Carotid Artery Stenting During Endovascular Treatment of Acute Stroke (CASES)

Carotid Artery Stenting During Endovascular Treatment of Acute Ischemic Stroke: A Randomized Multicenter Clinical Trial in Patients With Acute Ischemic Stroke and Carotid Artery Stenosis Undergoing Endovascular Treatment

Rationale: Approximately 20% of the patients with acute ischemic stroke due to an intracranial large vessel occlusion (LVO) has a high-grade stenosis in the ipsilateral cervical carotid artery. It is uncertain whether immediate carotid artery stenting (CAS) of a cervical carotid artery stenosis during endovascular thrombectomy (EVT) is beneficial. Immediate CAS could improve cerebral perfusion and prevent recurrent ischemic stroke but could also increase the chance of intracranial hemorrhagic complications due to hyperperfusion syndrome or to the required antiplatelet treatment to prevent stent occlusion. Moreover, some patients end up with a severe disabling stroke after EVT. In these patients carotid revascularization by carotid endarterectomy (CEA) or CAS would usually not be performed but these patients would be treated by medical management only.

Objective: to assess the safety and efficacy of immediate cervical CAS during EVT in patients with acute ischemic stroke due to LVO with a high-grade stenosis >50% or occlusion of the ipsilateral cervical carotid artery.

Study design: prospective randomized open label controlled trial comparing immediate CAS during EVT versus EVT with deferred treatment of the cervical carotid artery lesion (deferred CAS/CEA or medical management alone). Outcome assessment will be blinded for treatment allocation.

Study Overview

• Status: Recruiting
• Conditions: Carotid Stenosis; Stroke, Ischemic; Stroke, Acute; Carotid Atherosclerosis; Carotid Occlusion
• Intervention / Treatment: Procedure: carotid artery stenting during EVT; Other: no carotid artery stenting during EVT

Detailed Description

Background and study aims A stroke is a serious life-threatening medical condition that happens when the blood supply to part of the brain is cut off. Approximately 1 in 5 patients suffering stroke have a narrowed carotid artery. It is not yet known if early treatment to insert a tube (stent) into the narrowed artery to hold it open and prevent future stroke is worth the difficulties associated with such treatment.

Who can participate? Patients with acute ischemic stroke with a CT-angiography-proven intracranial LVO in the anterior circulation (ICA, A1, M1 or M2) as well as an ipsilateral cervical carotid artery tandem lesion of presumed atherosclerotic origin with a stenosis >50% or an ipsilateral acute proximal internal carotid artery occlusion who are treated with EVT according to the guidelines.

What does the study involve? Patients will be randomly allocated to receive either a carotid artery stent immediately after suffering a stroke, or to treatment as usual.

What are the possible benefits and risks of participating? Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients are being treated with EVT according to the local guidelines. The patients allocated to the intervention group will undergo CAS during EVT, which carries a risk of cerebral hyperperfusion syndrome and subsequent intracerebral hemorrhage. The potential benefits of immediate CAS during thrombectomy include: an improvement of cerebral blood flow during and after EVT. A second benefit is a lower risk of recurrent stroke in the first 14 days compared to the deferred treatment strategy. A third benefit of immediate CAS is that the patient does not need a second invasive treatment (carotid revascularization surgery (CEA or CAS) during the rehabilitation period which again carries some risk of complications. At last, the immediate CAS approach is likely to reduce health care costs.

Where is the study run from? The study will be coordinated by the University Medical Center Groningen in the Netherlands and by the University Hospital Leuven in Belgium. 26 centres (9 in Belgium and 17 in the Netherlands) will participate.

When is the study starting and how long is it expected to run for? November 2022 to November 2026

Who is funding the study? The study is part of the COllaboration of New TReatments of Acute STroke (CONTRAST) consortium (www.contrast-consortium.nl).

The study is funded by the BeNeFIT funding members (ZonMw/KCE) (the Netherlands)

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Maarten Uyttenboogaart, MD PhD; Phone Number: +31 50 3612400; Email: m.uyttenboogaart@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: Maarten Uyttenboogaart, MD PhD; Email: m.uyttenboogaart@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Acute ischemic stroke due to proximal intracranial occlusion in the anterior circulation (intracranial ICA, M1, proximal M2) on the CT angiography
2. Stenosis >50% according to the NASCET criteria16 or initial occlusion of the ipsilateral cervical carotid artery of presumed atherosclerotic origin on baseline CT angiography
3. Eligible for EVT according to the guidelines: EVT within 6 hours of onset or EVT between 6-24 hours after onset based on perfusion CT imaging selection (conform current guidelines)
4. Baseline National Institute of Health Stroke Scale (NIHSS) score ≥2
5. Age >18 years
6. Written informed consent (deferred consent)

Exclusion Criteria:

1. Any intracranial hemorrhage
2. Cervical carotid artery stenosis or occlusion with other causes than presumed atherosclerosis (e.g. carotid artery dissection, floating thrombus, carotid web)
3. Any exclusion criterion for EVT according to the guidelines
4. Pre stroke disability (defined as a modified Rankin Scale score >2)
5. Recent gastro-intestinal or urinary tract hemorrhage (<6 weeks)
6. Recent severe head trauma (<6 weeks)
7. Recent infarction on baseline brain CT in the same vascular territory (<6 weeks)
8. Known allergy to aspirin and/or clopidogrel
9. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carotid artery stenting during endovascular thrombectomy; In the intervention group, the cervical carotid artery lesion will be treated with a stent during the EVT (just before or directly after intracranial thrombus removal)	Procedure: carotid artery stenting during EVT; Patients with an ipsilateral high grade carotid artery stenosis or occlusion of presumed atherosclerotic origin and an proximal intracranial large vessel occlusion in the anterior circulation will be randomized using a web-based randomization tool to immediate carotid artery stenting or deferred treatment strategy of carotid artery stenosis. In the intervention group, the cervical carotid artery lesion will be treated with a stent during the EVT (just before or directly after intracranial thrombus removal), the control group will be treated according to the national guidelines with carotid endarterectomy of carotid artery stenting (for patients with non-disabling stroke) or medical management alone (for patients with severe disabling stroke).
Active Comparator: No immediate carotid artery stenting during endovascular thrombectomy; The control group will be treated according to the national guidelines with carotid endarterectomy of carotid artery stenting (for patients with non-disabling stroke) or medical management alone (for patients with severe disabling stroke)	Other: no carotid artery stenting during EVT; A deferred treatment approach: carotid revascularization within two weeks after stroke onset or best medical management only, depending on the functional recovery of the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale score	Stroke-related disability measured using the Modified Rankin Scale (mRS) Score at 90 days after stroke onset.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality	90 days
NIHSS score 24 hours	Stroke severity	24 hours
TICI score	Recanalization after EVT	during EVT
Final infarct volume on brain CT scan at 24 hours	Final infarct volume on brain CT scan at 24 hours	24 hours
Arterial occlusive lesion score at 24 hours	Arterial occlusive lesion score at 24 hours	24 hours
Any stroke	Any ischemic, hemorrhagic stroke or TIA	90 days
Recurrent ipsilateral TIA/ischemic stroke	Recurrent ipsilateral TIA/ischemic stroke	90 days
Carotid re-occlusion	Carotid re-occlusion on CTA at 24 hours or duplex at 90 days	24 hours and 90 days
Quality of Life	Quality of life measured with the EQ5D-5L)	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic Intracranial hemorrhage	Symptomatic Intracranial hemorrhage	24 hours and 90 days
Any intracranial hemorrhage	Any intracranial hemorrhage	24 hours and 90 days

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Maarten Uyttenboogaart, MD PhD, University Medical Center Groningen

Publications and helpful links

Helpful Links

• trial website
• Contrast Consortium

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Estimated): April 5, 2026
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: July 15, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Stroke; Ischemic Stroke; Ischemia; Carotid Stenosis; Carotid Artery Diseases; Constriction, Pathologic; Atherosclerosis
• Other Study ID Numbers: NL79046.078.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.contrast-consortium.nl/wp-content/uploads/2021/03/SOP-publications-v1.0.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No