Clinical trial NCT04167527: Endovascular Therapy for Low NIHSS Ischemic Strokes
Official title: Endovascular Therapy for Low NIHSS Ischemic Strokes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Cerebral Ischemia
Keywords: Immediate Mechanical Thrombectomy
Initial medical management
Large vessel occlusion
Efficacy
Safety
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: University of Calgary
name: University of Cincinnati
name: Heidelberg University
name: Children's Hospital Medical Center, Cincinnati
First posted: 2019-11-19
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (Ordinal Shift Analysis).
timeFrame: 90-day
measure: Symptomatic intracranial hemorrhage (sICH) within 36 hours comparing the two treatment arms
timeFrame: 36 hours
measure: Symptomatic intracerebral hemorrhage within 96 hours comparing the two treatment arms
timeFrame: 96 hours
Secondary outcomes:
measure: 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
timeFrame: 90-day
measure: Number of patients with good outcome comparing the two treatment arms
timeFrame: 90-day
measure: Number of patients with excellent outcome comparing the two treatment arms arms
timeFrame: 90-day
measure: Number of patients with early Neurologic Deterioration (END) comparing the two treatment arms
timeFrame: 24 hours post randomization
measure: Health-related quality of life EQ-5D score comparing the two treatment arms
timeFrame: 90-day
measure: Infarct volume
timeFrame: 24 hours post randomization
measure: Self-reported mental and physical health PROMIS Global-10 score
timeFrame: 90-day
measure: Self-reported PROMIS Fatigue score
timeFrame: 90-day
measure: Number of patients with intracranial hemorrhages using the Heidelberg Bleeding definition comparing the two treatment arms
timeFrame: 90-day
measure: Mortality rate within 90 days comparing the two treatment arms
timeFrame: 90-day
measure: Instrumental Activities of Daily Living (IADL)
timeFrame: 90-day
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Providence Little Company of Mary Medical Center
state: California
city: Jacksonville
country: United States
facility: Baptist Health Jacksonville FL
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Grady Health System (non-CRN)
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center: University Neurosurgery
state: Illinois
city: Downers Grove
country: United States
facility: Advocate Aurora Health
state: Illinois
city: Bloomington
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Worcester
country: United States
facility: University of Massachusetts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Blanc
country: United States
facility: McLaren Health Care Corporation
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Edison
country: United States
facility: JFK Neurosciences Center
state: New Jersey
city: Woodbury
country: United States
facility: Thomas Jefferson University
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Buffalo
country: United States
facility: University at Buffalo Neurosurgery/ Kaleida Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Medical Center, OhioHealth Research Institute
state: Ohio
city: Greenville
country: United States
facility: Prisma Health-Upstate
state: South Carolina
city: Memphis
country: United States
facility: Semmes Murphey Foundation
state: Tennessee
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center at El Paso
state: Texas
city: Harlingen
country: United States
facility: VHS-Harlingen Hospital Company dba Valley Baptist Medical Center-Harlingen
state: Texas
city: Calgary
country: Canada
facility: University of Calgary and Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
city: Heidelberg
country: Germany
facility: Universitäts Klinikum Heidelberg
state: Baden-Württemberg
city: München
country: Germany
facility: Ludwig Maximilian University, Department of Neurology
state: Bayern
Study officials:
affiliation: Emory University
name: Raul G Nogueira, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.