SELECT 2: A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke

SELECT 2 is a prospective, 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. The secondary aim is to look at the correlation of imaging profiles with thrombectomy
clinical outcomes and treatment effect.

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: 50-100cc, mismatch volume of ≥15cc
and mismatch ratio of ≥1.8) 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. The 2nd primary outcome is favorable clinical outcomes: mRS
score of 0-2. Secondary outcomes are 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 460 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 330 patients, at which time the study may stop for
efficacy or futility.

Inclusion Criteria:

1. Adults (18-85 years) with the final diagnosis of an acute ischemic stroke

2. CT-angiogram or MR-angiogram proven large artery occlusion in the distal ICA or MCA M1
locations

3. NIHSS ≥ 6

4. Last known well to groin puncture or medical management between 0 to 24 hours

5. Baseline modified Rankin Scale score of 0-1

6. Eligible for thrombectomy with stent retriever or medical management

7. Signed Informed Consent obtained

8. Subject willing to comply with the protocol follow-up requirements

9. Anticipated life expectancy of at least 3 months

10. IV-tPA eligible patients treated per FDA guidelines

Specific Neuroimaging Inclusion Criteria:

1. ICA or MCA M1 occlusion (carotid occlusions can be cervical or intracranial; with or
without tandem MCA lesions) determined by MRA or CTA

2. Non-contrast ASPECTS scores of 3-10 as determined by the treating physician, without
use of automated ASPECTS. The definitions of CT imaging profiles are:

1. ASPECT≥6 for favorable profiles

2. ASPECT 3-5 for unfavorable profiles*

3. CTP inclusion criteria are rCBF (<30%) 0-100cc, mismatch volume ≥15cc, and mismatch
ratio ≥1.8. MR perfusion will be allowed if CT perfusion is not available. The
definitions of CTP imaging profiles are:

1. rCBF (<30%) 0-50cc, mismatch volume of ≥15cc, and mismatch ratio of ≥1.8 for
favorable profiles

2. rCBF (<30%) 50-100cc, mismatch volume of ≥15cc, and mismatch ratio of ≥1.8 for
unfavorable profiles*

The definitions of MR Perfusion imaging profiles are:

1. ADC <620 0-50cc, mismatch volume of ≥15cc, and mismatch ratio of ≥1.8 for favorable
profiles

2. ADC <620 50-100cc, mismatch volume of ≥15cc, and mismatch ratio of ≥1.8 for
unfavorable profiles*

Exclusion Criteria:

1. Inability to undergo CT-Angiography and/or CT/MR Perfusion imaging (e.g., renal
insufficiency, iodine/contrast allergy)

2. Co-morbid psychiatric or medical illnesses that would confound the neurological
assessments

Neuroimaging Exclusion Criteria

1. Patients who have both favorable CT and favorable CTP/MRP

2. Patients with very large core on imaging

1. ASPECTS ≤ 2

2. rCBF (<30%) >100 or ADC <620 >100cc

3. Patients without established mismatch on CT perfusion

1. Mismatch ratio (Tmax>6s volume/[rCBF(<30%) volume or ADC < 620 volume) <1.8]) OR

2. Mismatch volume (Tmax>6s volume - rCBF(<30%) volume or ADC < 620 volume) <15 mL

4. Evidence of intracranial tumor (except small meningioma) acute intracranial
hemorrhage, neoplasm, or arteriovenous malformation

5. Significant mass effect with midline shift

6. Evidence of internal carotid artery dissection that is flow limiting or aortic
dissection

7. Intracranial stent implanted in the same vascular territory that precludes the safe
deployment/removal of the neurothrombectomy device

8. 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).