Basilar Artery Occlusion Chinese Endovascular Trial

Study Overview
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Brief Summary
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Endovascular treatment of acute ischemic stroke has shown strong benefit in several prospective randomized trials in the anterior circulation and endovascular therapy for basilar artery occlusion has shown promising results in several single-arm studies. This has led to a broad adoption of these techniques which are now considered standard of care in many institutions despite the lack of adequate evidence to prove their benefit. Indeed, the rates of symptomatic intracerebral hemorrhage in these studies have consistently been around 5% which raises the question as to whether patients could actually be harmed as opposed to helped by these procedures. This is a prospective, multi-center, randomized, controlled, open, blinded-endpoint trial, with the aim to evaluate the hypothesis that mechanical embolectomy with the Solitaire device is superior to medical management alone in achieving better outcomes in subjects presenting with an acute ischemic stroke caused by occlusion of the basilar artery within 6-24 hours from symptom onset.

Detailed Description
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Study Objective: To evaluate the hypothesis that mechanical embolectomy with the Solitaire device is superior to medical management alone in achieving favourable outcomes defined as modified Rankin score (mRS) 0-3 at 90 days in subjects presenting with ischemic stroke due to basilar artery occlusion up to 24 hours from symptom onset. Subject Population: Subjects presenting with acute ischemic stroke within 6-24 hours from symptom onset/last seen well and whose strokes are attributable to an occlusion of the basilar artery. Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. The randomization employs a 1:1 ratio of mechanical embolectomy with Solitaire stentriever in conjunction with manual aspiration versus medical management alone. Randomization will be done under a stratification process using age, baseline National Institute of Health Stroke Scale (NIHSS) and therapeutic window. For the primary endpoint, subjects will be followed for 90 days post-randomization.Sample size is projected to be 318 patients. Care providers: Vascular neurologists and trained interventional neuroradiologists or neurologists in certified comprehensive stroke centers that treat more than 500 acute stroke patients and perform more than 30 acute mechanical thrombectomies every year will treat patients. Neurointerventionalists have to have previously performed at least 10 thrombectomies with Solitaire device in acute ischemic stroke patients. Interventions: Patients in both arms will be admitted at acute stroke units (or Intensive Care Unit if needed) and treated following the Chinese Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Concomitant medications and non-pharmacological therapies will be recorded. If a decision of stopping support life measures is adopted, this will be recorded in the Case Report Form (CRF).A maximum of six attempts to retrieve the thrombus in a single vessel can be made with any Solitaire device or aspiration. In case an atherosclerotic lesion is found underlying the occlusive lesion angioplasty/stenting through detachment of the Solitaire device will be allowed.

Official Title
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Randomized Trial of Revascularization With Solitaire Stentriever Versus Best Medical Therapy in the Treatment of Acute Ischemic Stroke Due to Basilar Artery Occlusion Presenting Within 6-24 Hours of Symptom Onset

Conditions
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Basilar Artery Occlusion, Ischemic Stroke, Cerebrovascular Disorders

Intervention / Treatment
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* Procedure: Mechanical embolectomy
* Drug: Medical Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Posterior circulation AIS within 6-24 hours from symptom onset/last seen well where patient is ineligible for i.v. thrombolytic treatment, or patient has received i.v. thrombolytic therapy without recanalization. Occlusion (Thrombolysis in Myocardial Infarction, TIMI 0-1) of the basilar artery or intracranial segments of both vertebral arteries as evidenced by computed tomography (CT) angiography, magnetic resonance (MR) angiography or angiogram. Age ≥18 and ≤80 years. Baseline National Institutes of Health Stroke Scale (NIHSS) score obtained prior to randomization must be equal to or higher than 6 points. No significant pre-stroke functional disability (modified Rankin Scale, mRS ≤ 1). Patient treatable within 24 hours from time last seen well. Isolated vertigo with nausea and/or vomiting is not considered onset of symptom. Informed consent obtained from patient or acceptable patient surrogate. Exclusion criteria General Exclusion Criteria: Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with international normalized ratio > 3.0. Baseline platelet count < 50.000/µL. Baseline blood glucose < 50mg/dL or > 400mg/dL. Severe, sustained hypertension (systolic blood pressure > 220 mm Hg or diastolic blood pressure > 110 mm Hg). Patients in sedation and/or intubated patients could not be included if baseline NIHSS is not obtained by a neurologist or emergency physician prior to sedation or intubation. Seizures at stroke onset which would preclude obtaining a baseline NIHSS. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year. History of life threatening allergy (more than rash) to contrast medium Subjects who has received i.v. tissue plasminogen activator (t-PA) treatment beyond 4.5 hours from the beginning of the symptoms. Patients with acute stroke within the first 48 hours after percutaneous cardiac, cerebrovascular interventions and major surgery (beyond 48h they should be randomized in BAOCHE or excluded for endovascular treatment if poor medical conditions). Renal insufficiency with creatinine ≥ 3 mg/dl. Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission. Subject participating in a study involving an investigational drug or device that would impact this study. Cerebral vasculitis. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations; mRS score at baseline must be ≤ 1. Unlikely to be available for 90 days follow-up. Neuroimaging Exclusion Criteria: Hypodensity amounting to a posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) < 6 and Pons-midbrain-index of ≥ 3 on CT angiography source images or MR with diffusion-weighted imaging or NCCT. CT or MR evidence of hemorrhage (the presence of microbleeds on MRI is allowed). Complete cerebellar infarct on CT or MRI with significant mass effect and compression of the fourth ventricle. Complete unilateral or bilateral thalamic infarction on CT or MRI Evidence of vertebral occlusion, high grade stenosis or arterial dissection in the extracranial or intracranial segment that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment. Subjects with occlusions in both anterior and posterior circulation. Evidence of intracranial tumor (except small meningioma).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Endovascular Arm<br>Mechanical embolectomy with Solitaire stentriever in conjunction with manual aspiration Best Medical Treatment and maximum supportive care | Procedure: Mechanical embolectomy<br>* Mechanical embolectomy with Solitaire stentriever in conjunction with manual aspiration<br>Drug: Medical Treatment<br>* Best Medical Treatment and maximum supportive care, not including mechanical thrombectomy, no intra arterial treatment<br>|
| Other: Control Arm<br>Best Medical Treatment and maximum supportive care, not including mechanical thrombectomy, no intra arterial treatment | Drug: Medical Treatment<br>* Best Medical Treatment and maximum supportive care, not including mechanical thrombectomy, no intra arterial treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients achieving favourable outcomes defined as mRS 0-3 at 90 days | The primary objective of this study is to evaluate the hypothesis that mechanical embolectomy with the Solitaire device is superior to medical management alone in achieving favourable outcomes (mRS ≤ 3) at 90 days in subjects presenting with an acute ischemic stroke caused by occlusion of the basilar artery within 6-24 hours from symptom onset. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dramatic early favorable response | Dramatic early favorable response as determined by an National Institute of Health stroke scale (NIHSS) of 0-2 or NIHSS improvement ≥ 8 points at 24 (-2/+12) hours. | 24 (-2/+12) hours | 
| Dichotomized mRS score (0-2 versus 3-6 and 0-4 versus 5-6 ) |  | 90 days | 
| Proportion of patients achieving meaningful outcomes defined as mRS 0-4 at 12 months. |  | 12 months | 
| Final infarct volume and the change of infarct volume compared with baseline | Infarct volume evaluated on Computed Tomography (CT) or Magnetic Resonance (MR) at 24 hours (-2/+12 hours) | 24 hours (-2/+12 hours) | 
| Vessel recanalization with Arterial Occlusive Lesion (AOL) grades | Vessel recanalization at 24 hours (-2/+12 hours) in both treatment groups assessed by using Arterial Occlusive Lesion (AOL) grades | 24 hours (-2/+12 hours) | 
| Modified Rankin Score (mRS) |  | 90 days | 
| Barthel Index |  | 90 days | 
| NIHSS |  | 90 days | 
| Quality of life analysis | Quality of life analysis as measured by EuroQol/EQ5D and SF-36 at 3 month, 6 months and 1 year, between interventional therapy vs medical therapy alone | 3 month, 6 months and 1 year | 
| Mortality |  | at 90 days | 
| Symptomatic intracranial hemorrhage （SICH） |  | 24 (-2/+12) hours | 
| Serious Adverse Events |  | 1 year | 
| Montreal Cognition Test (MOCA) |  | 90 days | 
| Immediate Post-Endovascular Treatment Recanalization (for the Solitaire arm only) | Successful recanalization is defined as TICI (Thrombolysis in Cerebral Infarction) 2b or 3 in the post-procedure angiography. | Immediate Post-Endovascular Treatment | 
| Procedural related complications | arterial perforation, arterial dissection, embolization in a previously uninvolved vascular territory and so on. | Perioperative period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Basilar Artery Occlusion, Ischemic Stroke, Mechanical Embolectomy