Determination of the Best Therapeutic Strategy, Interventional With Best Medical Management (BMM) Versus BMM Alone, for Patients With Symptomatic Moderate <70% Atherosclerotic Carotid Artery Stenosis: the SIMCA Multicenter Randomized Trial

N/ANot Yet RecruitingNCT07839390

Central Hospital, Nancy, France1,440 enrolled

Overview

Stroke is one of the leading causes of death and the main cause of long-term disability worldwide. A frequent cause is the narrowing of the carotid artery due to atherosclerosis, known as carotid artery stenosis. When stenosis is moderate (\< 70%) and has already caused symptoms, the best strategy to prevent another stroke remains uncertain. Earlier studies compared surgery or stenting with medical therapy, but these trials were conducted before modern medical treatments were available and did not consider important plaque characteristics that may increase the risk of recurrence. As a result, current clinical practice varies widely, and existing guidelines are based on low-quality evidence. The SIMCA trial aims to address this gap by comparing two treatment strategies in patients with symptomatic moderate carotid stenosis : best medical management (BMM) alone versus BMM combined with an intervention (endarterectomy or stenting). The primary objective is To determine whether intervention (endarterectomy or stenting) plus BMM compared to BMM alone significantly reduces the incidence of ipsilateral symptomatic cerebral infarction in patients with symptomatic atherosclerotic moderate stenosis of the cervical internal carotid artery at 5 years Hypothesis : The arm of this study is therefore to determine the best therapeutic strategy between intervention with best medical management (BMM) versus BMM alone (main objective) and the best intervention (endarterectomy or stenting) (secondary objective) to prevent cerebral infarction in patients with symptomatic atherosclerotic moderate (\< 70%) CAS.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,440

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Age ≥ 18 years * Modified Rankin Score 0 to 3 * Atherosclerotic stenosis of the cervical internal carotid artery with * Between 50-69% (NASCET method) confirmed by computed tomography angiography (CTA) or magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) OR * Stenosis \< 50% (NASCET method) confirmed by CTA or MRA or DSA with at least one of the following markers of high-risk carotid plaque features for stroke recurrence (vulnerable plaque), possibly identified by doppler ultrasound: * intra-plaque hemorrhage * irregular plaque surface defined as an indentation, fissure, erosion, or ulceration on the luminal surface of the plaque * lipid-rich necrotic core (LRNC) occupying ≥50% plaque4. Symptomatic stenosis defined as clinical signs due to * ipsilateral ischemic stroke documented on cerebral imaging OR Ipsilateral permanent or transitory retinal embolic infarction document by ophthalmologic examination OR transient ischemic attack defined as transient motor deficit and/or aphasia. AND * obviously due to the atherosclerotic stenosis: in a concordant territory, excluding lacunar infarction, and associated cardio embolic source (atrial fibrillation excluded by ECG, and 24-hour monitoring or holter), and multiterritorial simultaneous cerebral infarctions AND * within 14 days before planned intervention * For whom both kinds of intervention (endarterectomy and stenting) are allowed. * Able and willing to give consent * Person affiliated to or beneficiary of a social security plan Exclusion criteria: * Expected survival \<5 years (renal clairance MDRD \<30 mL/min/1.73m2, severe cardiac or respiratory insufficiency, active cancer) * Patient unable to undergo any of both carotid revascularization (endarterectomy or stenting) * Atrial fibrillation or medical history of atrial fibrillation * Carotid artery stenosis due to radiotherapy * Tandem lesion defined with the association of a severe intracranial stenosis (degree above the determining cervical internal carotid artery stenosis) or complete occlusion * History of revascularization procedure on the determining internal carotid artery * Contra indication to dual antiplatelet therapy * Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the Public Health Code: * Pregnant, parturient or breastfeeding woman * Minor person (non-emancipated) * Adult person under legal protection (any form of public guardianship) * Person deprived of liberty for judicial or administrative decision, person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1

Outcomes

Primary Outcomes

Any stroke or death during the periprocedural period, or ipsilateral symptomatic cerebral infarction during long-term follow-up

* Any stroke or death during the periprocedural period (within 30 days after procedure) * Or symptomatic cerebral or retinal infarction ipsilateral to stenosis during long-term follow-up (5 years)

Time frame: 30 days after procedure and up to 5 years

Secondary Outcomes

Ipsilateral symptomatic cerebral or retinal infarction

occurance of Ipsilateral symptomatic cerebral infarction after randomization

Time frame: 5 years follow-up

Any symptomatic ischemic stroke,

Occurance of any symptomatic ischemic stroke

Time frame: 5 years follow-up

Any symptomatic stroke

Occurrence of symptomatic stroke (ischemic or hemorrhagic),

Time frame: 5-year follow-up:

Myocardial infarction,

Occurence of myocardial infarction,

Time frame: 5 years follow up

Vascular death,

Death atttributed to a vascular cause

Time frame: 5 years follow up

Cranial narve palsy

Occurence of paralysis of any last cranial nerve (ranked by frequency: XII, X, VII, IX, XI, or sympathic cervical nerve with Claude Bernard Horner syndrome)

Time frame: 5 years follow up

Functional outcome

Modified Rankin Scale (mRS) score,

Time frame: at 5 years

Health-related quality of live

Health-related quality of live assesed using EuroQol 5 Dimensions (EQ-5D-5L) questionnaire.

Time frame: At 5 years

Stroke or death during periprocedural phase or ipsilateral symptomatic cerebral or retinal infarction at 5-years

Composite of any stroke or death during the periprocedural period (within 30 days after the procedure), or ipsilateral symptomatic cerebral or retinal infarction during 5 years of follow-up

Time frame: periprocedural period (30 days) and 5 years follow-up

Arterial blood pressure as Best Medical Management (BMM) compliance

compliance with best medical management assessed from • Arterial blood pressure (mmHg)

Time frame: 5 years

Low Density Lipoprotein (LDL) cholesterol level as Best Medical Management (BMM) compliance

compliance with best medical management assessed from • Low Density Lipoprotein (LDL) cholesterol level (g/L or mmol/L)

Time frame: 5 years

Glycated haemoglobin level as compliance with Best Medical Management (BMM) compliance

Compliance with best medical management assessed from routine clinical bioliological data Glycated haemoglobin level (%)

Time frame: 5 years

Tobacco cessation as Best Medical Management (BMM) compliance

Compliance with best medical management assessed from routine assessment : • Tobacco cessation or consumption (YES/NO)

Time frame: 5 years

Alcohol consumption as as Best Medical Management (BMM) compliance

Compliance with best medical management assessed from routine assessment : • Alcohol consumption (drinks/week)

Time frame: 5 years

Daily physical activity assessment as best Medical Management (BMM) compliance

compliance with best medical management assessed from routine clinical assessment : • Daily physical activity assessment (hours/week)

Time frame: 5 years

Any stroke or death during the periprocedural period, or ipsilateral symptomatic cerebral infarction during 2-Year follow-up

* Any stroke or death during the periprocedural period (within 30 days after procedure) * Or symptomatic cerebral or retinal infarction ipsilateral to stenosis during long-term follow-up (2 years)

Time frame: 30 days after procedure and up to 2 years

Ipsilateral symptomatic cerebral or retinal infarction at 2-years

occurance of Ipsilateral symptomatic cerebral infarction after randomization

Time frame: 2 years follow-up

Any symptomatic ischemic stroke at 2-years

Occurance of any symptomatic ischemic stroke

Time frame: 2 years follow-up

Any symptomatic stroke at 2-years

Occurrence of symptomatic stroke (ischemic or hemorrhagic),

Time frame: 2 years follow-up:

Myocardial infarction at 2-years

Occurence of myocardial infarction,

Time frame: 2 years follow up

Vascular death at 2-years

Death atttributed to a vascular cause

Time frame: 2 years follow up

Cranial narve palsy at 2-years

Occurence of paralysis of any last cranial nerve (ranked by frequency: XII, X, VII, IX, XI, or sympathic cervical nerve with Claude Bernard Horner syndrome)

Time frame: 2 years follow up

Functional outcome at 2-years

Modified Rankin Scale (mRS) score,

Time frame: at 2 years

Health-related quality of live at 2-years

Health-related quality of live assesed using EuroQol 5 Dimensions (EQ-5D-5L) questionnaire.

Time frame: At 2 years

Stroke or death during periprocedural phase or ipsilateral symptomatic cerebral or retinal infarction at 2-years

Composite of any stroke or death during the periprocedural period (within 30 days after the procedure), or ipsilateral symptomatic cerebral or retinal infarction during 5 years of follow-up

Time frame: periprocedural period (30 days) and 2 years follow-up

Arterial blood pressure as Best Medical Management (BMM) compliance at 2-years

compliance with best medical management assessed from • Arterial blood pressure (mmHg)

Time frame: 2 years

Low Density Lipoprotein (LDL) cholesterol level as Best Medical Management (BMM) compliance at 2-years

compliance with best medical management assessed from • Low Density Lipoprotein (LDL) cholesterol level (g/L or mmol/L)

Time frame: 2 years

Glycated haemoglobin level as compliance with Best Medical Management (BMM) compliance at 2-years

Compliance with best medical management assessed from routine clinical bioliological data Glycated haemoglobin level (%)

Time frame: 2 years

Tobacco cessation as Best Medical Management (BMM) compliance at 2-years

Compliance with best medical management assessed from routine assessment : • Tobacco cessation or consumption (YES/NO)

Time frame: 2 years

Alcohol consumption as as Best Medical Management (BMM) compliance at 2-years

Compliance with best medical management assessed from routine assessment : • Alcohol consumption (drinks/week)

Time frame: 2 years

Daily physical activity assessment as best Medical Management (BMM) compliance at 2-years

compliance with best medical management assessed from routine clinical assessment : • Daily physical activity assessment (hours/week)

Time frame: 2 years

Determination of the Best Therapeutic Strategy, Interventional With Best Medical Management (BMM) Versus BMM Alone, for Patients With Symptomatic Moderate <70% Atherosclerotic Carotid Artery Stenosis: the SIMCA Multicenter Randomized Trial

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts