Intra-arterial Tenecteplase During First Thrombectomy Attempt for Acute Stroke (BRETIS-TNK II)

Study Overview
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Brief Summary
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A recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). The study aimed to determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients.

Official Title
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Intra-arterial Tenecteplase During First Thrombectomy Attempt for Acute Stroke (BRETIS-TNK II): a Prospective, Randomized, Adaptive Enrichment, Open-label, Blinded End Point, 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 years; Stroke patient with large vessel occlusion (internal carotid artery, M1 or M2 of middle cerebral artery, basilar artery, or intracranial segment of vertebral artery) who meets criteria for endovascular treatment within 24 hours of stroke onset; The modified Rankin Scale (mRS) score before onset ≤ 2; ASPECTS 6 or greater on CT Signed informed consent. Exclusion Criteria: hemorrhagic stroke; Tandem occlusion; Coagulation disorders, systematic hemorrhagic tendency, thrombocytopenia (<100000/mm3); Severe hepatic or renal dysfunction, increase in ALT or AST (more than 2 times of upper limit of normal value), elevated serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis; Severe uncontrolled hypertension (systolic blood pressure over 200mmHg or diastolic blood pressure over 110 mmHg); Patients with contraindication or allergic to any ingredient of drugs in our study; Pregnancy, or plan to get pregnant or during active lactation; Suspected septic embolus or infective endocarditis The estimated life expectancy is less than 6 months due to other serious diseases; Other conditions unsuitable for this clinical study as assessed 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: TNK group<br> | Drug: Tenecteplase<br>* intra-arterial tenecteplase during endovascular treatment<br>|
| No Intervention: control group<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of favorable outcome | Favorable outcome is defined as modified Rankin Scale (mRS) score of 0-2 | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of excellent outcome | Excellent outcome is defined as modified Rankin Scale (mRS) score of 0-1 | Day 90 | 
| proportion of successful reperfusion after the first-pass or final pass of endovascular treatment | Successful reperfusion is defined as defined as modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3 | immediately after the first-pass or final pass of endovascular treatment | 
| Distribution of modified Rankin Scale (mRS) | mRS scores range from 0 to 6:0, no symptoms, 1 = symptoms without clinically significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability; and 6 = death. | Day 90 | 
| Change in cerebral circulation time after intervention |  | immediately after endovascular treatment | 
| occurrence rate of early neurological improvement | early neurological improvement was defined as a 4 point or greater decrease in NIHSS | 24 (-6/+24) hours | 
| change in National Institute of Health stroke scale (NIHSS) | NIHSS scores range 0-42, with higher scores indicating greater stroke severity | 24 (-6/+24) hours | 
| occurrence rate of the composite events of nonfatal stroke, nonfatal myocardial infarction, and other cardiovascular events |  | Day 90 | 
| occurrence rate of symptomatic intracranial hemorrhage | symptomatic intracranial hemorrhage is defined as an increase in the NIHSS score of ≥4 points as a result of the intracranial hemorrhage. | 24 (-6/+24) hours | 
| occurrence rate of parenchymal hemorrhage | parenchymal hemorrhage was defined as confluent bleeding occupying and causing mass effect | 24 (-6/+24) hours | 
| percentage of severe adverse events |  | 24 (-6/+24) hours | 
| cerebral edema | cerebral edema was measured as the amount of midline shift of the brain on neuroimaging | 24 (-6/+24) hours | 
| death due to all causes |  | Day 7 or during hospitalization | 
| occurrence rate of the distal emboli after first pass | The emboli means occlusion of the distal artery determined by DSA. | immediately after first pass | 
| occurrence rate of extracranial hemorrhage | extracranial hemorrhage means other bleeding events except intracranial hemorrhage | 24 (-6/+24) hours |