CEST-PROTECT: Proximal Flow Control With a Balloon Guide Catheter Plus Distal Embolic Protection: a Randomised, Open-label Trial Evaluating Cerebral Protection Techniques (CEST-PROTECT)

Inclusion Criteria:

1. Age 18 to 80 years, regardless of sex.
2. Symptomatic carotid artery stenosis ≥50% or asymptomatic carotid artery stenosis ≥70%, with the degree of stenosis determined according to the prespecified NASCET method and confirmed by CTA, DSA, or MRA.
3. Presence of at least one protocol-defined complex high-risk carotid stenosis feature confirmed by carotid ultrasonography, CTA, DSA, HR-VWI, or other protocol-specified imaging modalities.
4. Written informed consent provided by the participant or legally authorized representative.

Exclusion Criteria:

1. Other cerebrovascular lesions that may substantially increase peri-procedural risk or interfere with assessment of the primary outcome, including an untreated ipsilateral intracranial aneurysm >5 mm, cerebral arteriovenous malformation, dural arteriovenous fistula, or other vascular lesions considered to pose significant risk by multidisciplinary assessment.
2. Severe ipsilateral intracranial tandem stenosis ≥70% that is related to a recent ischemic event, is planned for intervention during the study follow-up period, or may interfere with attribution of post-procedural stroke; or complete occlusion of the contralateral internal carotid artery with an unacceptable risk of intolerance to proximal flow arrest.
3. Technical conditions precluding carotid artery stenting or preventing safe implementation of either randomized cerebral protection strategy, including target-vessel occlusion or near-occlusion with distal collapse; free-floating thrombus or high-burden active intraluminal thrombus; absence of an appropriate landing zone for the distal embolic protection device or balloon flow-control segment in the common carotid artery; inability to safely cross, deploy, or retrieve the distal protection device; inability to safely and stably position the balloon guide catheter; severe aortic arch, supra-aortic, carotid-origin, or iliofemoral disease resulting in unacceptable transfemoral access risk; severe vascular tortuosity, angulation, or calcification resulting in unacceptable device-passage, vascular-injury, or stent-deployment risk; unacceptable risk of intolerance to proximal flow arrest; or any other condition preventing safe implementation of either randomized strategy.
4. Previous stenting, angioplasty, or other endovascular mechanical treatment of the target carotid artery; or carotid lesions not prespecified for inclusion in the etiologic complex-lesion cohort, including carotid dissection, vasculitis, traumatic or infectious lesions, pseudoaneurysm, or fibromuscular dysplasia other than carotid web.
5. Modified Rankin Scale (mRS) score ≥3 after a recent stroke, or the presence of a large cerebral infarction, significant cerebral edema or mass effect, hemorrhagic transformation, impaired consciousness, progressive neurological deficits, or clinically unstable neurological status.
6. Contraindication to contrast agents, antiplatelet therapy, anticoagulant therapy, or medications required during the procedure that cannot be adequately managed; or inability or expected inability to receive or complete protocol-required dual antiplatelet therapy.
7. A recent ischemic event considered primarily cardioembolic, or the presence of a high-risk cardiac source of embolism such as left atrial or left ventricular thrombus, infective endocarditis, a mechanical heart valve with inadequate anticoagulation, or an intracardiac mass. Atrial fibrillation alone is not an absolute exclusion criterion unless it is considered the primary cause of the qualifying ischemic event or required anticoagulation cannot be safely combined with the protocol-required antiplatelet regimen.
8. A serious medical condition precluding elective carotid artery stenting, including active bleeding, uncorrectable coagulopathy, severe renal dysfunction without adequate risk-control measures, persistent uncontrolled severe hypertension, active severe infection, myocardial infarction within 6 weeks before screening, unstable acute coronary syndrome, decompensated heart failure, uncontrolled severe arrhythmia, or another serious systemic disease.
9. Contraindication to MRI or anticipated inability to complete the protocol-required baseline and post-procedural MRI/DWI examinations.
10. Current participation, or participation within 3 months before screening, in another clinical study that may affect the study intervention, safety assessment, or primary outcome evaluation; or planned major surgery or endovascular treatment during the peri-procedural period or 30-day follow-up that may interfere with assessment of study outcomes.
11. Inability to understand or comply with study procedures, provide valid informed consent, complete the 30-day clinical follow-up or neurological assessments, or provide reliable primary outcome data; or life expectancy shorter than the required study follow-up period.
12. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study, substantially increases study-related risk, or may compromise the reliability of the study results.