ALteplase in Patients With LOW NIHSS and Specified Disabling Deficits

Study Overview
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Brief Summary
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About 1/3 patients with mild stroke have poor prognosis, whether patients with this type undergo thrombolysis has been a controversial issue. A pooled analysis published in the Lancet in 2014 included 9 high-quality RCT studies of intravenous thrombolysis such as NINDS and IST3, and a total of 666 (10%) patients with mild stroke were included in the analysis. For mild stroke, the proportion of good prognosis in the control group and the alteplase group was 58.9% and 68.7% (OR 1.48, 95%Cl 1.07-2.06), respectively. Therefore, guidelines recommended alteplase thrombolytic therapy for patients with mild stroke. However, PRISMS, a randomized controlled trial of intravenous thrombolytic therapy for mild stroke published in 2018, found that alteplase intravenous thrombolytic therapy did not improve clinical outcomes compared with aspirin in patients with mild non-disabled stroke (90-day mRS 0-1 ratio 78.2% vs 81.5%), and the incidence of symptomatic intracranial hemorrhage was higher. However, a major limitation of the PRISMS study was that more than 85% of patients had numbness and dysarticulation, so this conclusion cannot be extrapolated to patients with other mild stroke symptoms. Moreover, due to the early termination of the sponsorship of this trial, the number of enrolled cases did not reach the pre-designed number, resulting in a serious decline in the authenticity of the study results. Symptoms and outcomes of minor stroke are important criteria for assessment. However, there is currently no uniform standard for the assessment of disability. Therefore, the center developed a mild stroke EMSS assessment scale to refine the disability assessment of stroke symptoms. It was found that intravenous thrombolytic therapy was safe and effective for patients with symptoms such as dizziness, disorientation, memory impairment, decreased muscle strength at the proximal end of one limb, and ataxia while standing. Therefore, the purpose of this study was to investigate whether ischemic stroke patients with onset or detection time within 4.5 hours, and mild stroke patients with NIHSS score ≤5 with any of the following symptoms: dizziness, disorientation, memory impairment, single proximal muscle strength decline, or ataxia while standing could benefit from intravenous thrombolysis based on CT/MRI screening in the Chinese population.

Official Title
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ALteplase for the Treatment of Acute Ischemic Stroke in Patients With LOW National Institutes of Health Stroke Scale and Specified Disabling Deficits

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: Alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of onset ≥18 years; Patients with acute cerebral infarction or transient ischemic attack within 4.5 hours of onset; NIHSS≤5, and EMSS score ≥2 combined with any of the following conditions A. Dizziness B. Whole brain - orientation D. Speech E. Upper/lower limb muscle strength F. Ataxia - Standing Exclusion Criteria: pre-disease mRS≥2; Obvious history of head trauma or stroke in the past 3 months; Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extrinsic hematoma); Previous history of intracranial hemorrhage; Intracranial tumors and giant intracranial aneurysms; Had intracranial or intraspinal surgery in the past 3 months; Arterial puncture in the incompressible area within the last 1 week; Gastrointestinal or urinary tract bleeding within the past 21 days; Major surgical operations within the last 2 weeks; Uncontrolled severe hypertension (systolic blood pressure ≥180mmHg or diastolic blood pressure ≥100mmHg after medication); Blood sugar <2.8mmol/L or > 22.22mmol/L; Have received heparin therapy or oral anticoagulant therapy within 48 hours; Platelet count <100,000/mm3 (if clinical abnormality is not suspected, validation before randomization is not required); Taking oral warfarin with INR>1.6; PT > 15s; Pregnancy; Allergic to the experimental drug; Diagnosed Alzheimer's disease, frontotemporal dementia, schizophrenia Patients deemed unsuitable for participation in this trial by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombolysis group<br>intravenous alteplase (0.9 mg/kg; maximum dose, 90mg; 10% administered as a 1-minute bolus, the remaining infused over 1 hour; | Drug: Alteplase<br>* intravenous alteplase(0.9 mg/kg;maximum dose, 90mg; 10% administered as a 1-minute bolus,the remaining infused over 1 hour)<br>|
| No Intervention: Control group<br>according to guideline | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| excellent functional outcome at 90 days, defined as a score of 0 to 1 on the mRS for the evaluation of neurologic disability | defined as a score of 0 to 1 on the mRS for the evaluation of neurologic disability | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of mRS Score 0-2 | defined as a score of 0 to 2 on the mRS for the evaluation of neurologic disability | 90 days | 
| Early neurological function improved at 7 days, and NIHSS score decreased by ≥2 points compared with baseline | defined as NIHSS score decreased by ≥2 points compared with baseline | 7 days | 
| Early neurological deterioration caused by non-intracranial hemorrhage at 7 days: NIHSS score increased by ≥2 points | defined as NIHSS score increased by ≥2 points compared with baseline | 7 days | 
| Cognitive function assessment | Hopkins Verbal Learning Test-Revised [HVLT-R] trials 1, 2, and 3; digit symbol coding from the Wechsler Adult Intelligence Scale III [WAIS III]; Forward and Backward Digit Span test; Benton Judgment of Line Orientation test, form V; HVLT-R trial 4 and recognition; semantic fluency [Animal Naming test]; Boston Naming Test [BNT; 15-item short form]) at 6-month | 6 months | 
| Cognitive function assessment | Hopkins Verbal Learning Test-Revised [HVLT-R] trials 1, 2, and 3; digit symbol coding from the Wechsler Adult Intelligence Scale III [WAIS III]; Forward and Backward Digit Span test; Benton Judgment of Line Orientation test, form V; HVLT-R trial 4 and recognition; semantic fluency [Animal Naming test]; Boston Naming Test [BNT; 15-item short form]) at 1-year | 1 year | 
| Changes in functional brain connectivity | Changes in functional brain connectivity by function MRI | 6 months | 
| Barthel Index | Barthel Index | 3 months |