Overview
SELECT LATE trial aims to evaluate if addition of endovascular thrombectomy to medical management in patients presenting with acute ischemic stroke and a proximal large vessel occlusion in the anterior circulation between 24 and 72 hours of stroke onset results in achieving better functional outcomes (measured using modified Rankin Scale Scores) at 90-day follow-up (± 15 days).
Description
SELECT LATE is a prospective, phase III, randomized, international, multicenter, assessor-blinded controlled trial evaluating if addition of endovascular thrombectomy to medical management in patients presenting with acute ischemic stroke and a proximal large vessel occlusion in the anterior circulation between 24 and 72 hours of stroke onset results in achieving better functional outcomes (measured using modified Rankin Scale Scores) at 90-day follow-up (± 15 days).
Patients with the final diagnosis of an acute ischemic stroke due to a large vessel occlusion in the internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA), who present between 24-72 hours of when they were last known to be well and meet neuroimaging eligibility criteria \[Non-contrast CT ASPECTS 3-10 and Ischemic core volume ≤150ml\] will be randomized in a 1:1 ratio to thrombectomy plus medical management vs medical management alone. Patient assessments will be made at baseline, 24 hours post-randomization, discharge, 90 days and 1 year.
The primary endpoint is the Modified Rankin Scale (mRS) score at 90 (+/- 15) days. The primary outcome is a shift on 90-day mRS scores, with scores of 5 (severe disability requiring constant care) and 6 (death) merged to avoid considering a shift from 6 to 5 as an improvement. Secondary outcomes include functional independence (mRS score of 0-2), Utility weighted mRS, and Quality of Life measures. Safety outcomes include mortality, severe disability or death (mRS 5-6), incidence of symptomatic intracranial hemorrhage (sICH per SITS-MOST); and Imaging outcomes include infarct volume on MRI diffusion-weighted imaging (DWI) sequence (or CT if MRI is not feasible) 24-72 hours after randomization.
A maximum of 408 patients will be randomized across the study sites. Online randomization with Common Scale-Minimum Sufficient Balance algorithm will be used to balance the distribution of important variables. Interim analyses will be conducted at 136 and 272 patients, at which time the study may stop for efficacy or futility.
Eligibility
Inclusion Criteria:
General Inclusion Criteria:
- Adults (18-85\ years) with the final diagnosis of an acute ischemic stroke$
- NIHSS ≥ 6
- Time from last-known-well to randomization \>24 - 72 hours
- Pre-stroke modified Rankin Scale score of 0-1
- Eligible for thrombectomy and medical management
- Signed Informed Consent obtained
- Subject willing to comply with the protocol follow-up requirements
- Anticipated life expectancy of at least 3 months \Inclusive of both 18 and 85 years of age (i.e. up to 86th birthdate). $Subacute presentation - In-hospital stroke admissions with fluctuating clinical symptoms for patients who presented to EVT centers within 24 hours of when they were last known well will not be eligible for the trial.
General Exclusion Criteria
- Current participation in another investigational interventional drug or device study.
- Baseline Platelet count \<100,000/μl
Imaging Inclusion Criteria
- Proven large vessel occlusion in ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions), as determined by MR Angiography (MRA) or CT Angiography (CTA)
- CT ASPECTS 3-10
- CT Perfusion ischemic core (rCBF \<30%) volume ≤150 ml OR MR Diffusion ischemic core (ADC \<620x10-6 mm2/s) volume ≤150ml #If the perfusion software at enrollment center uses another threshold/measure to define ischemic core, please use that measure to assess ischemic core criteria.
Imaging Exclusion Criteria
- Evidence of intracranial tumor (except small meningioma \<3cm without signs of edema or inflammation), acute intracranial hemorrhage, or arteriovenous malformation
- Significant mass effect, defined as midline shift (\>3mm) using foramen of monroe (anterior margin of third ventricle) as the marker for midline instead of septum pellucidum AND/OR Effacement of sulci in contralateral hemisphere
- Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
- Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device
- 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).
- Any signs of established infarct, demarcating hypodensity and area of cerebral edema on non-contrast CT
- CT ASPECTS 0-2
- CT Perfusion ischemic core (rCBF \<30%) volume \>150 ml OR MR Diffusion ischemic core (ADC \<620x10-6 mm2/s) volume \>150ml #If the perfusion software at enrollment center uses another threshold/measure to define ischemic core, please use that measure to assess ischemic core criteria.
