EXtending the tIme Window of Thrombolysis by ButyphThalide up to 6 Hours After Onset (EXIT-BT)

Study Overview
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Brief Summary
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To date, the time window of intravenous thrombolysis is limited within 4.5 hours of stroke onset. Although EXTEND study has proved that intravenous thrombolysis can be extended from 4.5 to 9 hours, but the eligible patients must be selected by CTP. Thus, it is of clinical importance how to extend the time window of intravenous thrombolysis, which can benifit more patients. The current trial aims to investigate the effect of intravenous thrombolysis with TNK from 4.5 to 6 hours in ischemic stroke with help of Butyphthalide, which was found to be neuroprotective.

Official Title
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EXtending the tIme Window of Thrombolysis by ButyphThalide up to 6 Hours After Onset (EXIT-BT): a Prospective, Randomized, Blinded Assessment of Outcome and Open Label Multi-center Study

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: TNK-Tissue Plasminogen Activator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age: 18-80; ischemic stroke confirmed by brain CT or MRI the time from onset to treatment: 4.5-6 hours NIHSS≥4 prestroke mRS≤1 signed informed consent Exclusion Criteria: prestroke mRS≥2 planned endovascular treatment planned intravenous thrombolysis based on WAKE-UP or EXTEND study criterion any contraindiction of intravenous thrombolysis other unsuitable conditions judged by investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: TNK group<br>intravenous thrombolysis with 0.25 mg/kg TNK, with the biggest dose of 25 mg | Drug: TNK-Tissue Plasminogen Activator<br>* 0.25 mg TNK thrombolysis<br>|
| Placebo Comparator: control group<br> | Drug: TNK-Tissue Plasminogen Activator<br>* 0.25 mg TNK thrombolysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| symptomatic intracerebral hemorrhage | any evidence of bleeding on the head CT scan associated with clinically significant neurological deterioration (NIHSS score ≥4 points increase) | 36 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of excellent prognosis (mRS 0-1) | the minimum and maximum values of modified Rankin Score are 0 and 6, respectively; higher score mean a worse outcome | Day 90 | 
| The proportion of favourable prognosis (mRS 0-2) | the minimum and maximum values of modified Rankin Score are 0 and 6, respectively; higher score mean a worse outcome | Day 90 | 
| Distribution of modified Rankin Score | the minimum and maximum values of modified Rankin Score are 0 and 6, respectively; higher score mean a worse outcome | Day 90 | 
| Changes in National Institute of Health stroke scale (NIHSS) | the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome | 24 hours, 2 weeks | 
| any intracerebral hemorrhage | the evidence of bleeding on the head CT scan | 36 hours | 
| any cerebral microbleeding(CMB) | CMB is measured by SWI sequence | 48 hours | 
| infarct volume | infarct volume is measured by DWI sequence | 48 hours | 
| proportion of death | death due to any cause | Day 90 |