Clinical trial NCT06767657: Urgent Carotid Endarterectomy (CEA) Versus Delayed CEA in Symptomatic Carotid Stenosis (SPREAD-STACI II)
Official title: Multicenter, Open-label Randomized Study Comparing Urgent Carotid Endarterectomy (CEA) (within 72 Hours) Versus Delayed CEA (after 72 Hours) in Patients with Symptomatic Carotid Stenosis (SPREAD-STACI II)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke, Ischemic
Transient Ischemic Accident
Endarterectomy, Carotid
Stroke Prevention
Keywords: stroke
endarterectomy
transient ischemic accident
stroke prevention
Lead sponsor: Italian Society of Vascular and Endovascular Surgery
Sponsor class: OTHER
First posted: 2025-01-10
Enrollment: 456
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will evaluate the same surgical procedure, carotid endarterectomy (CEA), which involves the removal of the atherosclerotic plaque causing thromboembolism or hemodynamically significant stenosis. This will be performed in two different timeframes:

Within 72 hours of the ischemic symptom. Between 72 hours and 14 days after the symptom.

The two study groups will not differ in the type of treatment offered but only in the timing of its execution.

No experimental procedures will be conducted. Whether CEA is performed within 72 hours or after this period, the surgical procedure will adhere fully to the current guidelines.
Primary purpose: TREATMENT

Brief summary: In patients with internal carotid artery (ICA) stenosis of 50% or greater (measured according to the criteria of the North American Symptomatic Carotid Endarterectomy Trial (NASCET)) who have experienced a transient ischemic attack (TIA) or minor ipsilateral stroke, carotid endarterectomy (CEA) offers maximum benefit if performed within 15 days of the initial ischemic symptom. National and international guidelines recommend surgical treatment (CEA) within this timeframe; however, no studies have specifically evaluated the optimal timing for CEA after a TIA or minor stroke.

It is well established that the risk of a major stroke is highest in the first few days following a transient ischemic attack or minor stroke and then decreases over the subsequent days and weeks.

This raises the hypothesis that performing an urgent carotid endarterectomy (within 3 days) may provide greater benefit compared to a delayed procedure (between 4 and 15 days).

Detailed description: Background and Rationale

In patients with internal carotid artery (ICA) stenosis of 50% or greater (measured according to the criteria of the North American Symptomatic Carotid Endarterectomy Trial (NASCET)) who have experienced a transient ischemic attack (TIA) or minor ipsilateral stroke, carotid endarterectomy (CEA) offers maximum benefit if performed within 15 days of the initial ischemic symptom. National and international guidelines recommend surgical treatment (CEA) within this timeframe; however, no studies have specifically evaluated the optimal timing for CEA after TIA or minor stroke.

It is well established that the risk of a major stroke is highest in the first few days following a transient ischemic attack or minor stroke and then decreases over the subsequent days and weeks. This raises the hypothesis that performing an urgent carotid endarterectomy (within 3 days) may provide greater benefit compared to a delayed procedure (between 4 and 15 days).

Study Objectives

Primary Endpoint

To demonstrate that CEA for symptomatic ICA stenosis of 50% or greater (NASCET criteria) performed urgently within 72 hours of the onset of the ischemic symptom (TIA or minor stroke) is more effective than delayed CEA (performed after 72 hours but within 15 days) in reducing the risk of death, any type of stroke, and myocardial infarction within 90 days of the ischemic event.

Secondary Endpoints

To demonstrate that urgent CEA (within 72 hours of symptom onset) is more effective than delayed CEA (after 72 hours but within 15 days) in reducing the risk of ipsilateral ischemic stroke within 90 days of the ischemic event.

To identify potential subgroups of patients who benefit more from urgent CEA compared to delayed CEA.

To demonstrate that urgent CEA (within 72 hours) is as safe as delayed CEA (after 72 hours) in terms of the risk of cerebral hemorrhagic complications.

Study Design

This is a prospective, randomized, multicenter, controlled, non-profit interventional study with blinded follow-up at 90 days by the neurologist/internist investigator. The study is coordinated by the Vascular Surgery Unit (UOC) at San Giovanni di Dio Hospital, USL TOSCANA CENTRO, in collaboration with the Vascular Surgery Units listed above. All patients treated at the participating centers are eligible for inclusion if they meet the inclusion and exclusion criteria and provide informed consent to participate in the study.

The study does not introduce modifications or conflicts with standard clinical practice, as all enrolled and randomized patients (whether within or after 72 hours) will undergo surgical treatment (CEA) within 15 days of the index symptom, in accordance with national and international guidelines.

Study Population

Number of patients to be enrolled: 456

Withdrawal Criteria Patients may withdraw from the study at any time.

Interventions

The study will evaluate the same surgical procedure, carotid endarterectomy (CEA), which involves the removal of the atherosclerotic plaque causing thromboembolism or hemodynamically significant stenosis. This will be performed in two different timeframes:

Within 72 hours of the ischemic symptom. Between 72 hours and 14 days after the symptom.

The two study groups will not differ in the type of treatment offered but only in the timing of its execution.

No experimental procedures will be conducted. Whether CEA is performed within 72 hours or after this period, the surgical procedure will adhere fully to the current guidelines.

Assessment of Potential Benefit/Risk for the Study Population

The morbidity and mortality risk for the study participants is expected to be within the 6% limit for stroke/mortality at 30 days, as defined by the safety threshold in the literature and by national and international guidelines.

If this threshold (stroke/mortality at 30 days ≥ 6%) is exceeded in either group, the study will be terminated for safety reasons.

Eligibility criteria: Eligibility Criteria

Inclusion Criteria:

Patients presenting with the following characteristics:

De novo stenosis of the carotid bifurcation and/or internal carotid artery origin, equal to or greater than 50% (NASCET method), diagnosed by color Doppler ultrasound, MR angiography (MRA), CT angiography (CTA), or catheter angiography.

TIA or minor ischemic stroke (NIHSS ≤ 5) ipsilateral to the carotid stenosis, occurring within the previous 24 hours.

Preserved consciousness and neurologically stable symptoms. No evidence of ongoing cerebral ischemia, or evidence of cerebral ischemia with a diameter \<25 mm.

Age between 45 and 90 years. ASA score \< 4. Ability to comply with follow-up requirements as specified. Willingness to provide informed consent for participation in the study.

A patient with an NIHSS ≤ 5 who is aphasic may be unable to provide consent. In these cases:

The attending physician assesses the feasibility of including the patient. Family members are informed but, under Italian law, cannot provide consent. A third-party physician certifies that the patient meets the inclusion criteria.

The attending physician signs the appropriate form, and randomization proceeds. If and when the patient regains the ability to provide or refuse consent, the informed consent form will be presented to them. Should they decline, their data will be removed from the study database.

Additionally, the study includes patients who underwent thrombolysis and/or mechanical thrombectomy after the onset of the index symptom, followed by a brain CT/MRI without secondary cerebral hemorrhage (PH1, PH2, or PHr).

Exclusion Criteria:

Stenosis \< 50% (NASCET method) at the bifurcation and/or internal carotid artery origin, diagnosed by ECD, CTA, or MRA.

Carotid thrombosis or dissection. NIHSS \> 5. Cerebral hemorrhage. Impaired consciousness or neurologically unstable condition. Cancer, any condition with a poor prognosis, major cardiopathy, or any severe neurological disorder.

CT or MRI evidence of cerebral ischemia \> 25 mm in diameter. CT or MRI evidence of cerebral lesions of uncertain origin. Recurrent TIA or stroke-in-evolution. Age \< 45 years or \> 90 years. ASA risk score = 4. Lack of informed consent. Inability to undergo CEA within 72 hours of the initial ischemic symptom. Inability to participate in a 90-day follow-up after the initial ischemic symptom.

Previous CEA or stenting of the examined carotid artery.

Primary outcomes:
measure: Number of participants with treatment-related death, any type of stroke, and myocardial infarction events as assessed by CTCAE v4.0
timeFrame: From enrollment to 90 days follow-up from CEA
Secondary outcomes:
measure: Number of participants with treatment-related ipsilateral ischemic stroke events as assessed by CTCAE v4.0
timeFrame: From enrollment to 90 days follow-up from CEA
measure: Number of participants with treatment-related cerebral hemorrhagic events as assessed by CTCAE v4.0
timeFrame: From enrollment to 90 days follow-up from CEA
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Usl Toscana Centro
Study officials:
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