Stent Implantation Versus Balloon Dilation for Acute Anterior Circulation Tandem Occlusion

Study Overview
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Brief Summary
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To evaluate whether stent implantation on the ipsilateral extracranial segment, after intracranial thrombectomy successful recanalization compared with balloon angioplasty (eTICI≥2b_50) for acute anterior circulation tandem lesions within 24h of onset, can improve neurological functional outcomes(mRS≤2). To evaluate whether stent implantation on the ipsilateral extracranial segment, after intracranial thrombectomy successful recanalization compared with balloon angioplasty (eTICI≥2b_50) for acute anterior circulation tandem lesions within 24h of onset, can increase the risk of symptomatic intracranial hemorrhage.

Detailed Description
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The study was a prospective, randomized, open-label, blinded end-point Clinical Trial. Subjects were randomized 1:1 according to inclusion and exclusion criteria into a trial group (acute phase extracranial vascular stent implantation group) and a control group (acute phase non-extracranial vascular stent implantation group). Randomization was performed for 90d and 180d for the follow-up to collect primary and secondary efficacy and safety indicators.

Official Title
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Stent Implantation Versus Balloon Dilation for Acute Anterior Circulation Tandem Occlusion: A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial

Conditions
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Thrombectomy, Tandem Occlusion, Stroke

Intervention / Treatment
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* Device: Carotid Stenting
* Procedure: Thrombectomy
* Drug: Dual antiplatelet treatment
* Drug: Intraoperative Drug Treatment


Participation Criteria
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Eligibility Criteria
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General inclusion criteria Age 18-85 years old; Acute ischemic stroke and the onset time within 24h; Pre-stroke mRS 0-1; NIHSS score of 6-30 before randomization; Completed randomization within 24h after stroke onset； Subjects are able to sign an informed consent in person or by the legal representative Imaging Inclusion Criteria: Satisfy one of the following criteria:①Within 6 hours of onset, imaging confirmed occlusion of the acute anterior circulation internal carotid artery or the M1 / M2 segment of the middle cerebral artery；②Within 6-16 hours of onset, imaging confirmed acute occlusion of anterior circulation internal carotid artery or M1 / M2 segment of middle cerebral artery followed by DAWN or DEFUSE-3 criteria；③In patients with 16 to 24 hours of onset, imaging confirmed intracranial occlusion of the acute anterior circulation internal carotid artery or M1 / M2 segment of the middle cerebral artery followed by DAWN criteria. Extracranial segment stenosis ≥70% or occlusion in tandem lesions. ASPECT score ≥ 6 points. eTICI≥2b_50 after middle cerebral artery thrombectomy and extracranial balloon dilatation in 10min. General Exclusion Criteria: Participating in other clinical trials; 2.It is planned to carry out selective internal carotid artery stent implantation within 3 months; 3.Intracranial hemorrhage, subarachnoid hemorrhage within 3 months; previous brain tumor (with space-occupying effect). 4.Parenchymal organ surgery or biopsy were performed last 1 month; Any active or recent bleeding (gastrointestinal, urinary, etc.); Parenchymal organ surgery and biopsy were performed last 1 month 5.Difficult to control hypertension: systolic blood pressure> 185mmHg and/ or diastolic blood pressure> 110mmHg. 6.Severe active bleeding or known significant bleeding tendency: platelet count <100X109/L; heparin within 48 hours before surgery, and APTT≥35s; oral warfarin, and INR> 1.7; direct thrombin or factor Xa inhibitors, such as apixaban tablets, rivaroxaban tablets and dabigatran (patients with no history of abnormal coagulation or suspected abnormal coagulation function do not need laboratory results of INR or APTT before enrollment）. 7.Severe heart, liver, kidney, and other organ insufficiencies (glomerular filtration rate <30 ml/min or blood creatinine> 220μmol/L(2.5mg/dl)). 8.Patients occurred acute ischemic cerebral infarction within 48 hours after percutaneous coronary or cerebrovascular intervention or major surgery (if more than 48h, patients may be enrolled). 9. The patient has a history of cerebral vasculitis with clear evidence; 10. Patients with pre-onset neurological or psychiatric disorders that affect the assessment of their condition 11.Women who are known to be pregnant or lactating. 12.Known severe allergy to contrast agents (except for mild rash allergy) 13.Expected survival time less than 1 year (such as combined malignancy, severe cardiopulmonary disease, etc.) 14.Patients unable to complete the follow up (e. g., no fixed residence, overseas patients, etc.). Imaging exclusion criterias: Imaging confirmed the posterior circulatory lesions. Midline displacement of the brain or brain herniation, ventricular occupancy New onset bilateral acute stroke or multiple intracranial macrovascular occlusions. Patients with vascular variants that are difficult to treat with endovascular therapy as displayed by CTA/MRA; The ipsilateral middle cerebral artery and anterior cerebral occlusion were combined.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: Carotid artery stenting after intracranial or middle cerebral artery embolization and balloon dilation of the extracranial segment of the ipsilateral internal carotid artery
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombectomy + Carotid Stenting<br>After emergency admission,intravenous thrombolysis will be administered if possible. Standard endovascular thrombectomy (EMT) and balloon angioplasty will be performed. The method of EMT and the order of endovascular treatment were selected by each center. After EMT and balloon angioplasty, patients with eTICI≥2b_50 were maintained for more than 10 minutes for randomization. In the intervention arm, emergent carotid stenting will be performed. Standardized treatment with antiplatelet and other drugs will be given. A loading dose of antiplatelet agents (aspirin 300 mg and clopidogrel 300 mg) or Tirofiban was given as an intraoperative drug treatment to endovascular therapy prior to emergency balloon dilation or stenting. Intravenous sedation or general anesthesia will be permitted. Oral dual antiplatelet treatment for more than 1 month. Tirofiban is maintained for 24-48 hours, overlapping with oral antiplatelet for 4-6 hours, after excluding intracranial hemorrhage. | Device: Carotid Stenting<br>* Emergent carotid stenting will be performed if the patient is randomized in the intervention arm. The order to treat (head first or neck first) the extracranial carotid artery lesion will be left to the interventionist discretion.<br>Procedure: Thrombectomy<br>* Intracranial thrombectomy is an endovascular procedure. In the experimental group, thrombectomy will be completed with extracranial carotid stenting.<br>Drug: Dual antiplatelet treatment<br>* Dual antiplatelet therapy is administered after 24 hours of imaging follow-up excluding intracranial hemorrhagic complications. Aspirin Enteric-coated Tablets (Bay Aspirin) 100mg once a night+Clopidogrel Sulfate Tablets (Plavix) 75mg once daily. If there is no contraindication, maintain for more than 1 month, then adjust the dosing regimen according to the guidelines.<br>Drug: Intraoperative Drug Treatment<br>* Tirofiban is used as an adjunct to endovascular therapy. The currently recommended dosing regimen is a combined intra-catheter arterial administration of a loading dose of 0.4 μg/(kg-min) for 30 min (total dose not to exceed 1 mg)， followed by intravenous pumping of 0.1μg/(kg-min) for 24-48h, and adjustment of dosing in conjunction with CT.<br>|
| No Intervention: Thrombectomy alone<br>Intracranial thrombectomy alone（balloon dilation of the ipsilateral internal carotid artery if necessary） | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of functional independence | Rate of functional independence defined as a modified Rankin Scale (mRS) score 0-2 at 90 (±7 days) (blind and independent evaluation) The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge. | at 90±7 days | 
| Rate of symptomatic intracranial hemorrhage | Rate of symptomatic intracerebral hemorrhage at CT (Computerized Tomography) or MRI (Magnetic Resonance Imaging) at 36 hours (±12 hours) according to the Heidelberg classification (independent imaging core laboratory). | at 36 hours (±12 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The expanded treatment in cerebral infarction (eTICI) score | eTICI score (0,1,2a,2a_50,2a_67,2c,3) : Grade 0 : no perfusion Grade 1: penetration with minimal perfusion Grade 2a: partial filling of 1-49% of the vascular territory Grade 2b_50 : partial filling of 50-66% of the vascular territory Grade 2b_67: partial filling of 67-89% of the vascular territory Grade 2c: partial filling of 90-99% of the vascular territory Grade 3 : complete perfusion | at the end of the endovascular procedure | 
| Ipsilateral carotid residual stenosis rate | The extracranial stenosis was assessed by using criteria from the North American Symptomatic Carotid Endarterectomy Trial (NASCET). The residual stenosis rate of the ipsilateral internal carotid artery was assessed according to the last DSA angiography of the procedure. | at the end of the endovascular procedure | 
| The National Institutes of Health Stroke Scale (NIHSS) score | National Institutes of Health Stroke Scale (NIHSS) score. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient. Higher scores mean a worse outcome. | at 36 hours (±12 hours) | 
| Proportion of NIHSS scores 0-1 | The proportion of patients with an NIHSS score of 0-1 National Institutes of Health Stroke Scale (NIHSS) score. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient. Higher scores mean a worse outcome. | at 36 hours (±12 hours) | 
| Change in National Institutes of Health Stroke Scale (NIHSS) score | The proportion of patients with an NIHSS score reduction of ≥4 points after randomization compared to baseline. NIHSS is 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Higher scores mean a worse outcome. | at 36 hours (±12 hours) | 
| Rate of carotid stenosis | The extracranial stenosis was assessed by using criteria from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) confirmed by cervical vascular ultrasound. | at 5-7days or discharge | 
| The NIHSS score | The NIHSS score NIHSS is 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. Higher scores mean a worse outcome. | at 5-7days or discharge | 
| The mRS scores | The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge. | at 90±7days and 180±14 days | 
| Proportion of mRS score 0-3 | The Modified Rankin Score (mRS) is a 6-point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain an mRS score are recommended at 3 months (90 days) following hospital discharge. Higher scores mean a worse outcome. | at 90±7days and 180±14 days | 
| All-cause mortality | Rate of mortality at 90±14 days. | at 90±7days | 
| Rate of asymptomatic intracranial hemorrhage | Rate of symptomatic intracerebral hemorrhage at CT (Computerized Tomography) or MRI (Magnetic Resonance Imaging) at 36 hours (±12 hours) according to the Heidelberg classification (independent imaging core laboratory). | at 36 hours (±12 hours) | 
| The incidence of adverse events. | Any adverse medical event, whether causally related to the trial or not, that occurred between the start of patient randomization and the last follow-up visit was judged as an adverse event. The incidence of non-hemorrhagic adverse events. | at 90±7days and 180±14 days | 
| The incidence of serious adverse events. | A serious adverse event is defined as an adverse event that results in Resulting in death; Life-threatening (means that the subject is at risk of death at the time of an adverse event. It does not refer to those adverse events that could lead to death if the condition were assumed to be worse); Requires hospitalization or prolonged hospitalization; Resulting in persistent or severe disability or dysfunction Resulting in a congenital anomaly or birth defect; Medical events that, in the opinion of the investigator, can be judged as serious adverse events. The incidence of non-hemorrhagic serious adverse events. | at 90±7days and 180±14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tandem occlusion, anterior circulation, stent implantation, balloon dilation, randomized controlled trial