IntraCranial Atherosclerosis Related Large-vessel Occlusion Treated With Urgent Stenting (ICARUS)

Not Applicable

Recruiting

• Conditions: Stroke; Stroke, Acute Ischemic; Intracranial Atherosclerosis
• Interventions: Procedure: Intracranial stenting; Procedure: Continuation of conventional endovascular therapy (EVT)

• Registration Number: NCT06472336
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

The goal of this international, multi-center, randomized clinical trial is to compare two treatment options, early intracranial stenting and continued stent-retriever or aspiration based endovascular treatment, for stroke patients with a large vessel occlusion, who experienced failure of recanalisation after initial treatment due to intracranial atherosclerosis.

Detailed Description

This clinical tiral focuses on comparing treatment options for patients with an acute ischemic stroke, which is a significant cause of death and disability worldwide. Currently, endovascular treatment (EVT) is the gold standard for the removal of large blood clots in the brain arteries (large vessel occlusion, LVO), but sometimes it fails to reopen blocked blood vessels, especially when caused by an underlying intracranial atherosclerosis (ICAD). When restoring blood flow fails, patients' outcomes are much worse, with more than 70% experiencing severe disability or death.

One potential solution for these cases is intracranial stenting, where a stent is permanently implanted in the affected blood vessel to restore blood flow to the brain. This approach has shown promise in other conditions like myocardial infarction. However, there is an ongoing debate whether the benefits are offset by possibly higher bleeding risk, and current guidelines don't provide clear recommendations on the use of intracranial stenting.

Therefore, this study aims to compare the clinical efficacy and safety of early intracranial stenting versus continued conventional EVT (stent-retriever or aspiration based) in LVO stroke patients who haven't responded to conventional EVT due to ICAD.

The results of this clinical trial will offer high quality clinical evidence to determine whether intracranial stenting provides benefits over conventional EVT for LVO stroke patients experiencing recanalisation failure due to ICAD.

Study Timeline

• Study First Submitted: 2024-06-10
• Study First Submitted QC: 2024-06-24
• Study First Posted: 2024-06-25
• Study Start: 2025-03-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-02
• Primary Completion: 2027-08
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 498

Inclusion Criteria

• A relevant clinical deficit defined as a National Institute of Health Stoke Scale (NIHSS) Score of ≥ 6 points for anterior circulation stroke and a NIHSS Score of ≥ 10 for posterior circulation stroke
• Patients presenting within 24 hours of last seen well to the treating hospital
• Occlusion of the Internal Carotid Artery, the M1 segment, the proximal/dominant M2 segment of the Middle Cerebral Artery, the Basilar Artery or the V4 segment of the Vertebral Artery
• Absence of recanalization (thrombolysis in myocardial infarction score of 0 or 1) after up to three endovascular treatment passes
• High probability of underlying intracranial atherosclerotic disease based on the assessment of the treating physician
• Age ≥ 18 years
• Occluded artery amendable to stenting by judgement of the treating physician
• Absence of a large infarct core defined as (posterior circulation) Alberta Stroke Program Early CT Score of 6 or above
• Informed Consent as documented by signature or fulfilling the criteria for emergency consent procedures

Exclusion Criteria

• Acute intracranial haemorrhage
• Pre-stroke modified Rankin Scale score of 2 or above
• Known, severe comorbidities, which will likely prevent improvement or follow-up (cancer, alcohol/drug abuse or dementia)
• Known clotting disease or suspicion of underlying disease which might lead to a hyper coagulant state
• In-hospital Stroke
• Known contraindications for anti-platelet therapy
• Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals or their alloys
• Foreseeable difficulties in follow-up due to geographic reasons (e.g., patients living abroad)
• Evidence of an ongoing pregnancy prior to randomization
• Radiological confirmed evidence of mass effect or intracranial tumour (except small meningioma)
• Radiological confirmed evidence of cerebral vasculitis
• Evidence of vessel recanalization prior to randomisation
• Participation in another interventional trial which could confound the primary endpoint

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Intracranial stenting	In patients within the intervention group, the treating physician attempts to perform intracranial stenting (with or without balloon dilation).
Control group	Continuation of conventional endovascular therapy (EVT)	In patients within the control group, the treating physician does not perform intracranial stenting and/or balloon dilation. Conventional endovascular therapy will be continued.

Primary Outcome Measures

Name	Time	Method
Assessment whether intracranial stenting compared to conventional endovascular treatment is beneficial regarding patient's functional status	90 days post randomization	To evaluate whether intracranial stenting compared to conventional endovascular treatment is beneficial, the degree of disability and dependency in everyday life is measured with the modified Rankin Scale (mRS), which is a standard tool to assess the neurological outcome in trials with acute severe brain disease. The mRS ranges from 0 (no disability) to 6 (death). Lower values indicate less disability.; The assessment of mRS is performed by an independent and blinded person that is certified for scoring the mRS.

Secondary Outcome Measures

Name	Time	Method
Assessment of the quality of life	90 and 365 days post randomization	To assess the quality of life, the standardized questionnaire, EuroQol-5d, is used at 90 and 365 days after randomization. At 365 days the assessment is conduct as a telephone interview.
Assessment of the residential status	365 days post randomization	To assess the patient's residential status, a telephone interview with the patient or if not available his next of kin/caregiver is performed 365 days after the randomization.
Assessment of disability and dependency in everyday live activities	365 days post randomization	To assess the functional outcome, the modified Rankin Scale (mRS) is measured after 365 days via a telephone interview. The mRS ranges from 0 (no disability) to 6 (death). Lower values indicate less disability.
Symptomatic intracranial haemorrhage (sICH)	0-24 hours post randomization	The incidence of Symptomatic intracranial haemorrhage (sICH) is assessed based on the modified Safe Implementation of Treatments in Stroke-Monitoring Study (SITS-MOST) criteria. The SITS-MOST criteria define sICH as a parenchymal hematoma grade 1 or 2, indicated by an increase of at least 4 points on the National institute of Health Stroke Scale (NIHSS) (compared to the lowest recorded NIHSS post randomization). sICH is the main safety outcome in most stroke trials.
Percentage of penumbral tissue saved (imaging based outcome parameter)	0 - 24 hours post randomization	Percentage of penumbral tissue saved, which is defined as the proportion of tissue at risk at baseline that did not progress to infarction at 24 hours after randomization.
Assessment of the cognitive function	90 days post randomization	To assess the cognitive function, the validated Montreal Cognitive Assessment (MoCA) is used at the follow-up visit 90 days after randomization. If the patient cannot perform the test or is deceased, his/her score is rated as minimal.; Scores range from 0 to 30 with higher scores indicating better cognitive function. A score of 26 or above indicates normal cognitive function.
Grading of recanalization at 24 hours after the randomization (imaging based outcome parameter)	24 hours post randomization	The arterial occlusion lesion scale will be used to grade the vessel status at 24 hours after randomization on a CT-angiography or MR-angiography (if done according to local standards of care). It ranges from 0 to 3 with 0 indicating no recanalization and 3 complete recanalization.
Assessment of the discharge location	90 days post randomization	The discharge location is assessed at the follow-up visit 90 days after randomization. Discharge location could either be: (a) other hospital, (b) rehabilitation facility, (c) nursing home, (d) residential home or (e) own household.
Change in the National Institutes of Health Stroke Scale (NIHSS) score	Baseline, 24 hours, 5-7 days and, optionally, 90 days post randomization	To compare the impact of the two treatment options on the neurological deficit of the patient, the change in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and post randomization is evaluated. The NIHSS is a standard tool to assess the severity of stroke symptoms.; The NIHSS ranges from 0 to 42 with less values indicating less neurological deficit.
Grading of reperfusion at the end of the intervention (imaging based outcome parameter)	0 - 60 minutes post randomization	The modified Thrombolysis In Cerebral Infarction (mTICI) score will be used to grade the reperfusion success at the end of the procedure. mTICI ranges from 0 (no reperfusion) to 3 (full reperfusion)

Trial Locations

Locations (1)

University Hospital Basel, Department of Interventional and Diagnostical Neuroradiology; 🇨🇭 Basel, BS, Switzerland