Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of treating acute ischemic stroke with mechanical embolectomy using the Merci Retriever or the Penumbra System within 8 hours of symptom onset to standard medical treatment, and to identify people who might benefit from mechanical embolectomy by the appearance of stroke on multimodal computerized tomography (CT) or magnetic resonance (MR) imaging.

Detailed Description
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Stroke most commonly occurs when there is a blockage of blood flow to one of the arteries in the brain. The blockage is often caused by a clot. There is currently only one FDA-approved stroke treatment. However, only 2 percent of ischemic stroke patients receive this treatment because it must be given within 4.5 hours of the stroke onset. There is an overwhelming need for new treatments that extend the time window to treatment since most individuals with stroke arrive at the hospital after the 4.5-hour time window. Two of the most promising new devices are the Merci Retriever, a tiny corkscrew device, and the Penumbra System, an aspiration device. Both are designed to remove clots from arteries and thereby restore blood flow to the brain. The primary purpose of this study is to compare the effectiveness of treatment with the Merci Retriever or Penumbra System within 8 hours of symptom onset to standard medical treatment, and to identify people who might benefit from the devices by the appearance of the stroke on multimodal computerized tomography (CT) or magnetic resonance imaging (MRI). Previous testing has determined that the use of the Merci Retriever is successful in opening up blocked blood vessels in approximately ½ of the individuals in whom it is used, and the Penumbra System is successful in opening up blocked blood vessels in approximately 80% of the individuals in whom it is used. A total of 120 participants from approximately 30 different medical centers will be enrolled into this study. Participants will be randomized to either receive treatment by mechanical embolectomy with the Merci Retriever or Penumbra System and standard medical care or treatment with standard medical care alone. Standard care for stroke patients may include intravenous fluid, careful regulation of blood pressure, blood-thinning medicine (such as heparin or warfarin), anti-platelet medicine (such as aspirin or clopidogrel), and rehabilitation therapies. Participants undergoing the Merci Retriever or Penumbra System procedure will have a cerebral arteriogram with pictures taken with dye prior to the procedure to determine the location of the blockage, and following the procedure to determine if blood supply has been restored. The total mechanical embolectomy procedure with either device will take approximately 1 to 2 hours. Participants will have brief neurological exams several times during this time to monitor changes in their neurological condition. Participants will have follow-up visits, including neurological exams, at 30 days and at 90 days. This study is part of the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS), which allows researchers to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients in less than 2 hours, and finding ways to treat additional patients later.

Official Title
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Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy

Conditions
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Stroke

Intervention / Treatment
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* Device: Merci Retriever and Penumbra System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New focal disabling neurologic deficit consistent with acute cerebral ischemia (NIHSS >/= 6) Age >/= 18 ≤ 85 Clot retrieval procedure can be initiated within 8 hours from onset Large vessel proximal anterior circulation occlusion on MR or CT angiography (internal carotid, M1 or M2 MCA) Pretreatment MRI performed according to MR RESCUE protocol Signed informed consent obtained from the patient or patient's legally authorized representative Premorbid modified Rankin score of 0-2 Allowed but not required: patients treated with IV tPA (tissue plasminogen activator) 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: NIHSS >/= 30 Contraindication to MRI (pacemaker etc) Acute intracranial hemorrhage Coma Rapidly improving neurological signs prior to randomization Pre-existing medical, neurological or psychiatric disease that would confound the neurological, functional, or imaging evaluations Pregnancy Known allergy to iodine previously refractory to pretreatment medications Current participation in another experimental treatment protocol Contrast-Enhanced Neck MRA (magnetic resonance angiography) or CTA (computed tomography angiography) suggests proximal ICA occlusion, proximal carotid stenosis > 67%, or dissection INR > 3.0 (international normalized ratio) PTT > 3 x Normal (partial thromboplastin time) Imaging data cannot be processed by the MR RESCUE computer Renal Failure (serum creatinine > 2.0 or Glomerular Filtration Rate [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 sever 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Mechanical Embolectomy<br>Participants will be randomized to receive mechanical embolectomy treatment either with the Merci Retriever or Penumbra System and standard medical care or treatment with standard medical care alone. | Device: Merci Retriever and Penumbra System<br>* The MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Retriever consists of a flexible, nickel titanium (nitinol) wire with a helical-shaped distal tip. The helical distal tip is covered with a platinum radiopaque coil, which facilitates fluoroscopic visualization. The body of the MERCI Retriever is covered with a hydrophilic coating that helps facilitate device placement. The MERCI Retriever is available in 6 configurations (Merci Retrievers X6, L5, L4, L6, V series, DAC). The Penumbra System uses a reperfusion catheter in parallel with a separator component and an aspiration source to achieve separation of the thrombus and subsequent aspiration of the occlusion from the vessel. The system is available in different sizes according to the target vessels (041 Reperfusion Catheter/Separator pair for use in vessels larger than 3mm, notably the ICA and M1; 032 Reperfusion Catheter/Separator pair for use in vessels 2mm - 3mm, notably the M2).<br>|
| No Intervention: 2<br>standard medical care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Modified Rankin Scale Score | Scale name is provided (Modified Rankin Scale) which is a standard measure of functional neurologic outcome in stroke. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. | at 90 days post-stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic Hemorrhagic Transformation | Symptomatic intracranial hemorrhage is defined as 4 point neurologic worsening on the National Institutes of Health Stroke Scale (NIHSS) score associated with parenchymal hematoma type 2 (PH-2*), remote intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage on imaging. The NIHSS is a scale measuring specific neurologic deficits caused by a stroke with scores ranging from 0 to 42, and higher scores indicating more severe neurologic deficits. *from the modified European Cooperative Acute Stroke Study (ECASS) II criteria | from baseline to day 7 | 
| Day 90 Mortality |  | at day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, ischemic stroke, blood clot, Merci Retriever, Penumbra System, embolectomy, magnetic resonance imaging, MRI, CT, SPOTRIAS