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

NCT03876457 | Completed Results DMC FDA Device

• 1 other identifier: G180275, Pro00056862
• Study Type: interventional
• Target: 352
• Locations: 6 countries
• Sites: 31

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.

Conditions

Acute Ischemic Stroke

Keywords

Ischemic stroke; Large vessel occlusion; Endovascular thrombectomy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Number of Participants That Achieved Functional Independence as Measured by a mRS Score of 0-2 at 90-day Follow-up

  90 days

• Number of Participants That Achieved Independent Ambulation as Measured by a mRS Score of 0-3 at 90-day Follow-up

  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

Other Outcomes (6)

• 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)

  24 hours to 7 days

• Number of Participants Who Suffered Parenchymal Hemorrhage Type 2

  24 hours

Study Arms (2)

Endovascular Thrombectomy plus Medical Management

EXPERIMENTAL

Device: Endovascular Thrombectomy; Other: Medical Management

Medical Management

ACTIVE COMPARATOR

Other: Medical Management

Interventions

Endovascular Thrombectomy DEVICE

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.

Endovascular Thrombectomy plus Medical Management

Medical Management OTHER

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.

Endovascular Thrombectomy plus Medical Management; Medical Management

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• Non-Contrast CT (ASPECTS of 3-5),
• CT perfusion (rCBF\<30% ≥50cc),
• MRI-DWI (ADC\<620 ≥50cc)

You may not qualify if:

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

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Stryker Neurovascular: collaborator
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (31)

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Baptist Health

Jacksonville, Florida, 32207, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Ascension St. Vincent Hospital

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Spectrum Health Hospital

Grand Rapids, Michigan, 49503, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Riverside Methodist Hospital - OhioHealth

Columbus, Ohio, 43214, United States

Location

Abington Jefferson Health

Abington, Pennsylvania, 19001, United States

Location

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Semmes Murphey Clinic - University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

Dell Seton Medical Center at the University of Texas at Austin

Austin, Texas, 78712, United States

Location

Valley Baptist Medical Center

Harlingen, Texas, 78550, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Ascension Wisconsin

Milwaukee, Wisconsin, 53215, United States

Location

Liverpool Hospital - South Western Sydney Clinical School

Liverpool, New South Wales, Australia

Location

The Royal Adelaide Hospital (RAH)

Adelaide, South Australia, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

Location

Christchurch Hospital

Christchurch, Canterbury, New Zealand

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Spain

Location

Universität Basel

Basel, Switzerland

Location

Related Publications (11)

• Sarraj A, Blackburn S, Abraham MG, Hussain MS, Ortega-Gutierrez S, Chen M, Kasner SE, Churilov L, Sitton CW, Pujara DK, Sundararajan S, Hu YC, Herial NA, Budzik RF, Hicks WJ, Vora N, Arenillas JF, Alfonso ML, Ramos Araque ME, Tsai JP, Abdulrazzak MA, Kozak O, Yan B, Mitchell PJ, Cordato DJ, Manning NW, Cheung A, Hanel RA, Aghaebrahim AN, Wu TY, Portela PC, Merchan AJP, Gandhi CD, Al-Mufti F, Samaniego EA, Maali L, Qureshi A, Lechtenberg CG, Slavin S, Rosterman L, Gibson D, Wallace AN, Sahlein D, Perez de la Ossa N, Hernandez Perez M, Schaafsma JD, Blasco J, Renu A, Sangha N, Warach S, Kleinig TJ, Mullen M, Elijovich L, Shaker F, Al-Shaibi FK, Johns H, Duncan KR, Opaskar A, Popovic MJ, Altose M, Ray A, Xiong W, Sunshine J, DeGeorgia M, Nguyen TN, Fifi JT, Tjoumakaris S, Jabbour P, Pereira VM, Lansberg MG, Albers GW, Sila C, Bambakidis N, Davis S, Wechsler L, Hill MD, Grotta JC, Ribo M, Hassan AE, Campbell BC; SELECT2 Investigators. General vs Nongeneral Anesthesia for Endovascular Thrombectomy in Patients With Large Core Strokes: A Prespecified Secondary Analysis of SELECT2 Trial. Neurology. 2025 Jul 22;105(2):e213819. doi: 10.1212/WNL.0000000000213819. Epub 2025 Jun 26.

  PMID: 40570276 DERIVED

• Yogendrakumar V, Campbell BCV, Johns HT, Churilov L, Ng FC, Sitton CW, Hassan AE, Abraham MG, Ortega-Gutierrez S, Hussain MS, Chen M, Kasner SE, Sharma G, Guha P, Pujara DK, Shaker F, Lansberg MG, Wechsler LR, Nguyen TN, Fifi JT, Hill MD, Ribo M, Parsons MW, Davis SM, Grotta JC, Albers GW, Sarraj A; SELECT2 Investigators. Association of Ischemic Core Hypodensity With Thrombectomy Treatment Effect in Large Core Stroke: A Secondary Analysis of the SELECT2 Randomized Controlled Trial. Stroke. 2025 Jun;56(6):1366-1375. doi: 10.1161/STROKEAHA.124.048899. Epub 2025 Mar 28.

  PMID: 40151939 DERIVED

• Ortega-Gutierrez S, Rodriguez-Calienes A, Pujara D, Sitton C, Galecio-Castillo M, Hassan AE, Abraham MG, Chen M, Blackburn S, Kasner SE, Olalde H, Ghannam M, Hussain MS, Leira EC, Martinez-Galdamez M, Shaban A, Tsai JP, Roeder H, Gudenkauf JC, Budzik R, Vora N, Hanel RA, Aghaebrahim A, Colgan F, de Miquel MA, Gandhi CD, Al-Mufti F, Blasco J, San Roman Manzanera L, Herial NA, Manning NW, Cheung A, Kozak O, Yan B, Mitchell PJ, Ebersole K, Toth G, Gooch M, Gibson D, Sahlein DH, Amuluru K, Abdulrazzak MA, Duncan K, Defta D, Shaker F, Al-Shaibi F, Ray A, Sunshine J, Hu YC, Burkhardt JK, Mir O, Alenzi B, Kass-Hout T, Gupta R, Tjoumakaris SI, Jabbour PM, Nguyen TN, Fifi JT, Pereira VM, Bambakidis N, Hill MD, Grotta JC, Ribo M, Campbell BCV, Samaniego EA, Sarraj A. Endovascular Thrombectomy for Extracranial Internal Carotid Artery Occlusions With Large Ischemic Strokes: Insights From the SELECT2 Trial. Neurology. 2025 Feb 25;104(4):e210269. doi: 10.1212/WNL.0000000000210269. Epub 2025 Jan 27.

  PMID: 39869840 DERIVED

• Tsai JP, Nguyen TN, Pujara DK, Fifi JT, Sundararajan S, Schaafsma JD, Perez de la Ossa N, Abraham MG, Chen M, Hussain MS, Ortega-Gutierrez S, Johns HT, Duncan KR, Churilov L, Lechtenberg CG, Slavin SJ, Opaskar A, de Lera M, Lara-Rodriguez B, Quesada H, Fournier LE, Defta DM, Shaker F, Sitton CW, Sharrief AZ, Grotta JC, Hill MD, Ribo M, Hassan AE, Campbell BCV, Sila C, Tjoumakaris SI, Sarraj A; for SELECT2 Investigators. Sex-Based Differences in Endovascular Thrombectomy Outcomes for Large Ischemic Stroke: A SELECT2 Subanalysis. Stroke. 2025 Feb;56(2):294-304. doi: 10.1161/STROKEAHA.124.049307. Epub 2025 Jan 2.

  PMID: 39744837 DERIVED

• Chen H, Malhotra A, Gandhi D. Thrombectomy for Large Strokes. N Engl J Med. 2024 Jul 25;391(4):378-379. doi: 10.1056/NEJMc2406965. No abstract available.

  PMID: 39047249 DERIVED

• Sarraj A, Hill MD, Hussain MS, Abraham MG, Ortega-Gutierrez S, Chen M, Kasner SE, Churilov L, Pujara DK, Johns H, Blackburn S, Sundararajan S, Hu YC, Herial NA, Budzik RF, Hicks WJ, Arenillas JF, Tsai JP, Kozak O, Cordato DJ, Hanel RA, Wu TY, Portela PC, Gandhi CD, Al-Mufti F, Maali L, Gibson D, Perez de la Ossa N, Schaafsma JD, Blasco J, Sangha N, Warach S, Kleinig TJ, Shaker F, Sitton CW, Nguyen T, Fifi JT, Jabbour P, Furlan A, Lansberg MG, Tsivgoulis G, Sila C, Bambakidis N, Davis S, Wechsler L, Albers GW, Grotta JC, Ribo M, Campbell BC, Hassan AE; SELECT2 Investigators; SELECT2 Collaborators; Vora N, Manning NW, Cheung A, Aghaebrahim AN, Paipa Merchan AJ, Sahlein D, Requena Ruiz M, Elijovich L, Arthur A, Al-Shaibi F, Samaniego EA, Duncan KR, Opaskar A, Ray A, Xiong W, Sunshine J, DeGeorgia M, Tjoumakaris S, Mendes Pereira V; SELECT2 Collaborators. Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial. JAMA Neurol. 2024 Feb 8;81(4):327-35. doi: 10.1001/jamaneurol.2024.0206. Online ahead of print.

  PMID: 38363872 DERIVED

• Sarraj A, Abraham MG, Hassan AE, Blackburn S, Kasner SE, Ortega-Gutierrez S, Hussain MS, Chen M, Johns H, Churilov L, Pujara DK, Shaker F, Maali L, Cardona Portela P, Herial NA, Gibson D, Kozak O, Arenillas JF, Yan B, Perez de la Ossa N, Sundararajan S, Hu YC, Cordato DJ, Manning NW, Hanel RA, Aghaebrahim AN, Budzik RF, Hicks WJ, Blasco J, Wu TY, Tsai JP, Schaafsma JD, Gandhi CD, Al-Mufti F, Sangha N, Warach S, Kleinig TJ, Yogendrakumar V, Ng F, Samaniego EA, Abdulrazzak MA, Parsons MW, Rahbar MH, Nguyen TN, Fifi JT, Mendes Pereira V, Lansberg MG, Albers GW, Furlan AJ, Jabbour P, Sitton CW, Sila C, Bambakidis N, Davis SM, Wechsler L, Hill MD, Grotta JC, Ribo M, Campbell BCV; SELECT2 Investigators. Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial. Lancet. 2024 Feb 24;403(10428):731-740. doi: 10.1016/S0140-6736(24)00050-3. Epub 2024 Feb 9.

  PMID: 38346442 DERIVED

• Sarraj A, Hassan AE, Abraham MG, Ortega-Gutierrez S, Kasner SE, Hussain MS, Chen M, Churilov L, Johns H, Sitton CW, Yogendrakumar V, Ng FC, Pujara DK, Blackburn S, Sundararajan S, Hu YC, Herial NA, Arenillas JF, Tsai JP, Budzik RF, Hicks WJ, Kozak O, Yan B, Cordato DJ, Manning NW, Parsons MW, Cheung A, Hanel RA, Aghaebrahim AN, Wu TY, Portela PC, Gandhi CD, Al-Mufti F, Perez de la Ossa N, Schaafsma JD, Blasco J, Sangha N, Warach S, Kleinig TJ, Shaker F, Al Shaibi F, Toth G, Abdulrazzak MA, Sharma G, Ray A, Sunshine J, Opaskar A, Duncan KR, Xiong W, Samaniego EA, Maali L, Lechtenberg CG, Renu A, Vora N, Nguyen T, Fifi JT, Tjoumakaris SI, Jabbour P, Tsivgoulis G, Pereira VM, Lansberg MG, DeGeorgia M, Sila CA, Bambakidis N, Hill MD, Davis SM, Wechsler L, Grotta JC, Ribo M, Albers GW, Campbell BC; SELECT2 Investigators. Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles. JAMA. 2024 Mar 5;331(9):750-763. doi: 10.1001/jama.2024.0572.

  PMID: 38324414 DERIVED

• Sarraj A, Hassan AE, Abraham MG, Ortega-Gutierrez S, Kasner SE, Hussain MS, Chen M, Blackburn S, Sitton CW, Churilov L, Sundararajan S, Hu YC, Herial NA, Jabbour P, Gibson D, Wallace AN, Arenillas JF, Tsai JP, Budzik RF, Hicks WJ, Kozak O, Yan B, Cordato DJ, Manning NW, Parsons MW, Hanel RA, Aghaebrahim AN, Wu TY, Cardona-Portela P, Perez de la Ossa N, Schaafsma JD, Blasco J, Sangha N, Warach S, Gandhi CD, Kleinig TJ, Sahlein D, Elijovich L, Tekle W, Samaniego EA, Maali L, Abdulrazzak MA, Psychogios MN, Shuaib A, Pujara DK, Shaker F, Johns H, Sharma G, Yogendrakumar V, Ng FC, Rahbar MH, Cai C, Lavori P, Hamilton S, Nguyen T, Fifi JT, Davis S, Wechsler L, Pereira VM, Lansberg MG, Hill MD, Grotta JC, Ribo M, Campbell BC, Albers GW; SELECT2 Investigators. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. N Engl J Med. 2023 Apr 6;388(14):1259-1271. doi: 10.1056/NEJMoa2214403. Epub 2023 Feb 10.

  PMID: 36762865 DERIVED

• 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.

  PMID: 35450966 DERIVED

• 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.

  PMID: 34282987 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Practice Management, Medical

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Practice Management; Professional Practice; Organization and Administration; Health Services Administration

Results Point of Contact

• Title: Dr. Amrou Sarraj
• Organization: University Hospitals Cleveland Medical Center

Amrou.Sarraj@UHhospitals.org

(216)844-0474

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 15, 2019
• Study Start: October 11, 2019
• Primary Completion: November 20, 2022
• Study Completion: November 16, 2023
• Last Updated: November 21, 2024
• Results First Posted: March 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); NZ (1); US (19); ES (5); CH (1); AU (3)