Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)

September 6, 2023 updated by: Raul Gomes Nogueira, Emory University
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Alberta
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • Not yet recruiting
        • University of Manitoba
        • Contact:
        • Contact:
    • Ontario
      • London, Ontario, Canada, N6A 5A5
      • Mississauga, Ontario, Canada, L5B 2P7
        • Withdrawn
        • Trillium Health Partners
      • Ottawa, Ontario, Canada, K1Y 4E9
        • Not yet recruiting
        • The Ottawa Hospital Civic Campus
        • Contact:
          • Dar Dowlatshahi, MD
          • Phone Number: 16449 (613) 798-5555
          • Email: ddowlat@toh.ca
        • Contact:
      • Toronto, Ontario, Canada, M4N 3M5
        • Withdrawn
        • Sunnybrook Health Sciences Centre
    • Quebec
      • Montréal, Quebec, Canada, H3A 2B4
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
  • Germany
    • Baden-Württemberg
      • Freiburg im Breisgau, Baden-Württemberg, Germany, 79106
      • Heidelberg, Baden-Württemberg, Germany, 69120
    • Bayern
      • München, Bayern, Germany, 81377
        • Not yet recruiting
        • Ludwig Maximilian University, Department of Neurology
        • Contact:
    • Hessen
      • Frankfurt Am Main, Hessen, Germany, 60528
        • Not yet recruiting
        • Institute of Neuroradiology, University Hospital Frankfurt
        • Contact:
    • Niedersachsen
      • Göttingen, Niedersachsen, Germany, 37075
      • Osnabrück, Niedersachsen, Germany, 49076
        • Not yet recruiting
        • Klinikum Osnabrueck, Department of Neurology
        • Contact:
    • Nordrhein-Westfalen
      • Essen, Nordrhein-Westfalen, Germany, 45147
        • Not yet recruiting
        • Universitätsklinikum Essen
        • Contact:
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Not yet recruiting
        • University Hospital Carl Gustav Carus Dresden Dresden, Department of Neurology
        • Contact:
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Not yet recruiting
        • University Hospital Schleswig-Holstein, Campus Kiel
        • Contact:
  • United States
    • California
      • Torrance, California, United States, 90503
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Baptist Health Jacksonville FL
        • Contact:
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine
        • Contact:
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Grady Health System (non-CRN)
        • Contact:
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60612
      • Downers Grove, Illinois, United States, 60068
    • Indiana
      • Bloomington, Indiana, United States, 47401
        • Recruiting
        • Indiana University
        • Contact:
          • Kaustubh Limaye, MD
          • Phone Number: 317-963-7505
          • Email: klimaye@iu.edu
    • Iowa
      • Iowa City, Iowa, United States, 52241
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Not yet recruiting
        • Baptist Health Lexington
        • Contact:
    • Massachusetts
      • Worcester, Massachusetts, United States, 01605
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Withdrawn
        • Michigan Medicine Comprehensive Stroke Center
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Contact:
        • Contact:
      • Grand Blanc, Michigan, United States, 48439
        • Not yet recruiting
        • McLaren Health Care Corporation
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Contact:
    • New Jersey
      • Edison, New Jersey, United States, 08820
        • Not yet recruiting
        • JFK Neurosciences Center
        • Contact:
      • Woodbury, New Jersey, United States, 08096
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Albany Medical Center
        • Contact:
      • Buffalo, New York, United States, 14203
        • Recruiting
        • University at Buffalo Neurosurgery/ Kaleida Health
        • Contact:
        • Contact:
      • New York, New York, United States, 10029
    • Ohio
      • Cincinnati, Ohio, United States, 45219
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Contact:
      • Columbus, Ohio, United States, 43210
      • Columbus, Ohio, United States, 43214
    • Oregon
      • Portland, Oregon, United States, 97239
        • Withdrawn
        • Oregon Health & Science University
    • South Carolina
      • Greenville, South Carolina, United States, 29601
    • Tennessee
      • Memphis, Tennessee, United States, 38120
    • Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: 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.

Other Names:
  • EmboTrap III
Active Comparator: 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.
Combination product: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (Ordinal Shift Analysis).
Time Frame: 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.
90-day
Symptomatic intracranial hemorrhage (sICH) within 36 hours comparing the two treatment arms
Time Frame: 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
36 hours
Symptomatic intracerebral hemorrhage within 96 hours comparing the two treatment arms
Time Frame: 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
96 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
90-day
Number of patients with good outcome comparing the two treatment arms
Time Frame: 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.
90-day
Number of patients with excellent outcome comparing the two treatment arms arms
Time Frame: 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.
90-day
Number of patients with early Neurologic Deterioration (END) comparing the two treatment arms
Time Frame: 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.
24 hours post randomization
Health-related quality of life EQ-5D score comparing the two treatment arms
Time Frame: 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.
90-day
Infarct volume
Time Frame: 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.
24 hours post randomization
Self-reported mental and physical health PROMIS Global-10 score
Time Frame: 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.
90-day
Self-reported PROMIS Fatigue score
Time Frame: 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.
90-day
Number of patients with intracranial hemorrhages using the Heidelberg Bleeding definition comparing the two treatment arms
Time Frame: 90-day
Intracranial hemorrhages will be defined using the Heidelberg Bleeding criteria.
90-day
Mortality rate within 90 days comparing the two treatment arms
Time Frame: 90-day
Mortality rate will be calculated.
90-day
Instrumental Activities of Daily Living (IADL)
Time Frame: 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).
90-day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

University of Calgary
Children's Hospital Medical Center, Cincinnati
Heidelberg University
University of Cincinnati

Investigators

  • Principal Investigator: Raul G Nogueira, MD, Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 5, 2020

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

November 15, 2019

First Submitted That Met QC Criteria

November 15, 2019

First Posted (Actual)

November 19, 2019

Study Record Updates

Last Update Posted (Actual)

September 8, 2023

Last Update Submitted That Met QC Criteria

September 6, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00107210

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in this article will be available after de-identification and in accordance with applicable laws and regulations. Other limited data sets may be provided as governed by ENDOLOW Publications SOP and in accordance with ICMJE.

IPD Sharing Time Frame

Data will become available beginning 1 year after publication of the primary analysis.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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