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

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Device: Endovascular Thrombectomy; Other: Medical Management

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.

• Study Type: Interventional
• Enrollment (Actual): 352
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia
      • Liverpool Hospital - South Western Sydney Clinical School
  • South Australia
    • Adelaide, South Australia, Australia
      • The Royal Adelaide Hospital (RAH)
  • Victoria
    • Melbourne, Victoria, Australia
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • Ontario
    • Toronto, Ontario, Canada
      • University Health Network - Toronto Western Hospital
• New Zealand
  • Canterbury
    • Christchurch, Canterbury, New Zealand
      • Christchurch Hospital
• Spain
  • Badalona, Spain
    • Hospital Universitario Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona
  • Valladolid, Spain
    • Hospital Clinico Universitario de Valladolid
• Switzerland
  • Basel, Switzerland
    • Universität Basel
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Health
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Ascension St. Vincent Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospital
  • New York
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital - OhioHealth
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Jefferson Health
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • The Hospital of the University of Pennsylvania
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Semmes Murphey Clinic - University of Tennessee Health Science Center
  • Texas
    • Austin, Texas, United States, 78712
      • Dell Seton Medical Center at the University of Texas at Austin
    • Harlingen, Texas, United States, 78550
      • Valley Baptist Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Ascension Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Specific Neuroimaging Inclusion Criteria:

1. 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

2. 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:

1. Inability to undergo CT angiography and/or CT perfusion imaging (e.g., renal insufficiency, iodine/contrast allergy)
2. Co-morbid psychiatric or medical illnesses that would confound the neurological assessments
3. Treatment with thrombolytic agent beyond 4.5 hours from last known well

4. Treated with thrombolytic agent 3-4.5 hours after last known well AND any of the following:

   • 1) age >80,
   • 2) current anticoagulant use,
   • 3) history of diabetes AND prior stroke,
   • 4) NIHSS >25,
   • 5) ischemic involvement of > 1/3 MCA territory
5. Current participation in another investigational drug or device study.

Neuroimaging Exclusion Criteria

1. Patients who have both ASPECTS of 6-10 on non-contrast CT AND core volume <50 cc on perfusion imaging
2. Patients with very large core on non-contrast CT i.e. ASPECTS ≤ 2
3. Evidence of intracranial tumor (except small meningioma), acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
4. A significant mass effect with midline shift
5. Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
6. Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device
7. 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).
8. Signs of established infarct and large area of cerebral edema on non-contrast CT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endovascular Thrombectomy plus Medical Management	Device: Endovascular Thrombectomy; Patients randomized to endovascular thrombectomy arm will receive thrombectomy plus medical management. They will be treated with thrombectomy devices (stent-retrievers or aspiration devices) currently cleared by the FDA for thrombus removal in patients experiencing an acute stroke within 24 hours of symptom onset. The devices which will be used are FDA-approved stent retrievers: the Trevo Retriever, the Solitaire Revascularization Device, EmboTrap Revascularization Device and Tigertriever Revascularization Device; and/or the aspiration devices approved by the FDA (e.g. MicroVention SOFIA Catheter, and the Penumbra thrombectomy system). The choice of thrombectomy method, primary approach/technique, whether primary aspiration or primary stent-retriever with or without aspiration, will be left up to the interventionalist, with any of the FDA-approved devices approved in the study protocol or a combination of them.; Other: Medical Management; Patients will receive standard AHA guideline-directed medical therapy, which will include IV thrombolytic therapy available for use according to practice guidelines in patients presenting within the first 3 hours from last-seen-normal and meeting other FDA label criteria, or up to 4.5 hours from last-seen-normal and meeting other AHA guidelines. For non-thrombolysis treated patients, this will include aspirin 325 mg on day 1 followed by aspirin 81 mg or 325 mg thereafter, which will be determined by treating physician and standard deep venous thrombosis prevention therapy. Intravenous anticoagulation and dual anti-platelet therapy will be discouraged without clear documented reasoning. Post-thrombolysis patients will be treated based on standard study site protocols for these patients.
Active Comparator: Medical Management	Other: Medical Management; Patients will receive standard AHA guideline-directed medical therapy, which will include IV thrombolytic therapy available for use according to practice guidelines in patients presenting within the first 3 hours from last-seen-normal and meeting other FDA label criteria, or up to 4.5 hours from last-seen-normal and meeting other AHA guidelines. For non-thrombolysis treated patients, this will include aspirin 325 mg on day 1 followed by aspirin 81 mg or 325 mg thereafter, which will be determined by treating physician and standard deep venous thrombosis prevention therapy. Intravenous anticoagulation and dual anti-platelet therapy will be discouraged without clear documented reasoning. Post-thrombolysis patients will be treated based on standard study site protocols for these patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of Disability/Dependence as Measured by the Modified Rankin Scale (mRS) Score	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	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Achieved Functional Independence as Measured by a mRS Score of 0-2 at 90-day Follow-up	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	90 days
Number of Participants That Achieved Independent Ambulation as Measured by a mRS Score of 0-3 at 90-day Follow-up	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	90 days
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	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	24 hours
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	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.	90 days
The 1-year Functional Outcome, as Measured by the Modified Rankin Scale Score	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	1 year
Number of Participants With Functional Independence, Defined as mRS Score of 0-2 at 1-year Follow-up	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	1 year
Number of Participants With Independent Ambulation, Defined as mRS Score of 0-3 at 1-year Follow-up	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	1 year
Quality of Life Score, as Measured Using NeuroQOL at 1 Year Follow-up	Quality of Life scores in mobility, depression,social and cognitive domains	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Suffered Parenchymal Hemorrhage Type 2		24 hours
Number of Participants Who Suffered a Subarachnoid Hemorrhage		24 hours
Number of Participants Who Had a Hemicraniectomy During Index Hospitalization		day 5-7 after randomization/at discharge (whichever is later)
Length of Hospital Stay	Was assessed if the patient was discharged at every follow-up visit to determine the length of the stay if the patient was not discharged at the time of previous follow-up visit.	Up to 90-day follow up visit
Infarct Volume on MRI DWI Sequence (or CT if MRI Not Feasible) up to 7 Days After Randomization	Infarct volume on MRI DWI sequence (or CT if MRI not feasible) up to 7 days after randomization	Up to 7 days
Lesion Growth (Difference Between the Ischemic Core on Baseline Imaging and the Follow-up Infarct Volume)	Lesion growth (difference between ischemic core on baseline imaging and the follow-up infarct volume)	24 hours to 7 days

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: The University of Texas Health Science Center, Houston; Stryker Neurovascular
• Investigators: Principal Investigator: Amrou Sarraj, MD, Case Western Reserve University - University Hospitals Cleveland Medical Center; Principal Investigator: (Australia and Oceania) Bruce CV Campbell, MBBS PhD, Melbourne Health; Principal Investigator: (Europe) Marc Ribo, MD, Vall d'Hebron University Hospital, Barcelona

Publications and helpful links

General Publications

• Sarraj A, Campbell BCV, Christensen S, Sitton CW, Khanpara S, Riascos RF, Pujara D, Shaker F, Sharma G, Lansberg MG, Albers GW; SELECT Investigators. Accuracy of CT Perfusion-Based Core Estimation of Follow-up Infarction: Effects of Time Since Last Known Well. Neurology. 2022 May 24;98(21):e2084-e2096. doi: 10.1212/WNL.0000000000200269. Epub 2022 Apr 21.
• Sarraj A, Hassan AE, Abraham M, Ribo M, Blackburn S, Chen M, Hussain MS, Pereira VM, Ortega-Gutierrez S, Sitton C, Lavori PW, Cai C, Rahbar M, Pujara D, Shaker F, Lansberg MG, Campbell B, Grotta JC, Albers GW; SELECT2 Investigators. A randomized controlled trial to optimize patient's selection for endovascular treatment in acute ischemic stroke (SELECT2): Study protocol. Int J Stroke. 2022 Jul;17(6):689-693. doi: 10.1177/17474930211035032. Epub 2021 Dec 15.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2019
• Primary Completion (Actual): November 20, 2022
• Study Completion (Actual): November 16, 2023

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Ischemic stroke; Large vessel occlusion; Endovascular thrombectomy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia
• Other Study ID Numbers: G180275, Pro00056862

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes