Evaluation of Mechanical Thrombectomy in Acute Ischemic Stroke Related to a Distal Arterial Occlusion

Study Overview
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Brief Summary
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Mechanical thrombectomy (MT) has shown its effectiveness for the treatment of acute ischemic stroke (AIS) related to large vessel occlusion and rapidly became a cornerstone in the management of these patients. No strong evidence is available on the benefit of MT in AIS related to more distal occlusions. Some previous observational studies suggested a possible benefit but most of them were single-centre and retrospective studies providing a very low level of evidence. To date, no randomized controlled trial has been conducted in this indication, which represents 10% to 20% of all AIS involving intracranial vessel occlusions. This research is a multicenter open randomized controlled trial with two parallel groups : best medical treatment alone VS mechanical trombectomy + best medical treatment.

Detailed Description
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The main objective of this trial is to assess the efficacy of mechanical thrombectomy in addition to the best medical treatment as compared to the best medical treatment alone in AIS related to a distal intracranial artery occlusion. The medical device used will be a stent retriever among : Trevor NXT ProVue Retriever ; Catchview mini ; pReset Lite ; Tigertriever13, and the medical treatment used will depend on the stroke's etiology and will consist of IV trhombolysis or tenecteplase or antiplatelet therapy or anticoagulant therapy ... The main inclusion criteria are : 1) patients aged ≥ 18 years ; 2) Delay between symptoms onset and expected groin puncture ≤ 6h ; 3) Symptomatic occlusion as evaluated by a National Institute of Health Stroke Score (NIHSS) ≥ 5 ; 4) Distal occlusion evaluated on CT angiography (CTA) or magnetic resonance imaging (MRI) and defined as an occlusion in one of the following segments : a-Distal M2, above the mid-height of the insula, b-M3 segment, c-Posterior cerebral artery (PCA) = P1, P2 or P3 segment, d-Anterior cerebral artery (ACA) : A1, A2 or A3 segment ; 5) Written informed consent signed by the patient or the trustworthy person / family member / close relative, or inclusion in case of emergency and written informed consent will be signed by the patient (if needed by trustworthy person, family member or close relative) as soon as possible (article L1122-1-2 of the French Public Health Code). The secondary objectives and endpoints are to evaluate the : 1) Success of the procedure defined as recanalization of the occluded vessel, evaluated on the AOL (Arterial Occlusion Lesion) score within 48 hours ; 2) Excellent clinical outcome (defined as a modified Rankin scale [mRS]≤1) at 3 months ; 3) Safety with reporting of all adverse and serious adverse events with a particular attention to perforation rate, embolus migration in a new territory and symptomatic hemorrhagic complications ; 4) Death rate up to 3 months ; 5) Cost effectiveness and utility of the procedure. The study will also evaluate the rate of angiographic reperfusion in the intervention group on the final angiogram at the end of the MT (which is part of the intervention) using the modified thrombolysis in cerebral infarction (mTICI) (2B-3) and the eTICI.

Official Title
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Evaluation of Mechanical Thrombectomy in Acute Ischemic Stroke Related to a Distal Arterial Occlusion: a Randomized Controlled Trial

Conditions
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Acute Ischemic Stroke (AIS) Related to a Distal Occlusion

Intervention / Treatment
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* Procedure: Mechanical Thrombectomy
* Drug: Best medical treatment alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years Delay between symptoms onset and expected groin puncture ≤ 6 h Symptomatic occlusion as evaluated by a National Institute of Health Stroke Score (NIHSS) ≥ 5 Distal occlusion evaluated on CT angiography (CTA) or magnetic resonance imaging (MRI) and defined as an occlusion in one of the following segments: Distal M2, above the mid-height of the insula M3 segment Posterior cerebral artery (PCA): P1, P2, P3 segments Anterior cerebral artery (ACA): A1, A2, A3 segments Written informed consent signed by the patient or the trustworthy person / family member / close relative, or inclusion in case of emergency and written informed consent will be signed by the patient (if needed by trustworthy person, family member or close relative) as soon as possible (article L1122-1-2 of the French Public Health Code) Exclusion Criteria: Pregnancy or breastfeeding woman Contra-indication for femoral, radial or humeral arterial puncture Tandem occlusion (i.e.: concomitant cervical and intra-cranial arterial occlusion) Allergy to iodinated contrast media Known renal insufficiency (confirmed by previous result of creatinine clearance < 30 ml/min) Secondary distal occlusion (i.e., complicating a MT for a proximal occlusion, or any other endovascular intracranial procedure) Aortic dissection Asymptomatic or minor stroke (i.e.: NIHSS < 5) Pretreatment mRS > 1 (pre-stroke) Anticipated limitations for anesthesia Participation in another trial (Jardé 1 and Jardé 2) Absence of affiliation to National French social security system Under legal protection measure (tutorship or curatorship) and patient deprived of freedom A pre-existing hemorrhage in the brain tissue fed by the target vessel Known hypersensitivity to nickel/titanium Stenosis and/or with a stent proximal to the site of the thrombus which could preclude the retrieval of the stent retriever Angiographic evidence of carotid dissection

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mechanical thrombectomy<br>Mechanical thrombectomy (using a stent retriever among the following:Trevo NXT ProVue Retriever, Catchview mini, pReset Lite, Tigertriever 13) in association with the best medical treatment (usual care) | Procedure: Mechanical Thrombectomy<br>* Mechanical thrombectomy (using a stent retriever among the following:Trevo NXT ProVue Retriever, Catchview mini, pReset Lite, Tigertriever 13) in association with the best medical treatment (usual care)<br>* Other names: Experimental group;|
| Active Comparator: Active Comparator<br>Best medical treatment alone (usual care) | Drug: Best medical treatment alone<br>* Best medical treatment alone (usual care)<br>* Other names: Control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Good clinical outcome (defined as a modified Rankin Scale [mRS] ≤ 2) | mRS of 0-2 (evaluated by an independent assessor blinded to the intervention received by the patient) | At 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recanalization of the occluded vessel | Evaluation of AOL (Arterial Occlusion Lesion scale) ≥ 2 on vascular brain imaging (magnetic resonance MR) or computed tomography (CT) angiography in patients belonging to both arms | 48 hours after the mechanical thrombectomy | 
| Angiographic reperfusion in the intervention group | Use of the mTICI score (successful reperfusion: mTICI 2b-3) and the eTICI (extended thrombolysis in cerebral infarction) score (successful reperfusion: eTICI ≥ 2b67) on the control digital subtraction angiography (DSA) | End of the mechanical thrombectomy procedure | 
| Excellent Clinical outcome (defined as a modified Rankin Scale [mRS] ≤ 1) | mRS of 0-1 (evaluated by an independent assessor blinded to the intervention received by the patient) | At 3 months | 
| Perforation rate | Defined as contrast material extravasation either on digital subtraction angiography [DSA] or control CT scan | End of mechanical thrombectomy procedure | 
| Embolus migration in a new territory | evaluated on digital subtraction angiography [DSA] | End of mechanical thrombectomy procedure | 
| Symptomatic intracranial hemorrhage | evaluated on CT-scan or MRI according to the ECASS II criteria | within 7 days | 
| Subarachnoid hemorrhage | evaluated on CT-scan or MRI and define as the abnormal presence of blood within the subarachnoid space presence of blood within the subarachnoid space | within 48 hours | 
| Safety : incidence of adverse events | Reporting of all adverse events | At 3 months | 
| Safety : incidence of serious adverse events | Reporting of all serious adverse events | At 3 months | 
| Death rate | Mortality | At 3 months | 
| Utility of the procedure | Incremental cost utility ratio | At 3 months | 
| Cost effectiveness | Cost per additional survivor (health-economics analysis) | At 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, Distal occlusions, Mechanical Thrombectomy