Argatroban Plus R-tPA for Acute Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Therefore, all guidelines recommend intravenous thrombolysis as the first treatment of ischemic stroke patients within 4.5 hours of onset. However, about 1/3 patients receiving thrombolysis will have good prognosis, while a large number of patients will still be disabled and even dead. How to improve the neurological prognosis of thrombolytic patients has been a hot topic in the world. Recent studies have found that the combined application of argatroban and rt-PA in the treatment of AIS might improve the clinical prognosis and not significantly increase bleeding. Some studies have reported that the combined application of argatroban and rt-PA could improve the blood vessel opening rate, and prevent re-occlusion after opening. Based on the discussion, the present study is designed to explore the efficacy and safety of argatroban plus rt-PA in the treatment of AIS.

Official Title
-----------------
Argatroban Plus R-tPA for Acute Ischemic Stroke: a Prospective, Random, Open Label, Blinded Assessment of Outcome Multi-center Study

Conditions
-----------------
Stroke

Intervention / Treatment
-----------------
* Drug: rt-PA
* Drug: Argatroban


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-80 years old; Time from onset to treatment ≤4.5 hours; NIHSS ≥ 6 Diagnosis of ischemic stroke Signed informed consent by patient self or legally authorized representatives. Exclusion Criteria: mRS≥2; History of stroke within 3 months; History of intracranial hemorrhage; Suspected subarachnoid hemorrhage; Intracranial tumour, vascular malformation or arterial aneurysm; Major surgery within 1 month; Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg; Platelet count < 105/mm3; Heparin therapy or oral anticoagulation therapy within 48 hours; Abnormal APTT; Thrombin or Xa factor inhibitor; Severe disease with a life expectancy of less than 3 months; Blood glucose < 50 mg/dL (2.7mmol/L); Patients who have received any other investigational drug or device within 3 months; Pregnancy; Researchers consider patients inappropriate to participate in the registry.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Argatroban combined with rt-PA<br>Drug: Argatroban combined with rt-PA Argatroban as a 100 ug/kg bolus over 3 to 5 minutes was administered intravenously within 1 hour of the tPA bolus followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%) | Drug: rt-PA<br>* Intravenous throbolysis with 0.9mg/kg rtPA<br>Drug: Argatroban<br>* 100 ug/kg bolus over 3 to 5 minutes was administered intravenously, followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%)<br>|
| Active Comparator: rt-PA<br>Drug: rt-PA Intravenous throbolysis with 0.9mg/kg rtPA. | Drug: rt-PA<br>* Intravenous throbolysis with 0.9mg/kg rtPA<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of mRS (0-1） |  | 90±7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of mRS (0-2） |  | 90±7 days | 
| proportion of more than 2 decrease in NIHSS score | NIHSS, National Institute of Health stroke scale | 48 hours | 
| proportion of early neurological deterioration | Early neurological deterioration, defined as more than 4 increase in National Institute of Health stroke scale score | 48 hours | 
| Vascular Events | The occurence of stroke or other vascular events | 90±7 days | 
| symptomatic intracranial hemorrhage |  | 48 hours |