Endovascular Therapy for Low NIHSS Ischemic Strokes

NCT04167527 | Active Not Recruiting Phase 2 DMC FDA Device

• 1 other identifier: IRB00107210
• Study Type: interventional
• Target: 143
• Locations: 3 countries
• Sites: 34

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).

Conditions

Cerebral Ischemia

Keywords

Immediate Mechanical Thrombectomy; Initial medical management; Large vessel occlusion; Efficacy; Safety

Outcome Measures

Primary Outcomes (3)

• 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (Ordinal Shift Analysis).

  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.

  90-day

• Symptomatic intracranial hemorrhage (sICH) within 36 hours comparing the two treatment arms

  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

  36 hours

• Symptomatic intracerebral hemorrhage within 96 hours comparing the two treatment arms

  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

  96 hours

Secondary Outcomes (11)

• 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

• Number of patients with good outcome comparing the two treatment arms

  90-day

• Number of patients with excellent outcome comparing the two treatment arms arms

  90-day

• Number of patients with early Neurologic Deterioration (END) comparing the two treatment arms

  24 hours post randomization

• Health-related quality of life EQ-5D score comparing the two treatment arms

  90-day

Study Arms (2)

Immediate mechanical thrombectomy(iMT)

EXPERIMENTAL

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.

Device: Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device

Initial medical management (iMM)

ACTIVE COMPARATOR

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.

Combination Product: Initial medical management (iMM)

Interventions

Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device 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.

Also known as: EmboTrap III

Immediate mechanical thrombectomy(iMT)

Initial medical management (iMM) 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.

Initial medical management (iMM)

Eligibility Criteria

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

You may qualify if:

• 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:
• 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).
• 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:
• Baseline ASPECTS ≥6 on non-contrast CT (NCCT), or
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• University of Calgary: collaborator
• University of Cincinnati: collaborator
• Heidelberg University: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (34)

Providence Little Company of Mary Medical Center

Torrance, California, 90503, United States

Location

Baptist Health Jacksonville FL

Jacksonville, Florida, 32207, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Grady Health System (non-CRN)

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center: University Neurosurgery

Chicago, Illinois, 60612, United States

Location

Advocate Aurora Health

Downers Grove, Illinois, 60068, United States

Location

Indiana University

Bloomington, Indiana, 47401, United States

Location

University of Iowa

Iowa City, Iowa, 52241, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

University of Massachusetts Medical Center

Worcester, Massachusetts, 01605, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

McLaren Health Care Corporation

Grand Blanc, Michigan, 48439, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

JFK Neurosciences Center

Edison, New Jersey, 08820, United States

Location

Thomas Jefferson University

Woodbury, New Jersey, 08096, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

University at Buffalo Neurosurgery/ Kaleida Health

Buffalo, New York, 14203, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Riverside Medical Center, OhioHealth Research Institute

Columbus, Ohio, 43214, United States

Location

Prisma Health-Upstate

Greenville, South Carolina, 29601, United States

Location

Semmes Murphey Foundation

Memphis, Tennessee, 38120, United States

Location

Texas Tech University Health Sciences Center at El Paso

El Paso, Texas, 79905, United States

Location

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

Harlingen, Texas, 78550, United States

Location

University of Calgary and Foothills Medical Centre

Calgary, Alberta, T2N 5A6, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E 3P4, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

University of Saskatchewan

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Universitäts Klinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Ludwig Maximilian University, Department of Neurology

München, Bavaria, 81377, Germany

Location

Related Publications (2)

• 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.

  PMID: 37526012 DERIVED

• 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.

  PMID: 35122371 DERIVED

MeSH Terms

Conditions

Brain Ischemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Raul G Nogueira, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: November 15, 2019
• First Posted: November 19, 2019
• Study Start: September 5, 2020
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will become available beginning 1 year after publication of the primary analysis.
• Access Criteria: After primary analysis publication, site investigators will have the opportunity to contribute to secondary, tertiary and quaternary analysis of the data and publication. Additionally, after 1 year, non-investigator researchers may submit requests to the publications committee for additional analysis after providing a methodologically sound proposal. Proposals can be sent to ENDOLOW-CCC@emory.edu. Data Transfer Agreements may apply.

Locations

US (26); CA (6); DE (2)