Collateral-based reSetting of Endovascular Treatment Time Window for Stroke (CoSETS)

Study Overview
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Brief Summary
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This study is a prospective, partly randomized, multi-center, Phase III, controlled trial, designed to show that the onset-to-puncture time (OPT) for good functional outcome (defined by modified Rankin Scale score at 3 months, 0-2) can be set depending on collateral status based on multiphase CT angiogram. The purpose of this study is to prove that (1) for patients with poor collaterals, there will no difference in good outcome rate between endovascular treatment and best medical treatment group if onset-to-puncture time is between 150 minutes and 600 minutes, and 2) for patients wih good collaterals, the rate of good outcome is equal to or greater than 42% (10% greater than historical control) if onset-to-puncture time is between 150 minutes and 600 minutes. Patients will initially be classified into 3 arms based on both collateral status on multiphase CT angiography and whether or not receiving endovascular thrombectomy: group 1, patients with good collaterals and receiving endovascular thrombectomy, 2) group 2a, patient with poor collaterals and receiving endovascular thrombectomy, and 3) group 2b, patients with poor collaterals and not receiving endovascular thrombectomy. Patients with good collaterals will receive endovascular thrombectomy (EVT) if onset-to-puncture time is between 150 minutes and 600 minutes after last seen well time. Of the patients with poor collaterals, they will be randomized into endovascular treatment and best medical treatment group, if onset-to-puncture time is between 150 minutes and 600 minutes, (onset-to-puncture time is not possible within 150 minutes but possible within 600 minutes after last seen well). Primary endpoint is the rate of good outcome at 3 months. The number of subjects needed with statistical power of 0.8 and alpha value of 0.025 is estimated 309 patients.

Official Title
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Collateral-based reSetting of Endovascular Treatment Time Window for Stroke (CoSETS)

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Procedure: endovascular thrombectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke Age ≥ 19 years old Modified Rankin Scale score before qualifying stroke, 0 or 1 Baseline National Institute of Health Stroke Scale, 5 or greater Baseline Alberta Stroke Program Early Computed Tomographic Sign, 6 or greater Documented occlusion of relevant intracranial internal carotid artery or middle cerebral artery M1 segment on multiphase CT angiogram Starting of endovascular treatment (femoral artery puncture) should be possible between 150 minutes and 600 minutes after last seen well time. Nonenhanced CT and multiphase CT angiogram should be obtained in the participating hospital If indicated, intravenous administration of tissue plasminogen activator should be given. Exclusion Criteria: Femoral puncture is impossible Pregnancy or positive on serum beta-hCG test Known uncontrollable allergic reaction to iodized contrast media Intracranial cerebral artery dissection Suspected chronic occlusion of the relevant intracranial large artery In hospital stroke Bilateral internal carotid artery or middle cerebral artery occlusion Underlying severe medical or surgical disease which may affect treatment response. Clinical follow is impossible because of social or medical problems.

Ages Eligible for Study
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Minimum Age: 19 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: Factorial Assignment
Interventional Model Description: Patients will be dichotomized into good collateral (group 1) and poor collateral group (group 2) according to collateral status assessed on multiphase CT angiography.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group 1: patients with good collateral<br> | |
| Experimental: Group 2a, patient with poor collaterals<br>Group 2 patients (poor collateral group) will be randomized into endovascular thrombectomy group (2a) and best medical treatment group (2b), if femoral puncture is possible between 150 minutes and 600 minutes after last seen well. | Procedure: endovascular thrombectomy<br>* Intervention description : Group 1: patients with good collateral, Group 2: patient with poor collateral Group 1 patients (good collateral group) will receive endovascular thrombectomy using stent retriever, aspiration catheter, or both, if femoral puncture is possible between 150 minutes and 600 minutes after last seen well. Group 2 patients (poor collateral group) will be randomized into endovascular thrombectomy group (2a) and best medical treatment group (2b), if femoral puncture is possible between 150 minutes and 600 minutes after last seen well.<br>* Other names: best medical treatment;|
| No Intervention: Group 2b, patients with poor collaterals<br>Group 2 patients (poor collateral group) will be randomized into endovascular thrombectomy group (2a) and best medical treatment group (2b), if femoral puncture is possible between 150 minutes and 600 minutes after last seen well. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of good functional outcome defined by modified Rankin Scale score 0 - 2 | The scale runs from 0-6, running from perfect health without symptoms to death 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead. | 90 days ± 14 days after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin Scale score |  | 90 days ± 14 days after enrollment | 
| NIHSS score |  | 24 hours after enrollment | 
| NIHSS score |  | 72 hours after enrollment | 
| NIHSS score |  | 7 days after enrollment |