surgery, radiation therapy or systemic therapy.

• Females who are pregnant or nursing, or who are of childbearing potential andunwilling to use effective contraception.

• Other neurological conditions that would complicate assessment of outcomes duringfollow-up.