Endovascular Therapy for Low NIHSS Ischemic Strokes

Phase 2

Recruiting

Conditions: Cerebral Ischemia

Interventions: Device: Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device
Combination Product: Initial medical management (iMM)

Registration Number: NCT04167527

Lead Sponsor: Emory University

Brief Summary: This study will test the hypothesis that patients presenting within 8 hours of onset with cerebral ischemia in the setting of proximal large vessel occlusions (LVO) and low baseline NIHSS scores (0-5) will have better 90-day clinical outcomes (mRS distribution) with immediate mechanical thrombectomy (iMT) compared to initial medical management (iMM).

Detailed Description: Currently, the vast majority of these patients do not receive immediate vessel imaging with either CT- or MR-angiography. However, acute ischemic stroke patients with low NIHSS who harbor a large vessel occlusion (LVO) later decline in 20-40% of cases, and/or have underappreciated impairments related to their relatively mild strokes. Similarly, LVO patients presenting with a transient ischemic attack (TIA) are under increased risk of clinical deterioration. Such patients with apparent good collateral circulation, and hence a substantial perfusion of the vascular territory of the occluded large artery, likely have the most to gain from endovascular revascularization. At the same time, this collateral perfusion may allow for more frequent recanalization, either spontaneously or by intravenous (IV) rtPA. Experience with immediate mechanical thrombectomy (iMT) in the LVO mild stroke target population is limited.

This study will test the hypothesis that patients presenting within 8 hours of onset with cerebral ischemia in the setting of proximal large vessel occlusions (LVO) and low baseline NIHSS scores (0-5) will have better 90-day clinical outcomes (mRS distribution) with immediate mechanical thrombectomy (iMT) compared to initial medical management (iMM).

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 200

Inclusion Criteria

Age 18 years or older
Acute ischemic stroke based on clinical diagnosis (NIHSS 0-5) and presence of an objective neurological deficit
Patients eligible for intravenous rt-PA should receive this therapy as soon as possible and no later than 4.5 hours from symptom onset
Proximal Intracranial Artery Occlusion on Imaging by NCCT/CTA or MRI/MRA showing complete occlusion of the intracranial ICA, M1, or an "M1-like" M2 vessel with or without tandem cervical lesion. Notably, "M1-like" M2 vessel occlusions are defined functionally for the trial as following:
1. On CTA: Occlusion of both branches after MCA division (both M2s occluded) or occlusion of the larger diameter M2 branch . In case of trifurcations, either the two largest M2 branches are occluded or the occluded M2 has a larger diameter than the combined diameter of the two other M2s . Notably, the M2 origins are defined by the first branching point in the MCA other than the anterior temporal artery rather than by anatomic landmarks (e.g., horizontal versus insular location).
  
  or
2. If mCTA or CTP performed (optional): a M2 occlusion which supplies a large proportion of the MCA territory by evidence of either:
i. The bulk (>2/3) of the MCA territory has evidence of delayed washout on multiphase CT or ii. Perfusion imaging shows a hypoperfusion lesion volume involving a significant proportion of the MCA territory defined as Tmax >4 sec lesion of ≥100 mL
Baseline Infarct Core of either:
1. Baseline ASPECTS ≥6 on non-contrast CT (NCCT), or
2. Baseline Infarct Core Volume of < 70cc on either CTP (Volume of rCBF <30%) or DWI if quantitative software tools are available (neither test is mandatory for study)

Exclusion Criteria

NIHSS ≥6
Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH)
Any imaging findings suggestive of futile recanalization in the judgment of the local investigator
High degree of suspicion of intracranial arterial disease (ICAD), such as evidence of multifocal ICAD
Premorbid disability (mRS ≥3)
Inability to randomize within 8 hours of last known well
Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
Baseline blood glucose of <50 mg/dL (2.78 mmol) or >400 mg/dL (22.20 mmol)
Known coagulation disorders as defined as platelet count <100,000/uL
Known renal failure as defined as serum creatinine levels > 3.0 mg/dL
Presumed septic embolus or suspicion of bacterial endocarditis
Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the subject if an endovascular procedure was performed.
Participation in another investigational treatment study in the previous 30 days
Intubation and mechanical ventilation prior to study enrollment is medically indicated
History of drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
Site investigator does not have equipoise towards the ideal treatment concept (thrombectomy vs. best medical management)
Known pregnancy
Prisoner or incarceration
Known acute symptomatic COVID-19 infection

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immediate mechanical thrombectomy(iMT)	Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device	Treatment initiation within 8 hours of symptom onset. Arterial puncture and revascularization will be performed using EmboTrap II Retriever. The procedure will be completed within two hours of arterial access.
Initial medical management (iMM)	Initial medical management (iMM)	Standard medical therapy based on current AHA (American Heart Association) guidelines. Rescue mechanical thrombectomy (rMT) is allowed for patients initially assigned to iMM if they suffer major neurological worsening that clearly requires an intra-arterial intervention in the judgment of the treating team.

Primary Outcome Measures

Name	Time	Method
Symptomatic intracranial hemorrhage (sICH) within 36 hours comparing the two treatment arms	36 hours	Symptomatic intracranial hemorrhage (sICH) within 36 hours post treatment imaging scan, using SITS-MOST criteria, consisting of the presence of parenchymal hematoma type 2 (PH2) on neuroimaging associated with 4-point decline in NIHSS from baseline to 24 hours
Symptomatic intracerebral hemorrhage within 96 hours comparing the two treatment arms	96 hours	Symptomatic intracerebral hemorrhage is defined as local or remote parenchymal hemorrhage type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage within 96 hours post-randomization, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 hour, or leading to death
90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (Ordinal Shift Analysis).	90-day	The distribution of the modified Rankin Scale (mRS) is assessed by structured assessment. The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.

Secondary Outcome Measures

Name	Time	Method
Number of patients with excellent outcome comparing the two treatment arms arms	90-day	Excellent outcome is defined by a score 0-1 on the 90-day mRS. The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.
Shift in distribution of the 90-day mRS with levels 5-6 combined (0;1;2;3;4;5-6) comparing the two treatment arms	90-day	The distribution of the 90-day modified Rankin Scale (mRS) with levels 5-6 combined (0;1;2;3;4;5-6) is assessed by structured assessment. The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.
Health-related quality of life EQ-5D score comparing the two treatment arms	90-day	EQ-5D is a standardized instrument measuring health-related quality of life. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number.
Infarct volume	24 hours post randomization	Infarct volume is a direct measurement of one of the final pathologic steps leading to the clinical deficits caused by an ischemic stroke.Final infarct volume derived from MR imaging.
Self-reported mental and physical health PROMIS Global-10 score	90-day	Mental and physical health will be assessed using PROMIS Global-10. The PROMIS Global-10 short form consists of 10 items that assess general domains of health and functioning including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life.Scores are converted to a T-Score metric.
Instrumental Activities of Daily Living (IADL)	90-day	Instrumental Activities of Daily Living (IADLs) are activities related to independent living. The IADL scale covers eight functional domains: using the telephone, shopping, food preparation, housekeeping, laundry, transport, medication, and finances. Participants are scored according to their highest level of functioning in categories, and summary score ranges from 0 (low function, dependent) to 8 (high function, independent).
Number of patients with good outcome comparing the two treatment arms	90-day	Good outcome is defined by a score of 0-2 on the 90-day mRS. The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.
Number of patients with early Neurologic Deterioration (END) comparing the two treatment arms	24 hours post randomization	Early Neurologic Deterioration (END) is defined as an increase in NIHSS of ≥4 points. NIH Stroke Scale/Score (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items.
Self-reported PROMIS Fatigue score	90-day	The PROMIS Fatigue assesses a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. Each question has five response options ranging in value from one to five.To find the total raw score, values of the response to each question will be summed up. Total raw score will be transformed into a T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person with a T-score of 40 is one SD below the mean.
Number of patients with intracranial hemorrhages using the Heidelberg Bleeding definition comparing the two treatment arms	90-day	Intracranial hemorrhages will be defined using the Heidelberg Bleeding criteria.
Mortality rate within 90 days comparing the two treatment arms	90-day	Mortality rate will be calculated.

Trial Locations

Locations (47): Indiana University
🇺🇸
Bloomington, Indiana, United States
Baptist Health Lexington
🇺🇸
Lexington, Kentucky, United States
Texas Tech University Health Sciences Center at El Paso
🇺🇸
El Paso, Texas, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Advocate Aurora Health
🇺🇸
Downers Grove, Illinois, United States
Institute of Neuroradiology, University Hospital Frankfurt
🇩🇪
Frankfurt Am Main, Hessen, Germany
Universitätsklinikum Essen
🇩🇪
Essen, Nordrhein-Westfalen, Germany
McLaren Health Care Corporation
🇺🇸
Grand Blanc, Michigan, United States
University at Buffalo Neurosurgery/ Kaleida Health
🇺🇸
Buffalo, New York, United States
Klinikum Osnabrueck, Department of Neurology
🇩🇪
Osnabrück, Niedersachsen, Germany
The Ottawa Hospital Civic Campus
🇨🇦
Ottawa, Ontario, Canada
London Health Sciences Centre
🇨🇦
London, Ontario, Canada
Universitätsmedizin Göttingen
🇩🇪
Göttingen, Niedersachsen, Germany
University Hospital Carl Gustav Carus Dresden Dresden, Department of Neurology
🇩🇪
Dresden, Sachsen, Germany
Providence Little Company of Mary Medical Center
🇺🇸
Torrance, California, United States
Grady Health System (non-CRN)
🇺🇸
Atlanta, Georgia, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Baptist Health Jacksonville FL
🇺🇸
Jacksonville, Florida, United States
Rush University Medical Center: University Neurosurgery
🇺🇸
Chicago, Illinois, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
University of Massachusetts Medical Center
🇺🇸
Worcester, Massachusetts, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Riverside Medical Center, OhioHealth Research Institute
🇺🇸
Columbus, Ohio, United States
VHS-Harlingen Hospital Company dba Valley Baptist Medical Center-Harlingen
🇺🇸
Harlingen, Texas, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Trillium Health Partners
🇨🇦
Mississauga, Ontario, Canada
University of Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Ludwig Maximilian University, Department of Neurology
🇩🇪
München, Bayern, Germany
University Hospital Schleswig-Holstein, Campus Kiel
🇩🇪
Kiel, Schleswig-Holstein, Germany
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Ohio State Wexner Medical Center
🇺🇸
Columbus, Ohio, United States
Gesundheit Nord Klinikum Bremen-Mitte
🇩🇪
Bremen, Germany
Michigan Medicine Comprehensive Stroke Center
🇺🇸
Ann Arbor, Michigan, United States
Prisma Health-Upstate
🇺🇸
Greenville, South Carolina, United States
University of Calgary and Foothills Medical Centre
🇨🇦
Calgary, Alberta, Canada
Montreal Neurological Institute and Hospital
🇨🇦
Montréal, Quebec, Canada
Universitätsklinikum Freiburg, Klinik für Neurologie
🇩🇪
Freiburg im Breisgau, Baden-Württemberg, Germany
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
University of Saskatchewan
🇨🇦
Saskatoon, Saskatchewan, Canada
JFK Neurosciences Center
🇺🇸
Edison, New Jersey, United States
Semmes Murphey Foundation
🇺🇸
Memphis, Tennessee, United States
Universitäts Klinikum Heidelberg
🇩🇪
Heidelberg, Baden-Württemberg, Germany
Thomas Jefferson University
🇺🇸
Woodbury, New Jersey, United States

Endovascular Therapy for Low NIHSS Ischemic Strokes

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