MR RESCUE: Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy 3.1b

Objectives

  1. To test the hypothesis that the presence of substantial ischemic penumbral tissue visualized on multimodal imaging (MRI or CT) predicts patients most likely to respond to mechanical embolectomy for treatment of acute ischemic stroke due to a large vessel occlusion up to 8 hours from symptom onset.

This hypothesis will be tested by analyzing whether pretreatment imaging pattern has a significant interaction with treatment as a determinant of functional outcome. The primary study endpoint employed to test this hypothesis will be the distribution of scores on the modified Rankin Scale measure of global handicap assessed 90 days post-stroke.

  1. To test the nested hypothesis that patients with a penumbral imaging pattern have improved functional outcome when treated with mechanical embolectomy vs. standard medical care.

The primary study endpoint employed to test this hypothesis in a treatment superiority analysis will be the distribution of scores on the modified Rankin Scale measure of global handicap assessed 90 days post-stroke between the embolectomy and control groups among patients with a penumbral imaging pattern at entry.

  1. To test the nested hypothesis that patients without a penumbral imaging pattern do not have improved functional outcomes when treated with mechanical embolectomy vs. standard medical management, and to determine in an exploratory manner if there is a signal of potential moderate efficacy or harm.

The primary study endpoint employed to test this hypothesis in a treatment equivalency analysis will be the distribution of scores on the modified Rankin Scale measure of global handicap assessed 90 days post-stroke between the embolectomy and control groups among patients with a non-penumbral imaging pattern at entry.

  1. To test the hypothesis that patients treated with mechanical embolectomy have improved functional outcome vs. standard medical management (to be tested if the primary hypothesis of interaction is negative). The endpoint employed to test this hypothesis in a treatment superiority analysis will be the distribution of scores on the modified Rankin Scale measure of global handicap assessed 90 days post-stroke between the embolectomy and control groups among patients.

Study Design

Adult male or female patients, presenting within 8 hours of symptoms onset and meeting inclusion criteria at each of the study sites will be assessed for possible enrollment into the study.

Patients will be screened for eligibility by a study investigator as soon as possible after arrival to the hospital or, for patients who have a stroke in the hospital, as soon as possible after onset of symptoms. The screening process will involve the following:

  • Medical history and physical examination
  • Premorbid mRS and BI
  • Scoring of neurologic deficit, using the NIHSS
  • Pretreatment multimodal MRI or multimodal CT confirming acute cerebral ischemia with a large vessel occlusion on MR or CT angiography
  • Laboratory tests (hemoglobin, hematocrit, white blood cell count, platelet count, INR, activated partial thromboplastin time, prothrombin time, serum creatinine, blood glucose, pregnancy test for women of childbearing age and EKG)

Once inclusion/exclusion criteria are satisfied, the imaging data will be transferred to the dedicated MR RESCUE computer for image post-processing. The computer program will automatically generate a 4 digit randomization code. The investigator must call the MR RESCUE on-call physician prior to study enrollment – the name and contact number of the MR RESCUE on call physician can be located on the MR RESCUE website: The patient will then be enrolled employing explicit consent procedures. The consent provider will be the patient if he or she is competent or the patient's legally authorized representative if the patient is not competent. Once informed consent has been obtained, the study investigator enters the patient’s data into the dedicated MR RESCUE website: The investigator must also enter the code for penumbral pattern. Based on this information, the website will generate a randomization number and treatment assignment for the patient.

Treatment

If randomized to embolectomy therapy, the patient will be immediately transported to the neurointerventional angiographic suite following the MRI or CT for mechanical embolectomy

Patients randomized to the control group will receive best conventional medical therapy for acute ischemic stroke as determined by the attending stroke physician.

Number of Subjects: Total up to 120 subjects will be enrolled.

Inclusion/Exclusion Criteria

Inclusion Criteria:

  1. New focal disabling neurologic deficit consistent with acute cerebral ischemia (NIHSS  6 with at least six points attributed to current stroke)
  2. Age  18 ≤ 85
  3. Clot retrieval procedure can be initiated within 8 hours from onset
  4. Large vessel proximal anterior circulation occlusion on MR or CT angiography (internal carotid, M1 or M2 MCA)
  5. Signed informed consent obtained from the patient or patient’s legally authorized representative
  6. Pretreatment multimodal MRI or CT performed according to MR RESCUE protocol
  7. Premorbid modified Rankin score of 0-2
  8. Allowed but not required: patients treated with IV tPA up to 4.5 hours from symptom onset with persistent target occlusion on post-treatment MR RESCUE MR or CT protocol performed at the completion of drug infusion (Note: Rapidly improving neurological signs prior to randomization is an exclusion).

Exclusion Criteria:

  1. NIHSS  30
  2. Acute intracranial hemorrhage
  3. Coma
  4. Rapidly improving neurological signs prior to randomization
  5. Pre-existing medical, neurological or psychiatric disease that would confound the neurological, functional, or imaging evaluations
  6. Pregnancy
  7. Known allergy to iodine previously refractory to pretreatment medications
  8. Current participation in another experimental treatment protocol
  9. Contrast-Enhanced Neck MRA or CTA suggests proximal ICA occlusion, proximal carotid stenosis > 67%, or dissection
  10. INR > 3.0
  11. PTT > 3 x Normal
  12. Imaging data cannot be processed by MR RESCUE computer
  13. Renal failure: serum creatinine > 2.0 or GFR < 30

MRI Exclusion Criteria:

Contraindication to MRI (pacemaker etc)

CT Exclusion Criteria

Contraindication to iodinated contrast**

**Examples of possible iodinated contrast contraindications include:

  • Hyperthyroidism
  • History of severe allergic reaction to iodinated contrast material
  • History of severe kidney disease as an adult, including tumor or transplant surgery, or family history of kidney failure
  • Paraproteinemia syndromes or multiple myeloma
  • Collagen vascular disease
  • Severe cardiac insufficiency
  • Severely compromised liver function
  • Current therapy with metformin, aminoglycosides