Endovascular Therapy for Low NIHSS Ischemic Strokes

Cerebral Ischemia Clinical Trial

— ENDOLOW  

Official title:

Endovascular Therapy for Low NIHSS Ischemic Strokes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04167527
• Other study ID #: IRB00107210
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 5, 2020
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Emory University
• Contact: David Wright, MD
• Phone: 404-778-1709
• Email: dwwrigh[@]emory.edu; endolow[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Ischemia
• Cerebral Infarction
• Cerebral Ischemia
• Ischemic Stroke

Intervention

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.

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.

Locations

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

Sponsors (5)

Lead Sponsor	Collaborator
Emory University	Children's Hospital Medical Center, Cincinnati, Heidelberg University, University of Calgary, University of Cincinnati

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

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