The primary purpose of this trial is to compare the efficacy of different doses of investigator product and comparator product in patients with acute ischemic stroke in 4.5 Hours after stroke onset, and provide a basis of drug administration for phase Ⅲ clinical trial. The secondary purpose of this trial is to compare the safety of different dose of investigational product and comparator product in patients with acute ischemic stroke in 4.5 hours afterstroke onset .
This study is a multicenter, prospective randomised, open blinded endpoint study. Patients with acute ischemic stroke need to undergo CT or MRI to exclude intracranial hemorrhage and perform NIHSS score before enrollment. Subjects who have passed the screening criteria according to the inclusion and exclusion criteria will be randomly assigned to low-dose test drugs, high-dose test drugs or reference drugs for thrombolytic therapy at a ratio of 1:1:1. The random stratification factor is the thrombolysis time window ("≤3h" vs "3\~4.5h"). The start of administration of the study drug is recorded as 0h, CT or MRI and NIHSS score, laboratory test, and electrocardiogram were performed at 24 hours; NIHSS score was performed at 72 hours; NIHSS score,laboratory test and electrocardiogram were performed on the14th day(the start of administration is recorded as Day 1 ,then the 14th day after administration should be recorded as Day 15 ); mRS score and Barthel index score were performed on the 30th day (Day 31); mRS score and Barthel index score were performed on the 90th day (Day 91).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
180
Drug: r-PA Dose: stick 18 mg; Mode of admin: The high-dose group (18 mg + 18 mg) was divided into two intravenous injections. the first intravenous bolus injection of 18mg,after 30mins, the second intravenous bolus injection of 18 mg, Push slowly for more than 2mins each time.
Drug: r-PA Dose: stick 18 mg; Mode of admin: The low-dose group (12 mg + 12 mg) was divided into two intravenous injections, the first intravenous bolus injection of 12 mg, after 30mins, the second intravenous bolus injection of 12 mg, Push slowly for more than 2mins each time.
Drug: Alteplase for Injection Dose:50mg; 20mg Mode of admin: 0.9 mg/kg (maximum dose of 90 mg) intravenous, 10% of which was injected intravenously within the first 1min, and the rest continued intravenous infusion for 1 h.
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
The proportion of subjects with NIHSS score ≤1 or the decrease of 4 points or more from the baseline on the 14th day after treatment;
The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).
Time frame: on the 14th day after treatment
The proportion of subjects with NIHSS score ≤1 or the decrease of 4 points or more from the baseline at 72 hours after treatment;
Proportion of patients with ≥4 point reduction in NIHSS or reaching 0-1 at 3 days (favourable clinical response) adjusted for baseline NIHSS and age.
Time frame: at 72 hours after treatment;
The proportion of subjects with mRS score of 0-1 on the 30th day and 90th day after treatment;
The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0-5. A separate category of 6 is usually added for patients who expire. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge. The scale runs from 0-5, running from perfect health without symptoms to Severe disability 0. -No symptoms. 1\. -No significant disability. Able to carry out all usual activities, despite some symptoms. 2 .-Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3\. -Moderate disability. Requires some help, but able to walk unassisted. 4\. -Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5\. -Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
Time frame: on the 30th day and 90th day after treatment;
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The proportion of subjects with mRS score of 0-2 on the 30th day and 90th day after treatment;
Time frame: on the 30th day and 90th day after treatment;
Continuous changes of mRS scores on the 30th and 90th days after treatment;
Time frame: on the 30th and 90th days after treatment;
The proportion of subjects with Barthel index score≥95 on the 30th day and 90th day after treatment;
The Barthel Index of Activities of Daily Living (ADLs) measures functional disability by quantifying patient performance in 10 activities of daily life. These activities can be grouped according to self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers, and stair climbing). 5-point increments are used in scoring, with a maximal score of 100 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state.
Time frame: on the 30th day and 90th day after treatment;