Clinical trial NCT03876457: SELECT2: A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke
Official title: SELECT2: A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Ischemic stroke
Large vessel occlusion
Endovascular thrombectomy
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: Stryker Neurovascular
name: The University of Texas Health Science Center, Houston
First posted: 2019-03-15
Enrollment: 352
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Degree of Disability/Dependence as Measured by the Modified Rankin Scale (mRS) Score
timeFrame: 90 days
Secondary outcomes:
measure: Number of Participants That Achieved Functional Independence as Measured by a mRS Score of 0-2 at 90-day Follow-up
timeFrame: 90 days
measure: Number of Participants That Achieved Independent Ambulation as Measured by a mRS Score of 0-3 at 90-day Follow-up
timeFrame: 90 days
measure: Number of Patients That Suffered a Symptomatic Intracranial Hemorrhage (sICH) as Measured by the SITS-MOST Criteria
timeFrame: 24 hours
measure: Number of Participants With Neurological Worsening Defined as a ≥4-point Increase on the NIHSS Score Due to the Stroke Itself
timeFrame: 24 hours
measure: Number of Mortalities Within 90-day Follow-up
timeFrame: 90 days
measure: Number of Procedural Complications
timeFrame: 24 hours
measure: Successful Reperfusion in the EVT Group, Defined as Modified Thrombolysis in Cerebral Ischemia (mTICI) Grade of 2b or Higher
timeFrame: at the end of endovascular thrombectomy procedure
measure: Discharge Location
timeFrame: day 5-7 after randomization/at discharge (whichever is later)
measure: 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
timeFrame: 24 hours
measure: Quality of Life Score, as Measured Using NeuroQOL at 90-day Follow-up
timeFrame: 90 days
measure: The 1-year Functional Outcome, as Measured by the Modified Rankin Scale Score
timeFrame: 1 year
measure: Number of Participants With Functional Independence, Defined as mRS Score of 0-2 at 1-year Follow-up
timeFrame: 1 year
measure: Number of Participants With Independent Ambulation, Defined as mRS Score of 0-3 at 1-year Follow-up
timeFrame: 1 year
measure: Quality of Life Score, as Measured Using NeuroQOL at 1 Year Follow-up
timeFrame: 1 year
Other outcomes:
measure: Infarct Volume on MRI DWI Sequence (or CT if MRI Not Feasible) up to 7 Days After Randomization
timeFrame: Up to 7 days
measure: Lesion Growth (Difference Between the Ischemic Core on Baseline Imaging and the Follow-up Infarct Volume)
timeFrame: 24 hours to 7 days
measure: Number of Participants Who Suffered Parenchymal Hemorrhage Type 2
timeFrame: 24 hours
measure: Number of Participants Who Suffered a Subarachnoid Hemorrhage
timeFrame: 24 hours
measure: Number of Participants Who Had a Hemicraniectomy During Index Hospitalization
timeFrame: day 5-7 after randomization/at discharge (whichever is later)
measure: Length of Hospital Stay
timeFrame: Up to 90-day follow up visit
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Jacksonville
country: United States
facility: Baptist Health
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital
state: Michigan
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital - OhioHealth
state: Ohio
city: Abington
country: United States
facility: Abington Jefferson Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: Semmes Murphey Clinic - University of Tennessee Health Science Center
state: Tennessee
city: Austin
country: United States
facility: Dell Seton Medical Center at the University of Texas at Austin
state: Texas
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Milwaukee
country: United States
facility: Ascension Wisconsin
state: Wisconsin
city: Liverpool
country: Australia
facility: Liverpool Hospital - South Western Sydney Clinical School
state: New South Wales
city: Adelaide
country: Australia
facility: The Royal Adelaide Hospital (RAH)
state: South Australia
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
state: Ontario
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: Canterbury
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Basel
country: Switzerland
facility: Universität Basel
Study officials:
affiliation: Case Western Reserve University - University Hospitals Cleveland Medical Center
name: Amrou Sarraj, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health
name: (Australia and Oceania) Bruce CV Campbell, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vall d'Hebron University Hospital, Barcelona
name: (Europe) Marc Ribo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.