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

Not Applicable

Completed

Conditions: Acute Ischemic Stroke

Interventions: Device: Endovascular Thrombectomy
Other: Medical Management

Registration Number: NCT03876457

Lead Sponsor: University Hospitals Cleveland Medical Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 352

Inclusion Criteria

Adults (18-85 years) with the final diagnosis of an acute ischemic stroke
NIH Stroke Scale Score (NIHSS) ≥ 6
Last known well to groin puncture or medical management between 0 to 24 hours
Pre-stroke modified Rankin Scale score (mRS) of 0-1
Eligible for thrombectomy or medical management
Signed Informed Consent obtained
Subject willing to comply with the protocol follow-up requirements
Anticipated life expectancy of at least 3 months

Specific Neuroimaging 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) determined by MRA or CTA
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

Inability to undergo CT angiography and/or CT perfusion imaging (e.g., renal insufficiency, iodine/contrast allergy)
Co-morbid psychiatric or medical illnesses that would confound the neurological assessments
Treatment with thrombolytic agent beyond 4.5 hours from last known well
Treated with thrombolytic agent 3-4.5 hours after last known well AND any of the following:
- 1. age >80,
- 1. current anticoagulant use,
- 1. history of diabetes AND prior stroke,
- 1. NIHSS >25,
- 1. ischemic involvement of > 1/3 MCA territory
Current participation in another investigational drug or device study.

Neuroimaging Exclusion Criteria

Patients who have both ASPECTS of 6-10 on non-contrast CT AND core volume <50 cc on perfusion imaging
Patients with very large core on non-contrast CT i.e. ASPECTS ≤ 2
Evidence of intracranial tumor (except small meningioma), acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
A significant mass effect with midline shift
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).
Signs of established infarct and large area of cerebral edema on non-contrast CT

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Endovascular Thrombectomy plus Medical Management	Endovascular Thrombectomy	-
Endovascular Thrombectomy plus Medical Management	Medical Management	-
Medical Management	Medical Management	-

Primary Outcome Measures

Name	Time	Method
Degree of Disability/Dependence as Measured by the Modified Rankin Scale (mRS) Score	90 days	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants That Achieved Functional Independence as Measured by a mRS Score of 0-2 at 90-day Follow-up	90 days	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
Number of Participants That Achieved Independent Ambulation as Measured by a mRS Score of 0-3 at 90-day Follow-up	90 days	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
Number of Patients That Suffered a Symptomatic Intracranial Hemorrhage (sICH) as Measured by the SITS-MOST Criteria	24 hours
Number of Participants With Neurological Worsening Defined as a ≥4-point Increase on the NIHSS Score Due to the Stroke Itself	24 hours
Number of Mortalities Within 90-day Follow-up	90 days
Number of Procedural Complications	24 hours	The following were included in the complications counted: * Surgical site hematoma * Surgical site infection * Vascular injury (peripheral or intracranial dissection, perforation or others) caused by the endovascular procedure
Successful Reperfusion in the EVT Group, Defined as Modified Thrombolysis in Cerebral Ischemia (mTICI) Grade of 2b or Higher	at the end of endovascular thrombectomy procedure
Discharge Location	day 5-7 after randomization/at discharge (whichever is later)
Number of Participants That Showed Early Neurological Improvement, Defined as Improvement of ≥8 Points on NIHSS at 24 Hours of Presentation or an NIHSS of 0-1	24 hours
Quality of Life Score, as Measured Using NeuroQOL at 90-day Follow-up	90 days	The Neurological Quality of Life score (NeuroQoL) is a patient-reported outcome measure that assesses the impact of neurological disorders on various aspects of a person's quality of life in neurological diseases and has measures developed across 17 different domains. The trial measured NeuroQoL scores for Mobility, Depression, Social and Cognitive domains. The scores provide a measure of an individual's quality of life in a given domain relative to a reference population, with a mean score of 50 and range of 0-100. A t-score of 50 indicates average quality of life, while scores above 50 indicate better-than-average quality of life and scores below 50 indicate poorer-than-average quality of life, except for depression domain - where lower scores indicate better and higher scores indicate worse quality of life.
The 1-year Functional Outcome, as Measured by the Modified Rankin Scale Score	1 year	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
Number of Participants With Functional Independence, Defined as mRS Score of 0-2 at 1-year Follow-up	1 year	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
Number of Participants With Independent Ambulation, Defined as mRS Score of 0-3 at 1-year Follow-up	1 year	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
Quality of Life Score, as Measured Using NeuroQOL at 1 Year Follow-up	1 year	Quality of Life scores in mobility, depression,social and cognitive domains

Trial Locations

Locations (31): Kaiser Permanente
🇺🇸
Los Angeles, California, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Westchester Medical Center
🇺🇸
Valhalla, New York, United States
University Hospitals Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
Riverside Methodist Hospital - OhioHealth
🇺🇸
Columbus, Ohio, United States
The Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
The University of Texas Health Science Center at Houston
🇺🇸
Houston, Texas, United States
Liverpool Hospital - South Western Sydney Clinical School
🇦🇺
Liverpool, New South Wales, Australia
The Royal Adelaide Hospital (RAH)
🇦🇺
Adelaide, South Australia, Australia
University Health Network - Toronto Western Hospital
🇨🇦
Toronto, Ontario, Canada
Spectrum Health Hospital
🇺🇸
Grand Rapids, Michigan, United States
Royal Melbourne Hospital
🇦🇺
Melbourne, Victoria, Australia
Universität Basel
🇨🇭
Basel, Switzerland
Ascension St. Vincent Hospital
🇺🇸
Indianapolis, Indiana, United States
Ascension Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Baptist Health
🇺🇸
Jacksonville, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Abington Jefferson Health
🇺🇸
Abington, Pennsylvania, United States
Semmes Murphey Clinic - University of Tennessee Health Science Center
🇺🇸
Memphis, Tennessee, United States
Valley Baptist Medical Center
🇺🇸
Harlingen, Texas, United States
University of Alberta
🇨🇦
Edmonton, Alberta, Canada
Hospital Universitario Germans Trias i Pujol
🇪🇸
Badalona, Spain
Christchurch Hospital
🇳🇿
Christchurch, Canterbury, New Zealand
Hospital Clínic i Provincial de Barcelona
🇪🇸
Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸
Barcelona, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸
Valladolid, Spain
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Dell Seton Medical Center at the University of Texas at Austin
🇺🇸
Austin, Texas, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States