Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)

Emory University

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Cerebral Ischemia

Treatments: Device: Immediate mechanical thrombectomy(iMT) using EmboTrap Revascularization Device; Combination Product: Initial medical management (iMM)

Study type: Interventional

Funder types: Other

Identifiers

NCT04167527

IRB00107210

Details and patient eligibility

About

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).

Full 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).

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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200 participants in 2 patient groups

Immediate mechanical thrombectomy(iMT)

Experimental group

Description:

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.

Treatment:

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

Initial medical management (iMM)

Active Comparator group

Description:

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.

Treatment:

Combination Product: Initial medical management (iMM)