Evaluation of Acute Endovascular Treatment in Symptomatic Isolated Cervical Internal Carotid Artery Occlusion Within 24 Hours of Last Seen Well (ETICA)

Study Overview
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Brief Summary
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Our main hypothesis is that acute EVT associated with best medical treatment is superior to best medical treatment alone, for improving clinical outcomes at 90 days, in patient with mild or severe AIS and diffusion-perfusion or clinical-imaging mismatch, secondary to CICAO.

Detailed Description
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The primary objective of this study is to demonstrate the superiority of endovascular therapy (EVT) associated with best medical therapy (BMT) compared to BMT alone to increase the functional independence at 3 months in patients with acute cervical isolated internal carotid artery occlusion (CICAO), mild to severe stroke (NIHSS score > 5), and core-perfusion or clinical-imaging mismatch. Secondary objectives are,(i) to compare the safety of EVT + BMT vs. BMT alone; (ii) to demonstrate the superiority of EVT + BMT vs BMT alone on : the rate of excellent outcome at 3 months (modified Rankin Scale, mRS, score = 0-1), the rate of recanalization at 24 hours and at day 90 post-randomization, the cerebral infarct size at 24 hours post-randomization, the early neurological deterioration rate at 24 hours and at day 7 post-randomization, the ischemic recurrences rate at day 90 post-randomization, the cognitive impairment rate at day 90 post-randomization. One of the secondary objective is also to describe in the experimental group (EVT + BMT), the procedure-related adverse events.

Official Title
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Evaluation of Acute Endovascular Treatment in Symptomatic Isolated Cervical Internal Carotid Artery Occlusion Within 24 Hours of Last Seen Well

Conditions
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Ischemic Stroke, Acute

Intervention / Treatment
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* Procedure: Endovascular treatment (EVT) + Best medical treatment (BMT)
* Procedure: Best medical treatment (BMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18-year-old patients (no upper age limit) Clinical signs consistent with AIS (Acute ischemic stroke), and time from last seen well to randomization ≤23h NIHSS score >5 at randomization time Ischemic stroke confirmed by cerebral imaging (CT: Computed Tomography or MRI:Magnetic Resonance Imaging) or normal imaging with suspected ischemic stroke Existence of a mismatch: If perfusion data are available (PWI/CTP), existence of a core-perfusion mismatch, suggestive of carotid hemodynamic mechanism, according to the DEFUSE-3 criteria: mismatch volume ≥15 mL, core volume ≤70 mL, and mismatch ratio ≥1.8 If perfusion data are not available, existence of a clinical-imaging mismatch, defined by an ASPECTS >5 (Alberta Stroke Program Early CT score) CICAO (Cervical isolated Internal Carotid Artery Occlusion) on CTA (Computed Tomography Angiography) or MRA with gadolinium, without associated visible ipsilateral large intracranial occlusion (T or L, M1, M2, A1, A2, P1, P2), <1 h after randomization Anticipated possibility to start the EVT procedure (arterial access) within 60 minutes after randomization Pre-stroke mRS score ≤2 Patient or patient's representative has received information about the study and has signed and dated the appropriate Informed Consent or met the criteria for emergency consent. Exclusion Criteria: CICAO after recent (<1 month) endarterectomy Patient with severe or fatal co-morbidities or life expectancy <6 months that will likely interfere with improvement or follow-up or that will render the procedure unlikely to benefit the patient Patient unable to come or unavailable for follow-up Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations Seizures at stroke onset if they make the diagnosis of stroke doubtful and preclude obtaining an accurate baseline NIHSS assessment Suspected cerebral vascular disease (e.g., vasculitis) based on the medical history and CTA/MRA Pregnancy in progress or planned during the study period, woman who is known to be pregnant or lactating at admission time Adult protected by law or patient under guardianship or curatorship Current participation in another investigational drug study Not affiliated to the French social security system or not beneficiary of such system Known contrast or endovascular product life-threatening allergy Associated stenosis (≥50%) of the middle cerebral artery ipsilateral to the CICAO Chronic CICAO, defined as a known carotid occlusion (on a previous imaging exam) ≥30 days before randomization Tandem occlusion, defined by cervical ICA occlusion associated with intracranial large vessel occlusion (T- or L-shaped, M1 or M2 portions of the middle cerebral artery, A1 or A2 portions of the anterior cerebral artery, P1 or P2 portions of the posterior cerebral artery) Associated ipsilateral large intracranial arterial occlusion Prior stenting of the target ICA Intracranial stent implanted in the same vascular territory as the CICAO Sub-occlusive cervical ICA stenosis on CTA or MRA Suspicion of ICA occlusion starting at the petrous, cavernous or intracranial segment with normal cervical portion on non-invasive imaging (MRA or/and CTA) Known absence of vascular access Suspicion of aortic dissection based on medical history, clinical evaluation or/and imaging Sub-occlusive cervical ICA stenosis on CTA or MRA Common carotid artery occlusion without ICA occlusion on non-invasive imaging (MRA or/and CTA) Evidence of intracranial hemorrhage on CT/MRI.

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
Interventional Model Description: The protocol is a national, multi-center, prospectively randomized into two parallel (1:1) arms, open to treatment with blinded endpoint trial (PROBE)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endovascular treatment + best medical treatment<br>Endovascular treatment associated with the best medical treatment. | Procedure: Endovascular treatment (EVT) + Best medical treatment (BMT)<br>* Endovascular treatment (EVT) in the experimental arm can be performed with any recanalization strategy based on the operator's choice, and anatomical and radiological situation: MT using aspiration or stent retriever, with or without stenting (CE-labelled) or angioplasty. In case of acute stenting, the use of antiplatelet drugs will be based on the operator's preference, anatomical situation, and risk of hemorrhage.<br>|
| Active Comparator: best medical treatment<br>Best medical treatment alone | Procedure: Best medical treatment (BMT)<br>* Administration of drugs is at the treating physician's discretion (for example, intravenous fibrinolysis, anticoagulants, or antiplatelet agents) according to the local standards of care, but not intra-arterial therapies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with favorable functional outcome, defined by a mRS score ≤2 | The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.The scale runs from 0 to 6, running from perfect health without symptoms to death. The mRS score will be evaluated by qualified assessors blinded to the initial treatment.The blinded evaluator must be familiar with mRS scoring (dedicated training and certification). If a participant is unable to attend in-person the follow-up visit at day 90 (±14), mRS scoring can be done by telephone by a qualified investigator. | Day 90 (± 14 days) post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with excellent outcome (mRS score = 0-1) | The mRS score will be evaluated by qualified assessors blinded to the initial treatment.The blinded evaluator must be familiar with mRS scoring (dedicated training and certification). If a participant is unable to attend in-person the follow-up visit at day 90 (±14), mRS scoring can be done by telephone by a qualified investigator. | Day 90 (± 14 days) post-randomization | 
| Change in NIHSS score at 24 (-6/+12) hours post-randomization. | NIHSS score is the National Institutes of Health Stroke Scale. The NIHSS is composed of 11 items, each of which scores a specific ability between 0 and 4. For each item, a score of 0 typically indicates normal function, while higher scores are indicative of some level of impairment. The individual scores for each item are summed to calculate the patient's total NIHSS score. The maximum possible score is 42, and the minimum score is 0. | 24h (-6/+12) post-randomization | 
| Quality of life assessed with the EuroQol 5D-5L scale | Assessed with the EuroQol 5D-5L scale. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems | Day 90 (± 14 days) post-randomization | 
| Cognitive function at day 90 (±14), evaluated with the MoCA test. | The MoCA test is the Montreal Cognitive Assessment mesuring the neurocognitive function. There are 30 questions covering orientation, short-term memory, focus and spatial awareness, language, concentration and clock drawing test. | Day 90 (±14 days) post randomization | 
| Ischemic recurrence rate | Ischemic recurrence rate | Day 5-7 post randomization | 
| Ischemic recurrence rate | Ischemic recurrence rate | day 30 (±5) post randomization | 
| Ischemic recurrence rate | Ischemic recurrence rate | day 90 (±14) post randomization | 
| Carotid artery revascularization rate | Assessed by angiography in the treatment arm, defined by complete recanalization or residual carotid artery stenosis <50% | randomization | 
| Carotid artery recanalization rate | Assessed by MRA with gadolinium or CTA, defined as complete recanalization or residual carotid artery stenosis <50% | 24 (-6/+12) hours post randomization | 
| Carotid artery recanalization rate | Assessed by MRA with gadolinium or CTA, defined as complete recanalization or residual carotid artery stenosis <50% | Day 90 (± 14 days) post-randomization | 
| Infarct volume | Mesured by magnetic resonance angiography (MRI, FLAIR) or computed tomography (CT). | 24 (-6/+12) hours post randomization | 
| Infarct volume | Mesured by magnetic resonance angiography (MRI, FLAIR) or computed tomography (CT). | Day 90 (± 14 days) post randomization | 
| Early neurological improvement | Early neurological improvement is defined by an NIHSS score of 0-2 at 24 hours or a ≥8-point decrease of the NIHSS score at 24 hours compared with baseline. | Day 0 - 24 hours post randomization | 
| Incidence of all-cause mortality at day 90 | Incidence of all-cause mortality at day 90 | Day 90 (± 14 days) post randomization | 
| Incidence of symptomatic intracranial hemorrhage | According to the Heidelberg Bleeding classification by brain imaging | 24 (-6/+12) hours post-randomization | 
| Incidence of procedure/device-related adverse events | In the experimental group (EVT + BMT) | Day 30 (±5 days) post randomization | 
| Early neurological deterioration rate | NIHSS score increase by ≥4 points | 24 hours post-randomization | 
| Neurological deterioration rate | NIHSS score increase by ≥4 points | Day 5-7 post randomization | 
| Rapid NIHSS worsening | NIHSS score increase by ≥10 points | Admission - day 5/day 7/discharge (if earlier) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic Stroke; Mechanical Thrombectomy; Carotid artery; Stenting, randomized trial