Carotid Artery Stenting for Stroke

(EASI-TOC Trial)

Overseen By Alexandre Y Poppe, MD CM

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Antiplatelet therapy

Disqualifiers: Neurological impairment, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate procedure

458 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a known contra-indication to antiplatelet therapy, you may not be eligible to participate.

What data supports the effectiveness of the treatment Carotid Artery Stenting for Stroke?

Carotid artery stenting (CAS) is considered a valuable option for patients at high risk for traditional surgery, offering a less invasive alternative to carotid endarterectomy (CEA). However, the effectiveness of CAS compared to CEA in preventing stroke and death is still uncertain, and further studies are needed to confirm its long-term benefits. ^{1 2 3 4 5}

Is carotid artery stenting generally safe for humans?

Carotid artery stenting (CAS) is considered a relatively safe and less invasive treatment for certain conditions, but it does carry risks such as cerebral thromboembolic events (blockages in the brain's blood vessels) and higher complication rates compared to other procedures. However, studies have shown that with the right devices and techniques, the safety of CAS can be improved. ^{6 7 8 9 10}

How is carotid artery stenting different from other treatments for stroke prevention?

Carotid artery stenting (CAS) is a minimally invasive procedure that serves as an alternative to carotid endarterectomy (CEA), which is a more invasive surgical option. CAS involves placing a stent (a small mesh tube) in the carotid artery to keep it open, and it can be performed through different access points, such as the femoral or radial artery, offering flexibility in approach. ^{1 11 12 13 14}

What is the purpose of this trial?

Patients with tandem occlusion or tandem lesion (TL), that is, stroke with an acute intracranial anterior circulation occlusion and an ipsilateral cervical ICA (c-ICA) high-grade stenosis or occlusion, constitute about 15-20% of patients undergoing endovascular thrombectomy (EVT). However, the optimal treatment of acute stroke patients with TL remains uncertain, as relatively few patients with TL were included in the major randomized controlled trials of EVT and management of the c-ICA was generally not specified by protocol nor analyzed post-hoc. Recent large multi-centre retrospective cases series suggest that acutely stented patients may have more favorable outcomes than patients treated with angioplasty alone or those with no acute ICA intervention, but high quality randomized trial data are lacking. EASI-TOC, a phase 3, academic multi-centre, controlled trial (PROBE design) with embedded pilot phase, will seek to determine if in patients undergoing acute intracranial thrombectomy for anterior circulation stroke with concurrent ipsilateral symptomatic high-grade (≥70%) atherosclerotic stenosis or occlusion of the extracranial ICA, endovascular ICA revascularization with stenting is superior to intracranial thrombectomy alone with regards to functional outcome at 90 days. Patients will be randomized to Acute stenting or No acute stenting (1:1 allocation).

Research Team

Alexandre Y Poppe, MD CM

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for stroke patients with a specific blockage in the neck arteries (carotid artery disease) and an additional clot in the brain, who can get to the hospital within 24 hours of symptoms starting. They must be able to give consent and have a chance of recovery with treatment. Pregnant individuals, those unlikely to follow the study plan or attend follow-up, or with certain pre-existing conditions are excluded.

Inclusion Criteria

You have a serious problem with your nerves that affects your daily life, as determined by you or your doctor.

I had a stroke and qualify for a clot removal procedure.

Informed consent from patient or surrogate or deferral of consent, according to local ethics policies

Exclusion Criteria

My neck artery is not severely narrowed or blocked, as confirmed by a specific imaging test.

You have a pre-existing neurological condition that affects your daily life.

I have a blockage in my neck artery but not in my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo acute intracranial thrombectomy with or without ICA stenting

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Regular follow-up visits as per protocol

Long-term Follow-up

Participants are monitored for long-term outcomes and any recurrent stroke or retinal ischemia

1 year

Follow-up visits and assessments

Treatment Details

Interventions

• Antiplatelet Agents
• Carotid artery stenting

Trial Overview The EASI-TOC trial is testing if adding stenting (a procedure to keep arteries open) of the carotid artery improves recovery from stroke compared to just removing the brain clot without stenting. Participants will be randomly assigned either acute stenting plus clot removal or only clot removal.

Participant Groups

Group I: Acute Stenting Active Control 2 Interventions

All patients in this arm will receive standard of care with regards to intracranial thrombectomy and use of intravenous thrombolysis. In this arm, the cervical carotid artery stenosis will be revascularized with a stent during the acute thrombectomy procedure.

Group II: No Acute Stenting Active Control 1 Intervention

All patients in this arm will receive standard of care with regards to intracranial thrombectomy and use of intravenous thrombolysis. In this arm, the cervical carotid artery stenosis will be not revascularized with a stent during the acute thrombectomy procedure.

Carotid artery stenting is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Carotid artery stenting for:

• Symptomatic carotid stenosis
• Asymptomatic carotid stenosis

Approved in United States as Carotid artery stenting for:

• Symptomatic carotid stenosis
• High-risk asymptomatic carotid stenosis

Approved in Canada as Carotid artery stenting for:

• Symptomatic carotid stenosis
• Asymptomatic carotid stenosis

Approved in Japan as Carotid artery stenting for:

• Symptomatic carotid stenosis

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Health Sciences North Research Institute

Collaborator

Trials

11

Recruited

2,100+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

Laval University

Collaborator

Trials

439

Recruited

178,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Findings from Research

In a study of 45 patients undergoing carotid artery stenting (CAS) from 2006 to 2018, the procedure showed a low minor stroke rate of 6.6% with no major strokes or deaths, indicating a favorable safety profile for high-risk patients.

The results suggest that CAS can be an effective treatment for carotid artery stenosis, especially in asymptomatic patients, and highlight the importance of centralizing the procedure to experienced interventionalists for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of carotid artery stenting. Lessons learned in a Belgian 'real world' practice. Kerselaers, L., Gallala, S., Aerden, D., et al.[2022]

Carotid artery stenting (CAS) is a promising alternative to carotid endarterectomy (CEA) for high-risk patients, as illustrated by successful treatment of severe recurrent stenosis with a self-expanding stent.

Despite its potential, CAS is still in the early stages of development, and further trials are necessary to establish its long-term efficacy compared to CEA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular treatment of carotid artery stenosis. Cumming, ME., Cumming, MJ.[2016]

In a study of 25 high-risk surgical patients undergoing extracranial carotid artery stenting (CAS), only 2 patients experienced restenosis, indicating a low rate of this complication, particularly when post-stenting angioplasty was selectively applied.

The long-term morbidity and mortality rate was 8.3% for patients followed for at least two years, with no occurrences of serious complications like intracerebral hemorrhages or recurrent strokes, suggesting that CAS is a safe alternative for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracranial carotid artery stenting: the Puerto Rico medical center endovascular neurosurgery service experience. Feliciano, CE., Effio, E., Hernández-Gaitán, MS., et al.[2011]

In a study of 46,784 Medicare beneficiaries, the introduction of carotid arterial stenting (CAS) did not significantly reduce mortality or combined adverse outcomes compared to traditional carotid endarterectomy within 90 and 270 days after the procedure.

Higher adoption rates of CAS in certain localities were linked to increased rates of 90-day and 270-day adverse outcomes, suggesting that while CAS is an alternative treatment, it may carry higher risks in some settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of carotid arterial stenting versus endarterectomy. Groeneveld, PW., Yang, L., Greenhut, A., et al.[2021]

Carotid artery stenting (CAS) can be a safer alternative to carotid endarterectomy for certain patients, but it is important to identify specific anatomical and lesion characteristics that may increase the risk of complications during the procedure.

The paper aims to establish criteria for selecting patients who are most likely to benefit from CAS, highlighting the need for careful patient evaluation to minimize risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence overview: anatomical criteria determining patients at high risk for carotid stenting. VAN DEN Berg, JC.[2017]

In a study of 61 patients undergoing carotid artery stenting (CAS) with embolic protection devices (EPDs), the selection of a proximal-occlusive-type EPD resulted in a low perioperative stroke rate of only 1.6% and no deaths, indicating its safety in high-risk patients.

The study suggests that using a tailored algorithm for EPD selection based on patient symptoms and imaging can effectively reduce major adverse events after CAS, highlighting the importance of personalized approaches in managing carotid artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative ischemic events in patients undergoing carotid artery stenting using algorithmic selection for embolic protection. Kawabata, Y., Nakajima, N., Miyake, H., et al.[2020]

In a study of 224 patients undergoing carotid angioplasty and stenting (CAS), octogenarians (patients aged 80 and above) did not experience a higher risk of adverse events compared to younger patients, indicating that age alone should not exclude patients from this procedure.

Both groups had similar procedural success rates and hospital stays, with low rates of transient ischemic attacks and strokes, suggesting that CAS is a safe option for older patients when performed under appropriate conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Octogenarians are not at increased risk for periprocedural stroke following carotid artery stenting. Bacharach, JM., Slovut, DP., Ricotta, J., et al.[2016]

In a 9-year study involving 2,124 patients undergoing carotid artery stenting (CAS), the researchers developed the Siena CAS risk score to predict the 30-day risk of stroke based on various patient and procedural factors.

The Siena CAS score categorizes patients into low, medium, and high-risk groups for stroke, showing a sensitivity of 82% and specificity of 79%, but requires further validation before clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siena carotid artery stenting score: a risk modelling study for individual patients. Setacci, C., Chisci, E., Setacci, F., et al.[2022]

Carotid artery stenting (CAS) is generally considered a safe treatment for internal carotid artery stenosis, but acute stent thrombosis can occur, posing serious risks, as demonstrated in a case involving a 79-year-old man who experienced this complication shortly after the procedure.

The successful management of acute stent thrombosis through a combination of thrombolysis and balloon postdilation highlights the importance of prompt intervention and suggests that mechanical approaches can effectively address complications when stents do not fully adhere to the blood vessel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute In-Stent Thrombosis after Carotid Angioplasty and Stenting: A Case Report and Literature Review. Hu, W., Wang, L., Wang, G.[2022]

Carotid artery stenting (CAS) has shown a low 30-day mortality rate of 0.9% and a stroke rate of 3-4% in recent case series, indicating improved safety compared to earlier studies.

Advancements in device technology and operator skills have led to a decrease in complication rates for CAS, suggesting that current outcomes may be better than those reported in older studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systematic review of complications for proper informed consent (9) periprocedural complications of carotid artery stenting: a review article]. Asai, T., Miyachi, S., Izumi, T., et al.[2018]

In a study comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA) involving 94 patients (46 CAS and 48 CEA), both procedures showed similar rates of critical restenosis, stroke, and re-interventions over an average follow-up of 13 months.

The results suggest that CAS, when performed with neuroprotection devices, has comparable safety and efficacy to CEA, indicating it can be a viable alternative for treating carotid occlusive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follow-up results of carotid angioplasty with stenting as assessed by duplex ultrasound surveillance. Park, B., Aiello, F., Dahn, M., et al.[2016]

Transradial carotid artery stenting (CAS) was successfully performed in 20 patients without any major complications, demonstrating its effectiveness as an alternative to the traditional transfemoral approach.

While the procedural and fluoroscopy times were slightly longer for transradial CAS compared to transfemoral CAS, the differences were minimal, suggesting that this technique can be a viable option for experienced operators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stenting the carotid artery from radial access using a Simmons guide catheter. Heck, D., Jost, A., Howard, G.[2022]

In a study of 10,958 Medicare patients aged 66 and older, carotid artery stenting (CAS) showed similar in-hospital and 1-year stroke rates compared to carotid endarterectomy (CEA), indicating comparable efficacy in preventing strokes.

However, CAS patients experienced significantly higher all-cause mortality at 1 year (9.9% for CAS vs. 6.1% for CEA), which may be attributed to their higher baseline risk factors, such as existing coronary and peripheral arterial disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes after carotid artery stenting and endarterectomy in the Medicare population. Wang, FW., Esterbrooks, D., Kuo, YF., et al.[2018]

In a study of 96 patients undergoing carotid artery stenting (CAS), those with open-cell stents experienced significantly more new lesions on postprocedural imaging compared to those with closed-cell stents (24 vs 12 lesions).

While the overall 30-day clinical outcomes were similar between the two stent types, stent design was identified as a strong risk factor for new embolism, suggesting that choosing the right stent could enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of embolism associated with carotid artery stenting: open-cell versus closed-cell stents. Park, KY., Kim, DI., Kim, BM., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Results of carotid artery stenting. Lessons learned in a Belgian 'real world' practice. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Endovascular treatment of carotid artery stenosis. [2016]

3. Puerto Rico pubmed.ncbi.nlm.nih.gov

Extracranial carotid artery stenting: the Puerto Rico medical center endovascular neurosurgery service experience. [2011]

4. United States pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of carotid arterial stenting versus endarterectomy. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

Evidence overview: anatomical criteria determining patients at high risk for carotid stenting. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Postoperative ischemic events in patients undergoing carotid artery stenting using algorithmic selection for embolic protection. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Octogenarians are not at increased risk for periprocedural stroke following carotid artery stenting. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Siena carotid artery stenting score: a risk modelling study for individual patients. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Acute In-Stent Thrombosis after Carotid Angioplasty and Stenting: A Case Report and Literature Review. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Systematic review of complications for proper informed consent (9) periprocedural complications of carotid artery stenting: a review article]. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Follow-up results of carotid angioplasty with stenting as assessed by duplex ultrasound surveillance. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Stenting the carotid artery from radial access using a Simmons guide catheter. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Outcomes after carotid artery stenting and endarterectomy in the Medicare population. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Incidence of embolism associated with carotid artery stenting: open-cell versus closed-cell stents. [2022]