Tenecteplase Plus Butylphthalide for Acute Ischemic Stroke Within 4.5 to 6 Hours of Onset (EXIT-BT2)

Study Overview
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Brief Summary
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To date, the benefit of intravenous thrombolysis is confined within 4.5 hours of onset for acute ischemic stroke (AIS) patients without advanced neuroimaging selection. Unpublished pilot EXIT-BT (EXtending the tIme window of Thrombolysis by ButylphThalide up to 6 Hours after onset) suggest the safety, feasibility and potential benefit of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 hours of onset. The current study aims to investigate the efficacy and safety of TNK plus NBP for AIS within 4.5 to 6 hours of onset.

Official Title
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Tenecteplase Plus Butylphthalide for Acute Ischemic Stroke Within 4.5 to 6 Hours of Onset (EXIT-BT2): a Prospective, Randomized, Open Label, Blinded Endpoint, and Multi-center Study

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: Tenecteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 year Acute ischemic stroke confirmed by non-contrast computed tomography; The time from last known well to treatment: 4.5 - 6 hours; NIHSS ≥ 4 at randomization; First stroke onset or past stroke without obvious neurological deficit (mRS≤2); Signed informed consent. Exclusion Criteria: Pre-stroke disability (mRS≥3); Planned intravenous thrombolysis based on WAKE-UP or EXTEND study criterion; Any contraindication to intravenous thrombolysis: Obvious head injury or stroke within 3 months; Subarachnoid or intracranial hemorrhage; History of intracranial hemorrhage; Intracranial tumor, arteriovenous malformation or aneurysm; Intracranial or spinal cord surgery within 3 months; Myocardial infarction within 3 months; Major surgery within 1 month; Gastrointestinal or urinary tract hemorrhage within the previous 30 days; Arterial puncture at a noncompressible site within the previous seven days; Active internal hemorrhage; Coagulation abnormalities: platelet count of <100000/mm3; Aortic arch dissection; Heparin therapy within 24 hours; Infective endocarditis; Oral warfarin is being taken and INR>1.6 or APTT abnormal; Systolic pressure ≥185 mmHg or diastolic pressure ≥110 mmHg; Blood glucose < 50 mg/dl (2.7mmol/L); Neurological deficit after epileptic seizures; Pregnancy; Allergy to test drugs; Comorbidity with other serious diseases; Participating in other clinical trials within 3 months; Patients not suitable for the study considered by researcher.

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: Tenecteplase group<br>intravenous thrombolysis with tenecteplase, combined with butylphthalide. | Drug: Tenecteplase<br>* intravenous butylphthalide (NBP) (25mg, 100 mL sodium chloride injection) and tenecteplase (0.25 mg/kg, a single bolus over 5 to 10 seconds, a maximum of 25 mg), followed by intravenous NBP (25mg, 100 mL sodium chloride injection, two times daily for 10±2 days). This will be later followed by oral soft NBP capsules (0.2 g, three times daily for the next 80±2 days)<br>|
| Other: Control group<br>standard stroke care based on national guideline | Drug: Tenecteplase<br>* intravenous butylphthalide (NBP) (25mg, 100 mL sodium chloride injection) and tenecteplase (0.25 mg/kg, a single bolus over 5 to 10 seconds, a maximum of 25 mg), followed by intravenous NBP (25mg, 100 mL sodium chloride injection, two times daily for 10±2 days). This will be later followed by oral soft NBP capsules (0.2 g, three times daily for the next 80±2 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of modified Rankin Scale (mRS) 0-1 | The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome | 90±7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of modified Rankin Scale (mRS) 0-2 | The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome | 90±7 days | 
| ordinal distribution of modified Rankin Scale (mRS) | The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome | 90±7 days | 
| change in National Institute of Health stroke scale (NIHSS) score | the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome. | 24 (-6/+12) hours | 
| change in National Institute of Health stroke scale (NIHSS) score | the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome. | 10±2 days | 
| occurrence of early neurological improvement (ENI) | ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score | 24 (-6/+12) hours | 
| new stroke or other vascular event(s) |  | 90±7 days | 
| all-cause mortality |  | 90±7 days | 
| symptomatic intracranial hemorrhage | any evidence of bleeding on the head CT scan associated with clinically significant neurological deterioration (NIHSS score ≥4 points increase) | 24 (-6/+12) hours | 
| intracranial hemorrhage | any evidence of bleeding on the head CT scan, classified by the Heidelberg Bleeding Classification | 24 (-6/+12) hours | 
| major systemic bleeding event |  | 24 (-6/+12) hours | 
| any bleeding event |  | 24 (-6/+12) hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombolysis