This trial will enroll patients that have been diagnosed with minor stroke, which has occurred within the past 6 hours. TRUST is a prospective multicenter, randomized, blinded-endpoint study to evaluate the efficacy and safety of Urokinase Thrombolysis for patients with minor stroke.

China is currently faced with the heaviest stroke burden due to the tremendous population and susceptibility to cerebrovascular disease. As has been assessed, deaths caused by cerebrovascular disease are three times of cardiovascular disease. Within whole population with cerebrovascular disease, minor stoke have taken a significant part of the disease burden. Thus the population with minor stoke is one of the most important parts in efficient prevention of cerebrovascular disease. According to phase I and II data from national stoke registration in China, 35.25% to 42.23% cases were minor ischemic strokes. However, in clinical practice, the minor ischemic stroke patients are likely to be ignored and some might have poor prognosis. As has been demonstrated by a number of studies, up to one third of the acute non-disabling ischemic stroke without in-time thrombolysis may suffer from disabling or death at 90-day follow-up.

Several studies have demonstrated the potential benefits of thrombolysis compared usually with placebo, including the Third International Stroke Trail ( IST-3, rt-PA to placebo, patients within 3 hours after attack, with blood pressure lower than 185/110mmHg and NIHSS≤5)，National Institute of Neurological Disorders and Stroke rt-PA Stroke Study（ NINDS, rt-PA to placebo, patients with mild ischemic stroke recognized by 5 different definitions）.

Urokinase is a kind of non-selective plasminogen activator, urokinase acted as effective catalyzer in the transferring of both free and protein-binding plasminogen to plasmin, thus inducing thrombolysis. As one of the widely used medication for intravenous thrombolysis in China, urokinase has been suggested the the efficacy and safety for ischemic stroke. With easier availability and lower price, urokinase has provided a promising alternation to patients who need thrombolysis in China, especially in less developed areas. The Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018 has recommended urokinase as an alternation in the treatment of acute ischemic stroke within 6-hour time window as well, if rt-PA is not available or affordable. However, randomized and multicenter clinical trial of urokinase thrombolysis for minor stroke is still vacant, which couldn't provide more persuasive evidence.

TRUST is a prospective multicenter, randomized, single-blind evaluation study to evaluate the efficacy and safety of Urokinase Thrombolysis for patients with minor stroke. The trail will enroll a total of 1002 minor stroke patients within a 6 hour time window with a NIHSS score ≤5 at the time of randomization. Randomization will be 1:1 to Urokinase Thrombolysis (experimental) or Antiplatelet agents (control). Patients will receive 1 million units urokinase dissolved by 100ml saline through intravenous infusion within 30min or oral antiplatelet agents. All patients will undergo CT or MRI before treatment and will undergo the second CT within 36 hours after treatment. Patients will be followed up at 36h, 7d and 90 days. The primary outcome measures including the proportion of patients with a modified Rankin Scale(mRS) of 0 or 1 at 90-day follow-up and the patients with symptomatic intracranial hemorrhage within 36 hours. Secondary outcome measures cover new vascular events, the Progress of MRS score, Neurological impairment, Daily function evaluations, Quality of life assessments, Overall mortality and Adverse events and severe adverse events within 90 days.

Inclusion Criteria:

1. Adult patients: 18-80 years old
2. The time from last seen well to treatment < 6 hours
3. Minor stroke defined as a baseline NIHSS ≤5 at the time of randomization..
4. First onset or pre-stroke mRS≤1
5. Informed consent signed

Exclusion Criteria:

1.Hyperdensity on CT suggesting intracranial hemorrhage

2.Large acute stroke >1/3 middle cerebral artery (MCA) territory visible on CT or MRI

3.Other contraindications of intravenous thrombolysis, including but not limited to:

1. Intracranial tumor, arteriovenous malformation
2. Coma or confirmed as severe stroke by clinical assessment (e.g. NIHSS ≥25) or proper imaging methods
3. With seizure
4. Stroke attack within past three months
5. Heparin administration within 48h before onset, with APTT longer than upper limit
6. Stroke history with diabetes
7. Platelet count ≤100×10^9/L
8. Difficult to control hypertension, defined by systolic pressure ≥185mmHg or diastolic pressure ≥110 mmHg in 3 tests with at least ten minutes interval, under well guided medications.
9. Blood glucose <50mg/dl（2.7mmol/l）or >400mg/dl（22.2mmol/l）
10. Obvious hemorrhage within past 6 months
11. Oral anti-coagulation drug administration (e.g. warfarin) with INR>1.5
12. Intracranial hemorrhage or suspected intracranial hemorrhage (including subarachnoid hemorrhage)
13. Pregnancy or lactation.
14. History of severe CNS damage (e.g. tumor, arterial aneurysm or CNS surgery)
15. Hemorrhagic retinopathy, e.g. diabetes (hemorrhages suggested by optic impairment) or other hemorrhagic ocular lesions.
16. Bacterial endocarditis or pericarditis.
17. Prolonged or traumatic CPR (>2min), puncture in nonstress vessels within past 10 days, such as subclavian vein puncture.
18. Acute pancreatitis.
19. Confirmed ulcerative gastric or intestinal problems within 3 months.
20. Arterial aneurysm or arteriovenous malformation.
21. Any tumor that increase risk of hemorrhage.
22. Severe hepatic diseases, like hepatic failure, liver cirrhosis, portal hypertension, esophageal varices or active hepatitis.
23. Major surgery, severe trauma or craniocerebral trauma within past 10 days.
24. Allergy to any components of urokinase.

4.Severe, fatal diseases with less than 3 month expected survival.

5.Intended to receive standard rt-PA thrombolysis or intravascular therapy.

6.Already participating in other studies that conflict to this study.

7.Unable to accomplish the follow-up.