Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke

Study Overview
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Brief Summary
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The purpose of this trial is to investigate whether intravenous rhTNK-tPA prior to endovascular treatment can improve 90-day functional outcome of stroke patients with large vessel occlusion who are thrombolysis-eligible within 4.5 hours of symptom onset.

Detailed Description
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The DEVT, SKIP and DIRECT-MT trials showed that endovascular treatment alone is not inferior to intravenous alteplase bridging with endovascular treatment in terms of achieving 90-day functional independence for stroke patients with large vessel occlusion. The EXTEND-IA TNK part 1 and part 2 demonstrated that intravenous thrombolysis with tenecteplase is superior to alteplase before endovascular treatment. However, it is unclear whether intravenous tenecteplase bridging with endovascular treatment is superior to endovascular treatment alone. The purpose of this trial is to investigate whether intravenous rhTNK-tPA bridging with endovascular treatment is better than endovascular treatment alone for stroke patients with large vessel occlusion who are thrombolysis-eligible within 4.5 hours of onset.

Official Title
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Intravenous rhTNK-tPA Bridging With Endovascular Treatment Versus Endovascular Treatment Alone For Stroke Patient With Large Vessel Occlusion: A Multicenter, Randomized Controlled Trial

Conditions
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Stroke, Acute, Stroke, Ischemic

Intervention / Treatment
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* Drug: rhTNK-tPA
* Other: Endovascular treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older; Acute ischemic stroke confirmed by clinical symptoms or imaging examination; MCA-M1 or -M2, basilar artery, or posterior cerebral artery-P1 occlusion proved by CTA/MRA; Eligible for intravenous thrombolysis with TNK-tPA; Time from stroke onset to randomization within 4.25 hours; Written informed consent is obtained from patients and/or their legal representatives. Exclusion Criteria: CT or MR evidence of intracranial hemorrhage; Contraindications of intravenous thrombolysis; Currently in pregnant or lactating or serum beta HCG test is positive on admission; Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys; Current participation in another clinical trial Arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel; Patients with a preexisting neurological or psychiatric disease that would confound the neurological functional evaluations; Patients with occlusions in multiple vascular territories (e.g. bilateral anterior circulation, or anterior/posterior circulation); CT or MR evidence of mass effect or intracranial tumor (except small meningioma); CT or MR angiography evidence of intracranial arteriovenous malformations or aneurysms; Any terminal illness with life expectancy less than 6 months; Unlikely to be available for 90-day follow-up.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conbined treatment group<br>intravenous tenecteplase bridging with endovascular treatment | Drug: rhTNK-tPA<br>* intravenous thrombolysis with rhTNK-tPA followed by endovascular treatment<br>* Other names: TNK-tPA;Other: Endovascular treatment<br>* endovascular treatment<br>* Other names: interventional therapy;|
| Active Comparator: Endovascular treatment alone group<br>endovascular treatment alone | Other: Endovascular treatment<br>* endovascular treatment<br>* Other names: interventional therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin scale score | disability level | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients non-disabled (mRS score 0 to 1) or return to pre-morbid mRS score at 90 days (for patients with mRS > 1) | excellent outcome | 90 days | 
| Proportion of patients functionally independent (mRS score 0 to 2) at 90 days | functional independence | 90 days | 
| Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3) | ambulatory or bodily needs-capable or better | 90 days | 
| Substantial reperfusion at initial angiogram | evaluate effect of tenecteplase on reperfusion | within 5 minutes at initial angiogram | 
| Revascularization rates at 48 hours from randomization | evaluate vascular patency after treatment | at 48 hours from randomization | 
| Early neurologic improvement | Early neurologic improvement was defined as a reduction of 8 points in the NIHSS score between baseline and 72 hours or as a score of 0 or 1 at 72 hours. An 8-point reduction is considered to be highly clinically significant | 72 hours | 
| Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L) | Health-related quality of life | 90 days | 
| Symptomatic/Asymptomatic intracranial hemorrhage within 48 hours | evaluate intracranial hemorrhage | within 48 hours after endovascular treatment | 
| Mortality within 90 days | evaluate death rate of the two treatment groups | 90 days | 
| Parenchymal hematoma | evaluate intracranial hemorrhage | within 48 hours after endovascular treatment | 
| Procedural-related complications and severe adverse events | evaluate complications and any adverse events | within 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombolysis, Endovascular treatment, rhTNK-tPA