Rescue Thrombolysis for Medium Vessel Occlusion (RESCUE-TNK)

Study Overview
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Brief Summary
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The best reperfusion strategy for medium-sized vessel occlusion (MeVO) is not well established. Given the proven treatment effect of intra-arterial thrombolysis in patients with large vessel occlusion (LVO), the investigators hypothesized that intra-arterial tenecteplase (TNK) could increase the recanalization rate of MeVO and thus improve clinical outcome. The current study aimed to explore the safety and efficacy of intra-arterial TNK in patients with MeVO.

Official Title
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Rescue Thrombolysis for Medium Vessel Occlusion (RESCUE-TNK): a Prospective, Randomized, Open-label, Blinded End Point, and 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 years; Medium vessel occlusion (MeVO), referring to M2-3 of MCA; A1-3 of ACA; P1-3 of PCA; PICA, AICA or SCA (including primary, distal embolism in the same region after thrombectomy or concurrent embolism in other regions). Primary MeVO as detected by the first DSA examination or secondary MeVO after mechanical thrombectomy for large vessel occlusion; MeVO causes neurological deficits in motor strength, language, vision etc; Endovascular mechanical thrombectomy cannot be performed as assessed by the investigator; Absence of parenchymal hematoma on CT images performed in the angio suite. Within 24 hours from symptom onset; Signed informed consent by patient or patient's legally authorized representative. Exclusion Criteria: Patients with completed infarction in the territory of the MeVO on non-contrast CT; Patients with intracranial hemorrhage; Coagulation disorders, tendency for systemic hemorrhagic, thrombocytopenia (<100,000/mm3); 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 mechanical thrombectomy, severe and sustained (> 5 minutes) uncontrolled hypertension (systolic blood pressure over 180mmHg or diastolic blood pressure over 105 mmHg); Patients with contraindication or allergy to any ingredient of study medication; Pregnancy, plan to get pregnant or active lactation; 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<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 patients with successful Medium vessel occlusion (MeVO) recanalization | successful MeVO recanalization is defined as the expanded treatment in cerebral ischemia (eTICI) score 2b67-3 in the territory of the target occluded MeVO artery | immediately after finishing intra-arterial tenecteplase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of modified Rankin Scale (mRS) 0-1 | mRS scores range from 0 to 6, with higher scores indicating worse outcome | Day 90 | 
| proportion of modified Rankin Scale (mRS) 0-2 | mRS scores range from 0 to 6, with higher scores indicating worse outcome | Day 90 | 
| distribution of modified Rankin Scale (mRS) | mRS scores range from 0 to 6, with higher scores indicating worse outcome | Day 90 | 
| incidence of early neurological improvement | early neurological improvement is defined as a decrease of more than 4 points or reaching 0 points in NIHSS score, compared with baseline | 24 (-6/+24) hours | 
| Changes in National Institute of Health stroke scale (NIHSS) | NIHSS scores range 0-42, with higher scores indicating greater stroke severity | 24 (-6/+24) hours | 
| rate of visual recovery in patients with posterior cerebral artery occlusion |  | 7 days or at hospital discharge | 
| proportion 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 | 
| proportion of parenchymal hematoma type 1 and 2 |  | 24 (-6/+24) hours | 
| all serious adverse events |  | 24 (-6/+24) hours | 
| all-cause death |  | 7 days | 
| recurrent stroke, cardiovascular events, other vascular events and death |  | 90 days |