Improving Neurological Outcome for Acute Basilar Artery Occlusion With Sufficient Recanalization After Thrombectomy by Intraarterial Tenecteplase (INSIST-IT)

Study Overview
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Brief Summary
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The potential benefit of intraarterial tenecteplase in acute basilar artery occlusion (BAO) patients with successful reperfusion following endovascular treatment (EVT) has not been studied. The current study aimed to explore the efficacy and safety of intraarterial tenecteplase in acute BAO patients with successful reperfusion after EVT.

Official Title
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Improving Neurological Outcome for Acute Basilar Artery Occlusion With Sufficient Recanalization After Thrombectomy by Intraarterial Tenecteplase (INSIST-IT): a Prospective, Randomized, Open-label, Blinded-end Point, Multicenter Trial

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 Patients with basilar artery occlusion who received endovascular treatment within 24 hours of estimated time of stroke onset as per BASICS trial definition; National Institute of Health Stroke Scale (NIHSS) ≥ 6 before endovascular treatment; Successful recanalization (mTICI 2b-3) after endovascular treatment; PC-ASPECTS ≥ 6 on CT; Absence of parenchymal hematoma on CT images done in the angio suite immediately after the procedure; Modified Rankin Scale score before stroke onset ≤ 3; Signed informed consent by patient or their legally authorized representative. Exclusion Criteria: baseline PC ASPECTS < 5 on CT; More than six retrieval attempts in the same vessel; Hemorrhagic stroke: cerebral hemorrhage, subarachnoid hemorrhage; Coagulation disorders, systemic hemorrhagic diathesis, thrombocytopenia (<100000/mm3), or INR > 1.7; Severe hepatic or renal dysfunction, increase in ALT or AST (more than 2 times of upper limit of normal value), increase in serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis; After recanalization, severe and sustained (i.e., > 5 minutes) uncontrolled hypertension (systolic blood pressure over 180mmHg or diastolic blood pressure over 105 mmHg) refractory to antihypertensive medication; Patients with contraindication or allergic to any ingredient of drugs in our study Pregnancy, plan to get pregnant or during lactation The estimated life expectancy is less than 6 months due to other serious diseases; Other conditions unsuitable for this clinical study 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<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 functional outcome | favorable functional outcome is defined as a modified Rankin Scale (mRS) score of 0 to 3 | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with an improved modified thrombolysis in cerebral infarction score |  | immediately after intraarterial TNK administration or at the end of endovascular treatment | 
| the proportion of patients with modified Rankin Score (mRS) 0 to 1 | 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 | 
| the proportion of patients with modified Rankin Score (mRS) 0 to 2 | 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 | 
| ordinal distribution of modified Rankin Score (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 modified Rankin Score (mRS) compared with premorbid 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 National Institute of Health stroke scale (NIHSS) | NIHSS scores range from 0 to 42, with higher scores indicating more severe neurological deficit | 24 (-6/+24) hours | 
| proportion of early neurological improvement | early neurological improvement is defined as a NIHSS decrease ≥4 | 24 (-6/+24) hours | 
| change in the cerebral circulation time |  | immediately after tenecteplase | 
| the occurrence rate of composite events of recurrent stroke, cardiovascular or cerebrovascular events |  | Day 90 | 
| proportion of sympomatic intracranial hemorrhage | sympomatic intracranial hemorrhage is defined as a NIHSS increase ≥4 caused by intracranial hemorrhage | 24 (-6/+24) hours | 
| proportion of intraparenchymal hemorrhage | intraparenchymal hemorrhage was defined as confluent bleeding occupying and causing mass effect | 24 (-6/+24) hours | 
| the percentage of severe adverse events |  | 24 (-6/+24) hours | 
| cerebral edema | cerebral edema was measure by the mount of midline shift of the brain on neuroimaging | 24 (-6/+24) hours | 
| all-cause mortality |  | 10 days | 
| the number of tenecteplase infusions interrupted due to suspected active bleeding |  | during endovascular treatment (up to 2 hours) |