SELECT2: A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke

University Hospitals Cleveland Medical Center352 enrolled

Overview

SELECT 2 evaluates the efficacy and safety of endovascular thrombectomy compared to medical management alone in acute ischemic stroke patients due to a large vessel occlusion in the distal ICA and MCA M1 who have large core on either CT (ASPECTS: 3-5) or advanced perfusion imaging (\[rCBF\<30%\] on CTP or \[ADC\<620\] on MRI: ≥50cc) or both and are treated within 0-24 hours from last known well.

SELECT 2 is a prospective, phase III randomized, international, multicenter, assessor-blinded controlled trial evaluating the efficacy and safety of thrombectomy in patients with large core on either CT or advanced perfusion imaging treated within 0-24 hours from last known well. Patients with the final diagnosis of an acute ischemic stroke due to a large vessel occlusion in the distal ICA and MCA M1 who have large core on either CT (ASPECTS: 3-5) or advanced perfusion imaging (\[rCBF\<30%\] on CTP or \[ADC\<620\] on MRI: ≥50cc) or both within 0-24 hrs from last known well will be randomized in a 1:1 ratio into thrombectomy plus medical management vs medical management alone. Patient outcomes will be measured at baseline, 24 hours post, discharge, 30 days and 90 days. The primary endpoint is the Modified Rankin Scale (mRS) at 90 (+/- 15) days. The primary outcome is a shift on 90-day mRS. Secondary outcomes are favorable clinical outcomes: mRS score of 0-2, safety outcomes such the incidence of symptomatic intracranial hemorrhage (sICH per SITS-MOST) and Imaging endpoints such as infarct volume on MRI diffusion-weighted imaging (DWI) sequence (or CT if MRI not feasible) 24 to 72 hours after randomization. CT images will be read by iSchemaView automated ASPECTS as well as by a physician. In cases where there is disagreement, the physician reading will override the automated software reading. CT/MR perfusion images with mismatch determination will be read by iSchemaView automated RAPID software. All the images will be adjudicated by a blinded core lab at the University of Texas-Medical School at Houston. A maximum of 560 patients will be randomized across the study sites. Covariate adaptive randomization will be used to balance the distribution of important variables. Interim analyses will be conducted at 200 and 380 patients, at which time the study may stop for efficacy or futility.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Conditions

Acute Ischemic Stroke

Interventions

Endovascular ThrombectomyDEVICE

Patients randomized to endovascular thrombectomy arm will receive thrombectomy plus medical management. They will be treated with thrombectomy devices (stent-retrievers or aspiration devices) currently cleared by the FDA for thrombus removal in patients experiencing an acute stroke within 24 hours of symptom onset. The devices which will be used are FDA-approved stent retrievers: the Trevo Retriever, the Solitaire Revascularization Device, EmboTrap Revascularization Device and Tigertriever Revascularization Device; and/or the aspiration devices approved by the FDA (e.g. MicroVention SOFIA Catheter, and the Penumbra thrombectomy system). The choice of thrombectomy method, primary approach/technique, whether primary aspiration or primary stent-retriever with or without aspiration, will be left up to the interventionalist, with any of the FDA-approved devices approved in the study protocol or a combination of them.

Medical ManagementOTHER

Patients will receive standard AHA guideline-directed medical therapy, which will include IV thrombolytic therapy available for use according to practice guidelines in patients presenting within the first 3 hours from last-seen-normal and meeting other FDA label criteria, or up to 4.5 hours from last-seen-normal and meeting other AHA guidelines. For non-thrombolysis treated patients, this will include aspirin 325 mg on day 1 followed by aspirin 81 mg or 325 mg thereafter, which will be determined by treating physician and standard deep venous thrombosis prevention therapy. Intravenous anticoagulation and dual anti-platelet therapy will be discouraged without clear documented reasoning. Post-thrombolysis patients will be treated based on standard study site protocols for these patients.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adults (18-85 years) with the final diagnosis of an acute ischemic stroke 2. NIH Stroke Scale Score (NIHSS) ≥ 6 3. Last known well to groin puncture or medical management between 0 to 24 hours 4. Pre-stroke modified Rankin Scale score (mRS) of 0-1 5. Eligible for thrombectomy or medical management 6. Signed Informed Consent obtained 7. Subject willing to comply with the protocol follow-up requirements 8. Anticipated life expectancy of at least 3 months Specific Neuroimaging Inclusion Criteria: 1. Proven large vessel occlusion in ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) determined by MRA or CTA 2. Large infarct-core lesion on at least one of the following: * 2.1. Non-Contrast CT (ASPECTS of 3-5), * 2.2. CT perfusion (rCBF\<30% ≥50cc), * 2.3. MRI-DWI (ADC\<620 ≥50cc) Exclusion Criteria: 1. Inability to undergo CT angiography and/or CT perfusion imaging (e.g., renal insufficiency, iodine/contrast allergy) 2. Co-morbid psychiatric or medical illnesses that would confound the neurological assessments 3. Treatment with thrombolytic agent beyond 4.5 hours from last known well 4. Treated with thrombolytic agent 3-4.5 hours after last known well AND any of the following: * 1\) age \>80, * 2\) current anticoagulant use, * 3\) history of diabetes AND prior stroke, * 4\) NIHSS \>25, * 5\) ischemic involvement of \> 1/3 MCA territory 5. Current participation in another investigational drug or device study. Neuroimaging Exclusion Criteria 1. Patients who have both ASPECTS of 6-10 on non-contrast CT AND core volume \<50 cc on perfusion imaging 2. Patients with very large core on non-contrast CT i.e. ASPECTS ≤ 2 3. Evidence of intracranial tumor (except small meningioma), acute intracranial hemorrhage, neoplasm, or arteriovenous malformation 4. A significant mass effect with midline shift 5. Evidence of internal carotid artery dissection that is flow limiting or aortic dissection 6. Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device 7. Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion). 8. Signs of established infarct and large area of cerebral edema on non-contrast CT

Locations (31)

Outcomes

Primary Outcomes

Degree of Disability/Dependence as Measured by the Modified Rankin Scale (mRS) Score

The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead

Time frame: 90 days

Secondary Outcomes

Number of Participants That Achieved Functional Independence as Measured by a mRS Score of 0-2 at 90-day Follow-up

Time frame: 90 days

Number of Participants That Achieved Independent Ambulation as Measured by a mRS Score of 0-3 at 90-day Follow-up

Data from ClinicalTrials.gov

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