Medical Management With Endovascular Thrombectomy Versus Medical Management Alone in Patients Presenting Beyond 24 Hours of Last Known Well

Official title

Medical Management With Endovascular Thrombectomy Versus Medical Management Alone in Patients Presenting Beyond 24 Hours of Last Known Well - SELECT LATE Trial

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).

Detailed 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.

Interventions

• Device Endovascular Thrombectomy
  EVT will be provided in addition to medical management and is a procedure to remove a thrombus in one of the brain arteries that is obstructing the blood flow and is responsible for the occurrence of stroke. Removing this occlusion results in restoration of blood flow to ischemic brain tissue and salvages the parts that are still viable, which is expected to improve functional outcomes. Endovascular thrombectomy procedure will be performed using stent retrievers, aspiration devices or combinatio
• Other Medical Management
  Medical management comprises various measures to prevent further deterioration, enhance patients' outcomes and prevent occurrence of a secondary stroke in short and long term. This includes 1) evidence-based practices for blood pressure management 2) Neurocritical care monitoring with appropriate osmotic therapy and neurosurgical interventions such as hemicraniectomy for management of cerebral edema that occurs due to infracted brain tissue based on local institutional protocol, 3) stroke etiolo

Primary outcome measures

• The distribution of the modified Rankin Scale score [Time frame: 90 days ± 15 days]

Secondary outcome measures (7)

• Utility-weighted modified Rankin Scale scores [Time frame: 90 days ± 15 days]
• Domain-specific scores for NeuroQoL [Time frame: 90 days ± 15 days]
• Functional independence (mRS 0-2) [Time frame: 90 days ± 15 days]
• The distribution of the modified Rankin Scale score [Time frame: 1 year ± 30 days]
• Functional independence (mRS 0-2) [Time frame: 1 year ± 30 days]
• Utility-weighted modified Rankin Scale scores [Time frame: 1 year ± 30 days]
• Domain-specific scores for NeuroQoL [Time frame: 1 year ± 30 days]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 6 centers

• University of Chicago — Chicago
• The University of Kansas Health System — Kansas City
• Washington University School of Medicine — St Louis
• Rhode Island Hospital — Providence
• Baylor University Medical Center — Dallas
• West Virginia University — Morgantown

Identifiers

NCT: NCT07115940 · STUDY20250993 · G250153

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗