The CMOSS-2 trial is a government-funded, prospective, multicenter, randomized controlled trial. It will recruit symptomatic chronic occlusion of the middle cerebral artery in patients with severe hemodynamic insufficiency. Only high-volume center with a proven track record will be included. Patients will be randomized (1:1) to best medical treatment alone or medical treatment plus bypass surgery. Primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.

Middle cerebral artery occlusion is an important cause of ischemic stroke, and there are currently two treatment methods: medical treatment alone and extracranial-intracranial bypass surgery (EC-IC bypass surgery). Previous studies have shown that the optimal medical treatment has an annual stroke recurrence rate of up to 10%, and patients with concomitant hemodynamic disorders can also increase by 7.3 times.

The CMOSS study was the first trial in China to evaluate the safety and efficacy of EC-IC bypass surgery on patients with ICA or MCA occlusion combined with hemodynamic insufficiency evaluated with CT perfusion. The results showed that there was no significant difference in the risk of stroke or death between the bypass group and the medical group, but there was a significant difference in ipsilateral ischemic stroke between 30 days and 2 years after randomization, with only 2.0% in the surgery group and 10.3% in the medical group; In addition, subgroup analysis found that for patients with MCA occlusion or severe hemodynamic insufficiency, bypass surgery has a potential beneficial trend over medical treatment alone.

The CMOSS-2 trial is a government-funded, prospective, multicenter, randomized controlled trial. It will recruit symptomatic chronic occlusion of the middle cerebral artery in patients with severe hemodynamic insufficiency. Only high-volume center with a proven track record will be included. Patients will be randomized (1:1) to best medical treatment alone or medical treatment plus bypass surgery. Primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization. The CMOSS-2 trial will be conducted in 13 sites in China.

Inclusion Criteria:

1. Age of 18-65 years;
2. Confirmed as chronic occlusion of unilateral middle cerebral artery (MCA) by digital subtraction angiography (DSA) or computed tomography angiography (CTA). Other cerebral artery stenosis should be less than 50%.
3. CT perfusion demonstrates severe hemodynamic insufficiency in the territory of the qualifying MCA with MTT (symptomatic side) ≥ 6s or rCBF (symptomatic side/contralateral side) ≤ 0.8;
4. mRS score is 0-2 points;
5. A history of ischemic events (including<1/2 cerebral infarction in the middle cerebral artery supply area, or transient ischemic attack [TIA]) related to the qualifying artery within 12 months ;
6. The onset of acute stroke should be more than 1 month;
7. CT or MRI excludes large cerebral infarction (infarction>1/2 of the territory of the qualifying middle cerebral artery);
8. Patients or their guardians voluntarily participate of the study and sign the consent form.

Exclusion Criteria:

1. History of intracranial hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, or extradural hemorrhage within 6 weeks;
2. Unstable angina pectoris or myocardial infarction, congestive heart failure within 6 months;
3. Women who are pregnant or lactating;
4. Coagulation dysfunction or hemorrhagic tendency (e.g. INR > 1.5 and/or platelet count < 100,000 mcL);
5. Other diseases with a life expectancy of less than 2 years
6. Previous treatment with EC-IC bypass surgery
7. Known allergy or contraindication to aspirin or clopidogrel or other antiplatelet drugs.
8. Known cardiac conditions that may lead to cardiogenic embolism: including prosthetic valves, infective endocarditis, left atrial or left ventricular thrombosis, atrial fibrillation, sick sinus node syndrome, atrial mucinous tumor or cardiomyopathy, ejection fraction <25%;
9. Allergy to iodine or x-ray contrast, blood creatinine > 3.0 mg/dl or other contraindications to arteriography
10. Uncontrolled diabetes mellitus with fasting blood sugar (FBS) >16.7 mmol/L
11. Uncontrolled hypertension with a sitting systolic blood pressure >180 mmHg or a sitting diastolic blood pressure >110 mmHg;
12. Persistent worsening of neurological symptoms within 72 hours;
13. Severe liver dysfunction, defined as serum alanine transaminase (ALT) and/or glutamic oxalacetic transaminase (AST) > 3 times the upper limit of normal range;
14. Active peptic ulcer disease;
15. Having received a clinical trial drug or device within 30 days prior to screening, or being enrolled in another clinical trial;
16. Other diseases or medical history that, in the judgment of the investigator, may affect the efficacy or safety evaluation of this study.