Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo "DAWN"

Active, not recruiting

Phase N/A Results N/A

Update History

28 Jul '17
The Summary of Purpose was updated.
New
The purpose of the study is to evaluate the hypothesis that Trevo thrombectomy plus medical management leads to superior clinical outcomes at 90 days as compared to medical management alone in appropriately selected subjects experiencing an acute ischemic stroke when treatment is initiated within 6-24 hours after last seen well.
Old
The purpose of the study is to evaluate the hypothesis that Trevo thrombectomy plus medical management leads to superior clinical outcomes at 90 days as compared to medical management alone in appropriately selected subjects experiencing an acute ischemic stroke when treatment is initiated within 6-24 hours after last seen well.
The description was updated.
New
The study is a prospective, randomized, multi-center, Phase II/III (feasibility/pivotal), adaptive, controlled trial, designed to demonstrate that mechanical thrombectomy using the Trevo Retriever with medical management is superior to medical management alone in improving clinical outcomes at 90 days in appropriately selected wake up and late presenting acute ischemic stroke subjects. The intent of this study is to support the use of the Trevo Retriever beyond the currently labeled 8 hour indicated time limit in wake up, unclear onset, and late presenting ischemic stroke subjects, who currently have no other option besides medical management of their symptoms. Patients with wake-up strokes, strokes with unclear onset time, and witnessed late presenting strokes may potentially benefit from intra-arterial reperfusion therapy. However, an important indicator of whether subjects will benefit or not during this later time window is the confirmation of a large vessel occlusion (LVO), and assessment of the core infarct volume relative to the volume of salvageable penumbra. Therefore, standardized imaging selection of subjects is required for inclusion into the study. This trial has been designed with subject safety in mind, as a seamless Phase II (feasibility) / Phase III (pivotal) adaptive design, in order to address the concerns around potential unknown harms to enrolled subjects. This study will help to answer the question of whether carefully selecting subjects by using Clinical Imaging Mismatch will allow acute ischemic stroke patients who present at or beyond 6 hours from Time Last Seen Well (TLSW) to be considered for intra-arterial intervention. If Trevo thrombectomy plus medical management leads to better clinical outcomes over medical management alone, more patients in the future could receive endovascular treatment (either in addition to or in lieu of IV tPA).
Old
The study is a prospective, randomized, multi-center, Phase II/III (feasibility/pivotal), adaptive, controlled trial, designed to demonstrate that mechanical thrombectomy using the Trevo Retriever with medical management is superior to medical management alone in improving clinical outcomes at 90 days in appropriately selected wake up and late presenting acute ischemic stroke subjects. The intent of this study is to support the use of the Trevo Retriever beyond the currently labeled 8 hour indicated time limit in wake up, unclear onset, and late presenting ischemic stroke subjects, who currently have no other option besides medical management of their symptoms. Patients with wake-up strokes, strokes with unclear onset time, and witnessed late presenting strokes may potentially benefit from intra-arterial reperfusion therapy. However, an important indicator of whether subjects will benefit or not during this later time window is the confirmation of a large vessel occlusion (LVO), and assessment of the core infarct volume relative to the volume of salvageable penumbra. Therefore, standardized imaging selection of subjects is required for inclusion into the study. This trial has been designed with subject safety in mind, as a seamless Phase II (feasibility) / Phase III (pivotal) adaptive design, in order to address the concerns around potential unknown harms to enrolled subjects. This study will help to answer the question of whether carefully selecting subjects by using Clinical Imaging Mismatch will allow acute ischemic stroke patients who present at or beyond 6 hours from Time Last Seen Well (TLSW) to be considered for intra-arterial intervention. If Trevo thrombectomy plus medical management leads to better clinical outcomes over medical management alone, more patients in the future could receive endovascular treatment (either in addition to or in lieu of IV tPA).
The eligibility criteria were updated.
New
General Inclusion Criteria: 1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups: 1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration) 2. Subject is contraindicated for IV t-PA administration 2. Age ≥18 3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume) 4. Subject can be randomized between with 6 to 24 hours after time last known well 5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 6. Anticipated life expectancy of at least 6 months 7. Subject willing/able to return for protocol required follow up visits 8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form* - If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.) Imaging Inclusion Criteria: 1. < 1/3 MCA territory involved, as evidenced by CT or MRI 2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA 3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps: 1. 0-<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 2. 0-<31 cc core infarct and NIHSS ≥ 10 (and age < 80 years old) 3. 31 cc to <51 cc core infarct and NIHSS ≥ 20 (and age < 80 years old) General Exclusion Criteria: 1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history 2. Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel recanalization prior to randomization 3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept) 4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment 5. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) 6. Baseline hemoglobin counts of <7 mmol/L 7. Baseline platelet count < 50,000/uL 8. Abnormal baseline electrolyte parameters as defined by sodium concentration <130 mmol/L, potassium concentration <3 mEq/L or >6 mEq/L 9. Renal failure as defined by a serum creatinine >3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT. 11. Any active or recent hemorrhage within the past 30 days 12. History of severe allergy (more than rash) to contrast medium 13. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled 14. Female who is pregnant or lactating at time of admission 15. Current participation in another investigational drug or device study 16. Presumed septic embolus, or suspicion of bacterial endocarditis 17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization Imaging Exclusion Criteria: 1. Evidence of intracranial hemorrhage on CT/MRI 2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy). 3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment 4. Suspected cerebral vasculitis based on medical history and CTA/MRA 5. Suspected aortic dissection based on medical history and CTA/MRA 6. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device 7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories 8. Significant mass effect with midline shift as confirmed on CT/MRI 9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI
Old
General Inclusion Criteria: 1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups: 1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration) 2. Subject is contraindicated for IV t-PA administration 2. Age ≥18 3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume) 4. Subject can be randomized between with 6 to 24 hours after time last known well 5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 6. Anticipated life expectancy of at least 6 months 7. Subject willing/able to return for protocol required follow up visits 8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form* - If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.) Imaging Inclusion Criteria: 1. < 1/3 MCA territory involved, as evidenced by CT or MRI 2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA 3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps: 1. 0-<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 2. 0-<31 cc core infarct and NIHSS ≥ 10 (and age < 80 years old) 3. 31 cc to <51 cc core infarct and NIHSS ≥ 20 (and age < 80 years old) General Exclusion Criteria: 1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history 2. Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel recanalization prior to randomization 3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept) 4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment 5. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) 6. Baseline hemoglobin counts of <7 mmol/L 7. Baseline platelet count < 50,000/uL 8. Abnormal baseline electrolyte parameters as defined by sodium concentration <130 mmol/L, potassium concentration <3 mEq/L or >6 mEq/L 9. Renal failure as defined by a serum creatinine >3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT. 11. Any active or recent hemorrhage within the past 30 days 12. History of severe allergy (more than rash) to contrast medium 13. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled 14. Female who is pregnant or lactating at time of admission 15. Current participation in another investigational drug or device study 16. Presumed septic embolus, or suspicion of bacterial endocarditis 17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization Imaging Exclusion Criteria: 1. Evidence of intracranial hemorrhage on CT/MRI 2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy). 3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment 4. Suspected cerebral vasculitis based on medical history and CTA/MRA 5. Suspected aortic dissection based on medical history and CTA/MRA 6. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device 7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories 8. Significant mass effect with midline shift as confirmed on CT/MRI 9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI
12 Apr '17
Trial name was updated.
New
Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo
The gender criteria for eligibility was updated to "All."
A location was updated in Los Angeles.
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The overall status was removed for Kaiser Permanente Los Angeles Medical Center.
A location was updated in San Francisco.
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The overall status was removed for California Pacific Medical Center.
A location was updated in Newark.
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The overall status was removed for Christiana Care.
A location was updated in Hollywood.
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The overall status was removed for Memorial Regional.
A location was updated in Jacksonville.
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The overall status was removed for Baptist Jacksonville.
A location was updated in Orlando.
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The overall status was removed for Florida Hospital; Neuroscience Research Center.
A location was updated in Atlanta.
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The overall status was removed for Emory University at Grady Memorial Hospital.
A location was updated in Chicago.
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The overall status was removed for Rush University Medical Center.
A location was updated in Kansas City.
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The overall status was removed for University of Kansas Medical Center.
A location was updated in Pontiac.
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The overall status was removed for St. Joseph Mercy - Oakland.
A location was updated in Trenton.
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The overall status was removed for Capital Health System.
A location was updated in Buffalo.
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The overall status was removed for Buffalo General Medical Center.
A location was updated in Cleveland.
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The overall status was removed for University Hospitals Case Medical Center.
A location was updated in Columbus.
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The overall status was removed for Riverside Methodist Hospital/ Ohio Health Research Institute.
A location was updated in Abington.
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The overall status was removed for Abington Memorial Hospital.
A location was updated in Pittsburgh.
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The overall status was removed for UPMC Stroke Institute.
A location was updated in Chattanooga.
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The overall status was removed for Erlanger Health System.
A location was updated in Harlingen.
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The overall status was removed for Valley Baptist Medical Center-Harlingen.
A location was updated in Plano.
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The overall status was removed for North Texas Stroke Center HCA (dba TSI).
A location was updated in Parkville.
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The overall status was removed for Royal Melbourne.
A location was updated in Montpellier.
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The overall status was removed for Hôpital Gui de Chauliac.
A location was updated in Toulouse.
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The overall status was removed for Hopital Purpan - Toulouse.
9 Feb '16
The eligibility criteria were updated.
New
General Inclusion Criteria: 1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups: 1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration) 2. Subject is contraindicated for IV t-PA administration 2. Age ≥18 3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume) 4. Subject can be randomized between with 6 to 24 hours after time last known well 5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 6. Anticipated life expectancy of at least 6 months 7. Subject willing/able to return for protocol required follow up visits 8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form* - If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.) Imaging Inclusion Criteria: 1. < 1/3 MCA territory involved, as evidenced by CT or MRI 2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA 3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps: 1. 0-<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 2. 0-<31 cc core infarct and NIHSS ≥ 10 (and age < 80 years old) 3. 31 cc to <51 cc core infarct and NIHSS ≥ 20 (and age < 80 years old) General Exclusion Criteria: 1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history 2. Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel recanalization prior to randomization 3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept) 4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment 5. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) 6. Baseline hemoglobin counts of <7 mmol/L 7. Baseline platelet count < 50,000/uL 8. Abnormal baseline electrolyte parameters as defined by sodium concentration <130 mmol/L, potassium concentration <3 mEq/L or >6 mEq/L 9. Renal failure as defined by a serum creatinine >3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT. 11. Any active or recent hemorrhage within the past 30 days 12. History of severe allergy (more than rash) to contrast medium 13. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled 14. Female who is pregnant or lactating at time of admission 15. Current participation in another investigational drug or device study 16. Presumed septic embolus, or suspicion of bacterial endocarditis 17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization Imaging Exclusion Criteria: 1. Evidence of intracranial hemorrhage on CT/MRI 2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy). 3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment 4. Suspected cerebral vasculitis based on medical history and CTA/MRA 5. Suspected aortic dissection based on medical history and CTA/MRA 6. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device 7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories 8. Significant mass effect with midline shift as confirmed on CT/MRI 9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI
Old
General Inclusion Criteria: 1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups: 1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration) 2. Subject is contraindicated for IV t-PA administration 2. Age ≥18 3. Baseline NIHSS ≥10 (assessed within one hour prior to measuring core infarct volume) 4. Subject can be randomized between with 6 to 24 hours after time last known well 5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 6. Anticipated life expectancy of at least 6 months 7. Subject willing/able to return for protocol required follow up visits 8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form* Imaging Inclusion Criteria: 1. < 1/3 MCA territory involved, as evidenced by CT or MRI 2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA 3. Clinical Imaging Mismatch (CIM) defined as one of the following on RAPID MR-DWI or CTP-rCBF maps: 1. 0-20 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 2. 0-30 cc core infarct and NIHSS ≥ 10 (and age < 80 years old) 3. 31 cc to < 50 cc core infarct and NIHSS ≥ 20 (and age < 80 years old) General Exclusion Criteria: 1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history 2. Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel recanalization prior to randomization 3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept) 4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment 5. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) 6. Renal failure as defined by a serum creatinine >3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 7. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal; If factor Xa inhibitor (e.g. apixaban) < 24 hrs ago must have normal ecarin clotting time and if 24-48 hrs ago must have normal PTT. 8. Any active or recent hemorrhage within the past 30 days 9. Baseline platelet count < 50,000/uL 10. History of severe allergy (more than rash) to contrast medium 11. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled 12. Female who is pregnant or lactating at time of admission 13. Current participation in another investigational drug or device study or registry 14. Presumed septic embolus, or suspicion of bacterial endocarditis 15. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization Imaging Exclusion Criteria: 1. Evidence of intracranial hemorrhage on CT/MRI 2. Evidence of internal carotid artery flow limiting dissection on CTA/MRA 3. Severe proximal extra-cranial carotid artery stenosis, or occlusion of any etiology, where concurrent vessel angioplasty or stenting is expected to be necessary and the procedure cannot be delayed until after the 24 (-6/+24) hours assessments have been completed 4. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment 5. Suspected cerebral vasculitis based on medical history and CTA/MRA 6. Suspected aortic dissection based on medical history and CTA/MRA 7. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device 8. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories 9. Significant mass effect with midline shift as confirmed on CT/MRI 10. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI
7 Feb '15
A location was updated in Pontiac.
New
The overall status was removed for St. Joseph Mercy - Oakland.