Acute Ischemic Stroke
Conditions
Keywords
Endovascular Thrombectomy, Mechanical Thrombectomy
Brief summary
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
DEVICEEndovascular 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 combination approach at the discretion of the treating physician, using devices approved by the local regulatory authority. For patients treated in the United States of America, only US Food and Drug Administration-approved neurothrombectomy devices can be used.
OTHERMedical 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 etiology identification by requisite neurology , cardiology, immunology evaluations and 4) short and long-term strategies for secondary stroke prevention, including anticoagulation, antiplatelet therapy, medical optimization and modification of stroke risk factors such as hypertension, hyperlipidemia, diabetes and other potential comorbidities.
Sponsors
Amrou Sarraj
Patient-Centered Outcomes Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The distribution of the modified Rankin Scale score | 90 days ± 15 days | The modified Rankin Scale (a 7-point scoring system, 0 indicates no residual stroke symptoms and 6 represents death) is assessed through patient/caregiver interview by trained and certified raters. The modified Rankin Scale score is the standard FDA-recognized measure of stroke outcome, used in clinical trials testing acute stroke therapies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Utility-weighted modified Rankin Scale scores | 90 days ± 15 days | The Utility-Weighted Modified Rankin Scale (UW-mRS) is an advancement in the assessment of disability and functional independence for patients with neurological conditions. By incorporating patient preferences, it complements the traditional Modified Rankin Scale (mRS) by capturing individual preferences for specific health states. UW mRS is calculated by incorporating responses from the EuroQol-5 Dimension (EQ-5D) questionnaire, with a maximum score of 10 and minimum score of 0 and higher score indicating better functional status. |
| Domain-specific scores for NeuroQoL | 90 days ± 15 days | The Neuro-Quality of Life (Neuro-QoL) measurement system evaluates health-related quality of life (HRQoL) in patients with neurological conditions through patient-reported outcomes, incorporating the impact of diseases and treatments on patients' daily lives and well-being. Neuro-QoL comprises item banks in Motor, Social, Cognitive and Depression modules. Responses to questions are converted into T-scores ranging from 0 to 100, with higher scores for Motor, Social and Cognitive domains indicating better quality of life and higher scores for depression domain indicating worse quality of life. |
| Functional independence (mRS 0-2) | 90 days ± 15 days | Functional independence is identified by pooling all patients achieving a) no stroke deficits (mRS of 0), b) minimal stroke deficits without any functional limitations (mRS of 1) and c) functional limitations that do not interfere with independent living (mRS of 2) and illustrates being able to execute all day to day activities required for independent living, including bathing and dressing, cooking, grocery shopping and handling finances, with or without some degree of stroke deficits present. |
| The distribution of the modified Rankin Scale score | 1 year ± 30 days | The modified Rankin Scale (a 7-point scoring system, 0 indicates no residual stroke symptoms and 6 represents death) is assessed through patient/caregiver interview by trained and certified raters. The modified Rankin Scale score is the standard FDA-recognized measure of stroke outcome, used in clinical trials testing acute stroke therapies. |
Countries
United States
Contacts
CONTACTKate Rownd, MED
CONTACTDeep Pujara, MBBS, MPH, MS
PRINCIPAL_INVESTIGATORAmrou Sarraj, MD
University Hospitals
Outcome results
None listed