Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3

Overview

About this study

This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment) or ICA occlusion who can be randomized and have endovascular treatment initiated between 6-16 hours after last seen well.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Clinical Inclusion Criteria:

  1. Signs & symptoms consistent w/ the diagnosis of acute anterior circulation ischemic stroke
  2. Age 18-90 years
  3. Baseline NIHSSS is ≥ 6 and remains ≥6 immediately prior to randomization
  4. Endovascular treatment can be initiated (femoral puncture) between 6 and 16 hours of stroke onset. Stroke onset is defined as the time the patient was last known to be at their neurologic baseline (wake-up strokes are eligible if they meet the above time limits).
  5. modified Rankin Scale less than or equal to 2 prior to qualifying stroke (functionally independent for all ADLs)
  6. Patient/Legally Authorized Representative has signed the Informed Consent form.

Clinical Exclusion Criteria:

  1. Other serious, advanced, or terminal illness (investigator judgment) or life expectancy is less than 6 months.
  2. Pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
  3. Pregnant
  4. Unable to undergo a contrast brain perfusion scan with either MRI or CT
  5. Known allergy to iodine that precludes an endovascular procedure
  6. Treated with tPA >4.5 hours after time last known well
  7. Treated with tPA 3-4.5 hours after last known well AND any of the following; age >80, current anticoagulant use, history of diabetes or prior stroke, NIHSS >25
  8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR > 3 (recent use of one of the new oral anticoagulants is not an exclusion if estimated GFR > 30 ml/min).
  9. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
  10. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)
  11. Baseline platelet count < 50,000/uL
  12. Severe, sustained hypertension (Systolic BP >185 mmHg or Diastolic BP >110 mmHg)
  13. Current participation in another investigational drug or device study
  14. Presumed septic embolus; suspicion of bacterial endocarditis
  15. Clot retrieval attempted using a neurothrombectomy device prior to 6 hrs from symptom onset
  16. 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.

Neuroimaging Inclusion Criteria:

  1. ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA or CTA

    AND

  2. Target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml, mismatch ratio is >/= 1.8 and mismatch volume* is >/= 15 ml)

Alternative neuroimaging inclusion criteria (if perfusion imaging or CTA/MRA is technically inadequate):

A) If CTA (or MRA) is technically inadequate:

Tmax>6s perfusion deficit consistent with an ICA or MCA-M1 occlusion AND Target Mismatch Profile (ischemic core volume is < 70 ml, mismatch ratio is >1.8 and mismatch volume is >15 ml as determined by RAPID software)

B) If MRP is technically inadequate:

ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI) AND DWI lesion volume < 25 ml

C) If CTP is technically inadequate:

Patient can be screened with MRI and randomized if neuroimaging criteria are met.

Neuroimaging Exclusion Criteria:

  1. ASPECTS score <6 on non-contrast CT (if patient is enrolled based on CT perfusion criteria)
  2. Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
  3. Significant mass effect with midline shift
  4. Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
  5. Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device
  6. Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

James Klaas, M.D.

Closed for enrollment

More information

Publications

  • Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0-2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test). Read More on PubMed
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CLS-20325245

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