Urgent Carotid Endarterectomy (CEA) Versus Delayed CEA in Symptomatic Carotid Stenosis (SPREAD-STACI II)

NCT ID: NCT06767657

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 456 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2028-01-01

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.

Conditions

Stroke, Ischemic; Transient Ischemic Accident; Endarterectomy, Carotid; Stroke Prevention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group A : Within 72 hours of the ischemic symptom

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:

GROUP A : Within 72 hours of the ischemic symptom. GROUP B: 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.

Group Type: EXPERIMENTAL

CEA (carotid endarterectomy)

Intervention Type: PROCEDURE

Intervention (CEA) is associated to both arms (group A and B)

Group B: Between 72 hours and 14 days after the ischemic symptom

see above

Group Type: ACTIVE_COMPARATOR

CEA (carotid endarterectomy)

Intervention Type: PROCEDURE

Intervention (CEA) is associated to both arms (group A and B)

Interventions

CEA (carotid endarterectomy)

Intervention (CEA) is associated to both arms (group A and B)

Intervention Type: PROCEDURE

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 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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Italian Society of Vascular and Endovascular Surgery

OTHER

Sponsor Role: lead

Responsible Party

EMILIANO CHISCI

Principal Investigator, Head of Endovascular Aortic UNIT, San Giovanni di Dio Hospital, USL Toscana Centro, Florence, ITALY

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Usl Toscana Centro

Florence, , Italy

Countries

Italy

Central Contacts

EMILIANO CHISCI, MD

Role: CONTACT

e.chisci@gmail.com

+39 3281970637

Facility Contacts

Emiliano Chisci, MD

Role: primary

e.chisci@gmail.com

+39 3281970637

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Other Identifiers

SPREAD STACI TRIAL II

Identifier Type: -

Identifier Source: org_study_id