Phase III Clinical Trial of SHPL-49 Injection in the Treatment of Acute Ischemic Stroke

Inclusion Criteria:

1. Age 18-80 years old (including upper and lower limits);

2. Clinically diagnosed as acute ischemic stroke according to the latest guidelines;

3. Patients diagnosed as acute ischemic stroke who plan to receive or have receivedstandard intravenous thrombolysis in hospital (this research center) within 8hoursof symptom onset;

4. Patients who have NIHSS score≥5 and ≤ 22 before thrombolysis;

5. Pre-stroke mRS score ≤1;

6. Patients or legally authorized representatives who are able and willing to signinformed consent.

Exclusion Criteria:

1. Complicated with intracranial hemorrhagic diseases, including hemorrhagic stroke,epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoidhemorrhage, etc.;

2. Severe disturbance of consciousness: patients with NIHSS 1a consciousness level itemscore ≥2;

3. Cerebral Computed tomography (CT) or Magnetic resonance imaging (MRI) indicated alarge anterior circulation cerebral infarction (infarct area greater than 1/3 of themiddle cerebral artery blood supply area);

4. Stroke with rapid improvement of symptoms before intravenous thrombolysis, or acuteischemic symptoms suspected to be caused by other causes;

5. Patients who are ready to receive or have received endovascular therapy;

6. After the onset of the disease, the drugs with neuroprotective effects which havebeen used: commercially available Edaravone, Edaravone and Dexborneol,Butylphthalide, Citicoline, Nimodipine, Ganglioside, Human Urinary Kallidinogenase,Cinepazide, Cattle Encephalon Glycoside and Ignotin, Fasudil, Compound PorcineCerebroside and Ganglioside, Piracetam, Oxiracetam, Mouse Nerve Growth Factor ForInjection, Cerebrolysin, Deproteinised Calf Blood Serum Injection, DeproteinisedCalf Blood Extractives Injection, Ginkgolides Injection, Ginkgolides DiterpeneLactone Meglumine Injection, Ginkgo Leaf Extract and Dipyridamole Injection, Extractof Ginkgo Biloba Leaves Injection, Safflower Extract and Aceglutamide Injection,Xuesaitong Injection, Xuesaitong Soft Capsules, and injections containing any singleeXtract of Chuanxiong (Chuanxiong Rhizoma), Danshen (Salviae Miltiorrhizae Radix ETRhizoma), Hongjingtian (Rhodiolae Crenulatae Radix Et Rhizoma),or several of theseChinese herbal ingredients;

7. Patients with a history of atrial fibrillation, deep vein thrombosis of the lowerextremities, pulmonary embolism or other conditions that require the use ofanticoagulant drugs during administration;

8. Severe hypertension: systolic blood pressure ≥180mmHg or diastolic blood pressure ≥100mmHg after taking antihypertensive drugs before thrombolysis;

9. Severe renal insufficiency: serum creatinine >2 times upper limit of normal orcreatinine clearance (CLcr) < 30mL/min (Cockcroft-Gault formula), or with otherknown severe renal insufficiency such as renal failure and uremia ; (Note: CockcroftGault formula: (1) Male: CLcr (mL/min) = [140 - age (yrs)]× body weight (kg) / [0.814 × serum creatinine (μmol/L)]; (2) female: CLcr (mL/min) = {[140 - age (yearsold)] by weight (kg) / [0.814 x serum creatinine (μmol/L)]} x 0.85);

10. Severe hepatic function impairment: Alanine aminotransferase (ALT) or Aspartateaminotransferase(AST) 3 times upper limit of normal, or with other known hepaticdiseases such as hepatic failure, hepatic cirrhosis, portal hypertension (withesophageal varices), active hepatitis, etc.;

11. Patients with a heart function rating above Class II (according to the New YorkHeart Association (NYHA) heart function rating) or a history of congestive heartfailure;

12. Patients with malignant tumors or undergoing anti-tumor therapy;

13. Allergic to experimental drugs or similar ingredients or materials used in imagingexaminations;

14. Patients during pregnancy, lactation or planning pregnancy;

15. Patients who have a history of epilepsy or have had seizure-like symptoms at theonset of stroke, or suffer from serious mental disorders, intellectual disabilitiesor dementia;

16. Alcohol dependence, or drinking more than 3 units (male) or 2 units (female) ofalcohol within 24 hours prior to onset (1 unit =360 mL beer or 45 mL liquor with 40%alcohol or 150 mL wine);

17. Patients have participated in other drug or non-drug clinical studies, or areparticipating in another clinical study within 3 months before signing informedconsent form;

18. Patients have a history of severe head trauma or stroke within the past 3 months;

19. Patients are suffering from severe systemic diseases, with a life expectancy of lessthan 90 days;

20. Patients who are judged unsuitable for participation by the investigators in thestudy.