Endovascular Therapy for Low NIHSS Ischemic Strokes

NCT ID: NCT04167527

Last Updated: 2025-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

143 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-05

Study Completion Date

2025-09-30

Brief Summary

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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

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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).

Conditions

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Cerebral Ischemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Immediate mechanical thrombectomy(iMT)

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.

Group Type EXPERIMENTAL

Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device

Intervention Type DEVICE

Treatment initiation is defined as the date and time of arterial puncture. Femoral artery puncture will occur within 45 minutes of randomization and no longer than 90 minutes after the completion of the qualifying imaging. It must occur before 8 hours since the subject was last known well.The initial procedure will be performed using only the EmboTrap II Retriever for the first two passes, and a third pass is encouraged. Date and time of arterial puncture, revascularization, and procedure end will be recorded. It is expected that the interventional procedure will be completed within two hours of arterial access.

All subjects, regardless of randomization arm, will receive best medical management based on current American Heart Association, Canadian, or European guidelines according to their geographic location.

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.

Group Type ACTIVE_COMPARATOR

Initial medical management (iMM)

Intervention Type COMBINATION_PRODUCT

Patients will receive standard medical therapy based on current AHA guidelines. For patients who are treated with intravenous tissue plasminogen activator (rtPA), the sites' post-rtPA protocol will be followed. 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.

All subjects, regardless of randomization arm, will receive best medical management based on current American Heart Association, Canadian, or European guidelines according to their geographic location.

Interventions

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Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device

Treatment initiation is defined as the date and time of arterial puncture. Femoral artery puncture will occur within 45 minutes of randomization and no longer than 90 minutes after the completion of the qualifying imaging. It must occur before 8 hours since the subject was last known well.The initial procedure will be performed using only the EmboTrap II Retriever for the first two passes, and a third pass is encouraged. Date and time of arterial puncture, revascularization, and procedure end will be recorded. It is expected that the interventional procedure will be completed within two hours of arterial access.

All subjects, regardless of randomization arm, will receive best medical management based on current American Heart Association, Canadian, or European guidelines according to their geographic location.

Intervention Type DEVICE

Initial medical management (iMM)

Patients will receive standard medical therapy based on current AHA guidelines. For patients who are treated with intravenous tissue plasminogen activator (rtPA), the sites' post-rtPA protocol will be followed. 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.

All subjects, regardless of randomization arm, will receive best medical management based on current American Heart Association, Canadian, or European guidelines according to their geographic location.

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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EmboTrap III

Eligibility Criteria

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Inclusion Criteria

1. Age 18 years or older
2. Acute ischemic stroke based on clinical diagnosis (NIHSS 0-5) and presence of an objective neurological deficit
3. Patients eligible for intravenous rt-PA should receive this therapy as soon as possible and no later than 4.5 hours from symptom onset
4. 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
5. 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

1. NIHSS ≥6
2. Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH)
3. Any imaging findings suggestive of futile recanalization in the judgment of the local investigator
4. High degree of suspicion of intracranial arterial disease (ICAD), such as evidence of multifocal ICAD
5. Premorbid disability (mRS ≥3)
6. Inability to randomize within 8 hours of last known well
7. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
8. Baseline blood glucose of \<50 mg/dL (2.78 mmol) or \>400 mg/dL (22.20 mmol)
9. Known coagulation disorders as defined as platelet count \<100,000/uL
10. Known renal failure as defined as serum creatinine levels \> 3.0 mg/dL
11. Presumed septic embolus or suspicion of bacterial endocarditis
12. 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.
13. Participation in another investigational treatment study in the previous 30 days
14. Intubation and mechanical ventilation prior to study enrollment is medically indicated
15. History of drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
16. Site investigator does not have equipoise towards the ideal treatment concept (thrombectomy vs. best medical management)
17. Known pregnancy
18. Prisoner or incarceration
19. Known acute symptomatic COVID-19 infection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Calgary

OTHER

Sponsor Role collaborator

University of Cincinnati

OTHER

Sponsor Role collaborator

Heidelberg University

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Raul Gomes Nogueira

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Raul G Nogueira, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Providence Little Company of Mary Medical Center

Torrance, California, United States

Site Status

Baptist Health Jacksonville FL

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Grady Health System (non-CRN)

Atlanta, Georgia, United States

Site Status

Rush University Medical Center: University Neurosurgery

Chicago, Illinois, United States

Site Status

Advocate Aurora Health

Downers Grove, Illinois, United States

Site Status

Indiana University

Bloomington, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status

University of Massachusetts Medical Center

Worcester, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

McLaren Health Care Corporation

Grand Blanc, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

JFK Neurosciences Center

Edison, New Jersey, United States

Site Status

Thomas Jefferson University

Woodbury, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

University at Buffalo Neurosurgery/ Kaleida Health

Buffalo, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State Wexner Medical Center

Columbus, Ohio, United States

Site Status

Riverside Medical Center, OhioHealth Research Institute

Columbus, Ohio, United States

Site Status

Prisma Health-Upstate

Greenville, South Carolina, United States

Site Status

Semmes Murphey Foundation

Memphis, Tennessee, United States

Site Status

Texas Tech University Health Sciences Center at El Paso

El Paso, Texas, United States

Site Status

VHS-Harlingen Hospital Company dba Valley Baptist Medical Center-Harlingen

Harlingen, Texas, United States

Site Status

University of Calgary and Foothills Medical Centre

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

University of Manitoba

Winnipeg, Manitoba, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

Site Status

University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Universitäts Klinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Ludwig Maximilian University, Department of Neurology

München, Bavaria, Germany

Site Status

Countries

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United States Canada Germany

References

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Seners P, Cereda CW. Thrombectomy in Stroke With a Large Vessel Occlusion and Mild Symptoms: "Striving to Better, Oft We Mar What's Well?". Stroke. 2023 Sep;54(9):2276-2278. doi: 10.1161/STROKEAHA.123.044205. Epub 2023 Aug 1. No abstract available.

Reference Type DERIVED
PMID: 37526012 (View on PubMed)

Feil K, Matusevicius M, Herzberg M, Tiedt S, Kupper C, Wischmann J, Schonecker S, Mengel A, Sartor-Pfeiffer J, Berger K, Dimitriadis K, Liebig T, Dieterich M, Mazya M, Ahmed N, Kellert L. Minor stroke in large vessel occlusion: A matched analysis of patients from the German Stroke Registry-Endovascular Treatment (GSR-ET) and patients from the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). Eur J Neurol. 2022 Jun;29(6):1619-1629. doi: 10.1111/ene.15272. Epub 2022 Feb 19.

Reference Type DERIVED
PMID: 35122371 (View on PubMed)

Other Identifiers

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IRB00107210

Identifier Type: -

Identifier Source: org_study_id

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