Interventional Management of Stroke (IMS) III Trial "IMSIII"

Terminated

Phase 3 Results

Update History

11 Feb '14
The Summary of Purpose was updated.
New
The purpose of this study is to compare two different treatment approaches to recanalization started within 3 hours of symptom onset—combined intravenous (IV) and endovascular therapy and standard intravenous (IV) rt-PA alone.
Old
The purpose of this study is to compare two different treatment approaches—combined intravenous and intra-arterial treatment including recombinant tissue plasminogen activator (rt-PA) and standard intravenous (IV) rt-PA—to restoring blood flow to the brain.
The description was updated.
New
Stroke remains a major cause of death and disability. Acute thrombolytic therapy offers the potential to achieve early recanalization (reopening of blocked arteries), save tissues, and improve outcome. Currently, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy. IV rt-PA is an effective therapy for acute ischemic stroke but has substantial limitations when used alone to open blocked arteries The Interventional Management of Stroke (IMS III) Trial is a multi-center study that will compare two different treatment approaches for restoring blood flow to the brain. One approach, giving the clot-dissolving drug rt-PA, is already FDA-approved when given through a vein (IV). This treatment will be compared to a new approach, giving rt-PA at a lower dose first through IV in the arm and then, if a blood clot in the brain artery is found, through a small tube or catheter at the site of the blood clot (intra-arterial or IA) to see which is better. Both approaches must be initiated within three hours of stroke onset. The primary goal of this trial is to determine if individuals with ischemic stroke treated with rt-PA using an endovascular therapy approach to recanalization started within 3 hours of onset are more likely to have a better outcome than individuals treated with standard IV rt-PA alone. While information on device use was collected, individual device performance was not a primary outcome. Nine hundred participants with moderate to severe ischemic stroke will be enrolled at more than 50 centers in the United States, Canada, Australia and Europe. Subjects will be randomized in a 2:1 ratio to receive endovascular therapy or IV only with adjustment for clinical site and NIHSSS strata. If enrolled under Amendment 5 or later both treatment groups will receive the standard approved therapy dose of rt-PA (0.9 mg/kg, 90 mg max) administered intravenously over one hour. The consent process and randomization can take place prior to or anytime up to forty minutes after the IV bolus dose. If, at the 40 minute time point, no consent has been obtained or randomization has not been completed, the patient will no longer be eligible for IMS III enrollment. After consent, the endovascular therapy group will then undergo immediate angiography. If clot is not demonstrated, no more treatment is administered. If clot is demonstrated, the neurointerventionalist will then choose from currently available but trial defined endovascular therapy approaches, choosing the treatment they feel will be most effective in attempting to reopen the blocked artery. These approaches utilize local regulatory, US FDA and IMS III Executive Committee approved devices for the intra-arterial infusion of investigational rt-PA using standard microcatheter or the EKOS Micro-Infusion Catheter® (in US) or embolectomy devices including the Concentric Retriever Device®, the Penumbra System ™, or the Solitaire™ FR Revascularization Device. All devices must be used per the manufacturer's instructions for use. Endovascular therapy, whether initially with the Merci® Retriever, EKOS Micro-Infusion Catheter, Penumbra System™, Solitaire™, a future device, or infusion of IA rt-PA via a standard microcatheter, must be started within 5 hours and completed within 7 hours of symptom onset. The maximum dose of IA rt-PA is 22mg (maximum 2 to 4 mg bolus and infusion at a rate of 10 mg/hr). Use of tandem devices (i.e. EKOS Micro-Infusion Catheter, Merci Retriever®, Penumbra System™, or Solitaire™) in a single case is a protocol violation. Only standard microcatheter rt-PA infusion therapy may be administered following attempt with a device. The primary measure of benefit in this trial is the ability of the individual with stroke to live and function independently 3 months after the stroke. This trial will also determine and compare the safety and cost effectiveness of the combined endovascular therapy to the standard IV rt-PA approach. Duration of the study for participants is approximately 12 months.
Old
Stroke remains a major cause of death and disability. Acute thrombolytic therapy offers the potential to achieve early recanalization (reopening of blocked arteries), save tissues, and improve outcome. Currently, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy. IV rt-PA is an effective therapy for acute ischemic stroke but has substantial limitations when used alone to open blocked arteries The Interventional Management of Stroke (IMS III) Trial is a multi-center study that will compare two different treatment approaches for restoring blood flow to the brain. One approach, giving the clot-dissolving drug rt-PA, is already FDA-approved when given through a vein (IV). This treatment will be compared to a new approach, giving rt-PA at a lower dose first through IV in the arm and then, if a blood clot in the brain artery is found, through a small tube or catheter at the site of the blood clot (intra-arterial or IA) to see which is better. Both approaches must be initiated within three hours of stroke onset. The primary goal of this trial is to determine if individuals with ischemic stroke treated with rt-PA using a combined IV/IA approach to recanalization started within 3 hours of onset are more likely to have a better outcome than individuals treated with standard IV rt-PA alone. Nine hundred participants with moderate to severe ischemic stroke will be enrolled at more than 50 centers in the United States, Canada, Australia and Europe. Subjects will be randomized in a 2:1 ratio with more subjects enrolled in the combined IV/IA group. If enrolled under Amendment 5 or later both treatment groups will receive the standard approved therapy dose of rt-PA (0.9 mg/kg, 90 mg max) administered intravenously over one hour. The consent process and randomization can take place prior to or anytime up to forty minutes after the IV bolus dose. If, at the 40 minute time point, no consent has been obtained or randomization has not been completed, the patient will no longer be eligible for IMS III enrollment. After consent, the combined IV/IA group will then undergo immediate angiography. If clot is not demonstrated, no more treatment is administered. If clot is demonstrated, the neurointerventionalist will then choose from currently available but trial defined intra-arterial treatment approaches, choosing the treatment they feel will be most effective in attempting to reopen the blocked artery. These approaches utilize local regulatory, US FDA and IMS III Executive Committee approved devices for the intra-arterial infusion of investigational rt-PA using standard microcatheter or the EKOS Micro-Infusion Catheter® (in US) or embolectomy devices including the Concentric Retriever Device®, the Penumbra System ™, or the Solitaire™ FR Revascularization Device. All devices must be used per the manufacturer's instructions for use. Intra-arterial therapy, whether initially with the Merci® Retriever, EKOS Micro-Infusion Catheter, Penumbra System™, Solitaire™, a future device, or infusion of IA rt-PA via a standard microcatheter, must be started within 5 hours and completed within 7 hours of symptom onset. The maximum dose of IA rt-PA is 22mg (maximum 2 to 4 mg bolus and infusion at a rate of 10 mg/hr). Use of tandem devices (i.e. EKOS Micro-Infusion Catheter, Merci Retriever®, Penumbra System™, or Solitaire™) in a single case is a protocol violation. Only standard microcatheter rt-PA infusion therapy may be administered following attempt with a device. The primary measure of benefit in this trial is the ability of the individual with stroke to live and function independently 3 months after the stroke. This trial will also determine and compare the safety and cost effectiveness of the combined IV/IA approach to the standard IV rt-PA approach. Duration of the study for participants is approximately 12 months.
18 Jan '13
The eligibility criteria were updated.
New
Inclusion Criteria - Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not had their 83rd birthday) - Initiation of intravenous rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the subject was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep) - An NIHSSS >/= 10 at the time that intravenous rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients. - Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization Exclusion Criteria - History of stroke in the past 3 months - Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation - Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal - Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg) or aggressive measures to lower BP to below these limits are needed. - Presumed septic embolus, or suspicion of bacterial endocarditis - Presumed pericarditis, including pericarditis after acute MI - Suspicion of aortic dissection - Recent (within 30 days) surgery or biopsy of parenchymal organ - Recent (within 30 days) trauma, with internal injuries or ulcerative wounds - Recent (within 90 days) severe head trauma or head trauma with loss of consciousness - Any active or recent (within 30 days) hemorrhage - Pts with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency or oral anticoagulant therapy require coagulation labs results prior to enrollment. Any subject with INR > 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment. - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission - Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25 - Requires hemodialysis or peritoneal dialysis, or has a contraindication to an angiogram for whatever reason - Received heparin or a direct thrombin inhibitor (Angiomax, argatroban, Refludan, Pradaxa) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible - History of an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days - History of seizure at onset of stroke - History of a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be < 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) - Other serious, advanced, or terminal illness - Any other condition that the investigator feels would pose a significant hazard to the subject if Activase (Alteplase) therapy is initiated - Current participation in another research drug treatment protocol - Informed consent is not or cannot be obtained. - High density lesion consistent with hemorrhage of any degree on baseline imaging - Significant mass effect with midline shift on baseline imaging - Large (>1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. (ASPECTS of < 4 can be used as a guideline) Sulcal effacement and/or loss of grey-white differentiation are not contraindications to tx - CT evidence of intrapararenchymal tumor - Baseline CTA without evidence of arterial occlusion
Old
Clinical Inclusion Criteria - Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not had their 83rd birthday) - Initiation of intravenous rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the subject was witnessed to be at baseline - An NIHSSS >/= 10 at the time that intravenous rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients - Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization Clinical Exclusion Criteria - History of stroke in the past 3 months - Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation - Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal - Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg or aggressive measures to lower BP to below these limits are needed - Presumed septic embolus, or suspicion of bacterial endocarditis - Presumed pericarditis, including pericarditis after acute MI - Suspicion of aortic dissection - Recent (within 30 days) surgery or biopsy of parenchymal organ - Recent (within 30 days) trauma, with internal injuries or ulcerative wounds - Recent (within 90 days) severe head trauma or head trauma with loss of consciousness - Any active or recent (within 30 days) hemorrhage - Pts with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency or oral anticoagulant therapy require coagulation labs results prior to enrollment. Any subject with INR > 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission. - Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25 - Subject who require hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason - Subjects who have received heparin or a direct thrombin inhibitor (Angiomax™,argatroban,Refludan™, Pradaxa™) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible - Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days - Subjects with a seizure at onset of stroke - Subjects with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be < 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) - Other serious, advanced, or terminal illness - Any other condition that the investigator feels would pose a significant hazard to the subject if Activase®/Actilyse®(Alteplase) therapy is initiated - Current participation in another research drug treatment protocol - Written Informed consent is not or cannot be obtained per regional regulatory and or legal requirements CT Scan Exclusion Criteria - High density lesion consistent with hemorrhage of any degree - Significant mass effect with midline shift - Large (>1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. (ASPECTS of < 4 can be used as a guideline) Sulcal effacement and/or loss of grey-white differentiation are not contraindications to tx - CT evidence of intrapararenchymal tumor - Baseline CTA without evidence of an arterial occlusion (NOTE: The trial does not require baseline CTA imaging, if CTA is routinely performed prior to IV rt-PA lesion information obtained should be used to satisfy this exclusion)
1 May '12
A location was updated in Birmingham.
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The overall status was removed for University of Alabama Birmingham.
A location was updated in Phoenix.
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The overall status was removed for Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center, 222 W. Thomas Road, Suite 404.
A location was updated in Scottsdale.
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The overall status was removed for Mayo Clinic Arizona, 5777 E. Mayo Blvd..
A location was updated in Los Angeles.
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The overall status was removed for UCLA Medical Center, 924 Westwood Blvd., Suite 300.
A location was updated in Newport Beach.
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The overall status was removed for Hoag Memorial Hospital.
A location was updated in Santa Monica.
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The overall status was removed for Santa Monica-UCLA Medical Center, 1250 16th Street.
A location was updated in Englewood.
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The overall status was removed for Colorado Neurological Institute, Swedish Medical Center, 501 E. Hampden Ave..
A location was updated in Hartford.
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The overall status was removed for Stroke Center at Hartford, 80 Seymour St. Rm JB603.
A location was updated in Clearwater.
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The overall status was removed for Morton Plant Mease Health Care, 300 Pinellas Street MS 49.
A location was updated in Miami.
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The overall status was removed for University of Miami Miller School of Medicine.
A location was updated in Sarasota.
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The overall status was removed for Intercoastal Medical Group.
A location was updated in Elk Grove Village.
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The overall status was removed for Alexian Brothers Medical Center, 800 Biesterfield Rd..
A location was updated in Des Moines.
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The overall status was removed for Ruan Neurological Mercy Medical Center, 1111 6th Ave., Ste. 400.
A location was updated in Edgewood.
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The overall status was removed for St. Elizabeth Medical Center South, One Medical Village Drive.
A location was updated in Florence.
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The overall status was removed for St Luke's West Hospital, 7380 Turfway Rd..
A location was updated in Ft. Thomas.
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The overall status was removed for St. Luke's Hospital East, 85 N. Grand Ave..
A location was updated in Louisville.
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The overall status was removed for University of Louisville, Kentucky Neuroscience Research, Stroke Research, 401 East Chestnut Street, Suite 520.
A location was updated in Baltimore.
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The overall status was removed for Johns Hopkins University, 1500 Orleans St. 3M South.
A location was updated in Boston.
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The overall status was removed for Massachusetts General Hospital, 55 Fruit Street.
A location was updated in Burlington.
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The overall status was removed for Lahey Clinic Medical Center.
A location was updated in Detroit.
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The overall status was removed for Henry Ford Hospital, 2799 W Grand Blvd, CFP-260.
A location was updated in East Lansing.
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The overall status was removed for Michigan State University, Sparrow Hospital, B 401 Clinical Center.
A location was updated in Jackson.
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The overall status was removed for University Of Mississippi Medical Center.
A location was updated in St. Louis.
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The overall status was removed for Washington University/Barnes Jewish Hospital, 660 S. Euclid Avenue.
A location was updated in St. Louis.
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The overall status was removed for St. Louis University.
A location was updated in Rochester.
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The overall status was removed for University of Rochester Medical Center.
A location was updated in Syracuse.
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The overall status was removed for SUNY Upstate Medical University.
A location was updated in Asheville.
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The overall status was removed for Mission Hospital, 509 Biltmore Avenue.
A location was updated in Chapel Hill.
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The overall status was removed for University of North Carolina, CB # 7025, 7003 Neurosciences Hospital, 7th Floor.
A location was updated in Cincinnati.
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The overall status was removed for Good Samaritan Hospital, 375 Dixmyth Ave..
A location was updated in Cincinnati.
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The overall status was removed for The University Hospital, 234 Goodman Ave..
A location was updated in Cincinnati.
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The overall status was removed for The Jewish Hospital of Cincinnati, 4777 East Galbraith Rd.
A location was updated in Cincinnati.
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The overall status was removed for Mercy Hospital Anderson, 7500 State Rd.
A location was updated in Cincinnati.
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The overall status was removed for The Christ Hospital, 2139 Auburn Ave..
A location was updated in Cincinnati.
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The overall status was removed for Mercy Hospital, Mt Airy, 2446 Kipling Ave..
A location was updated in Cincinnati.
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The overall status was removed for Mercy Hospital, Western Hills, 3131 Queen City Ave..
A location was updated in Cleveland.
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The overall status was removed for University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508.
A location was updated in Columbus.
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The overall status was removed for Riverside Methodist Hospital, 3535 Olentangy River Road.
A location was updated in Fairfield.
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The overall status was removed for Mercy Hospital Fairfield, 3000 Mack Rd..
A location was updated in Montgomery.
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The overall status was removed for Bethesda North Hospital, 10500 Montgomery Rd..
A location was updated in Portland.
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The overall status was removed for OHSU, Oregon Stroke Center, Providence St. Vincent's Hospital, Providence Portland Hospital.
A location was updated in Abington.
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The overall status was removed for Abington Memorial Hospital.
A location was updated in Allentown.
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The overall status was removed for Lehigh Valley Hospital Center, 1200 South Cedar Crest Blvd..
A location was updated in Hershey.
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The overall status was removed for PENN State M.S. Hershey Medical Center, 500 University Drive MC: HS 86, Long Lane Rom HG:212.
A location was updated in Pittsburgh.
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The overall status was removed for Allegheny General Hospital, 420 East North Avenue, East Wing Office Bldg., Suite 206.
A location was updated in Pittsburgh.
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The overall status was removed for University of Pittsburgh, Medical Center, 200 Lothrop Street, PUH C-400.
A location was updated in Charleston.
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The overall status was removed for Medical University of South Carolina.
A location was updated in Austin.
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The overall status was removed for University Medical Center at Brackenridge Hospital.
A location was updated in Houston.
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The overall status was removed for University of Texas Medical School at Houston, 6431 Fannin, MSB 7.044.
A location was updated in Charlottesville.
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The overall status was removed for University of Virginia Health System.
A location was updated in Milwaukee.
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The overall status was removed for Froedtert Hospital, Medical College of Wisconsin, 9200 W. Wisconsin Avenue.
A location was updated in Camperdown.
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The overall status was removed for Royal Prince Alfred Hospital, Level 10 King George V Building, Missenden Rd.
A location was updated in Sydney.
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The overall status was removed for St. Vincent's Hospital, Clincial Trial Centre Level 5, 378 Victoria St., Darlinghurst.
A location was updated in Victoria.
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The overall status was removed for Royal Melbourne Hospital, Dept. of Neurology, 4 East, Grattan St, Parkville.
A location was updated in Victoria.
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The overall status was removed for Monash Medical Center, Dept. of Neurology, 246 Clayton Rd, Clayton.
A location was updated in Calgary.
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The overall status was removed for University of Calgary, Calgary Health Region/Foothills Hospital, 1403 29th Street NW.
A location was updated in Vancouver.
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The overall status was removed for University of British Columbia, Vancouver General Hospital, VGH Stroke Program, Gordon & Leslie Diamond Healthcare Centre, 2775 Laurel St., 8th Fl., Ste. 8295.
A location was updated in Ottawa.
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The overall status was removed for The Ottawa Hospital, Civic Campus, CPC Main, RM 36, Box 608, 1053 Carling Avenue.
A location was updated in Toronto.
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The overall status was removed for Toronto Western Hospital, 5th Floor Rm. 447, 399 Bathurst St..
A location was updated in Toronto.
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The overall status was removed for Sunnybrook Health Sciences Centre.
A location was updated in Toronto.
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The overall status was removed for St. Michael's Hospital.
A location was updated in Montreal.
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The overall status was removed for Centre Hospital University of Montreal.
A location was updated in Paris.
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The overall status was removed for Bichat Stroke Centre.
A location was updated in Dresden.
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The overall status was removed for Technische Universität, Dresden.
A location was updated in Freiburg.
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The overall status was removed for University of Freiburg.
A location was updated in Greifswald.
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The overall status was removed for Ernst Moritz Arndt University.
A location was updated in Halle.
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The overall status was removed for Martin-Luther University.
A location was updated in Hamburg.
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The overall status was removed for Asklepios Klinik Nord Heidberg.
A location was updated in Nieuwegein.
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The overall status was removed for St. Antonius Hospital.
A location was updated in Badalona.
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The overall status was removed for Hospital Universitari Germans Trias i Pujol.
A location was updated in Barcelona.
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The overall status was removed for Hospital Vall d´Hebron.
A location was updated in Basel.
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The overall status was removed for University Hospital Basel.
A location was updated in Lausanne.
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The overall status was removed for Centre Hospitalier, University Vaudois.
9 Feb '12
The description was updated.
New
Stroke remains a major cause of death and disability. Acute thrombolytic therapy offers the potential to achieve early recanalization (reopening of blocked arteries), save tissues, and improve outcome. Currently, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy. IV rt-PA is an effective therapy for acute ischemic stroke but has substantial limitations when used alone to open blocked arteries The Interventional Management of Stroke (IMS III) Trial is a multi-center study that will compare two different treatment approaches for restoring blood flow to the brain. One approach, giving the clot-dissolving drug rt-PA, is already FDA-approved when given through a vein (IV). This treatment will be compared to a new approach, giving rt-PA at a lower dose first through IV in the arm and then, if a blood clot in the brain artery is found, through a small tube or catheter at the site of the blood clot (intra-arterial or IA) to see which is better. Both approaches must be initiated within three hours of stroke onset. The primary goal of this trial is to determine if individuals with ischemic stroke treated with rt-PA using a combined IV/IA approach to recanalization started within 3 hours of onset are more likely to have a better outcome than individuals treated with standard IV rt-PA alone. Nine hundred participants with moderate to severe ischemic stroke will be enrolled at more than 50 centers in the United States, Canada, Australia and Europe. Subjects will be randomized in a 2:1 ratio with more subjects enrolled in the combined IV/IA group. If enrolled under Amendment 5 or later both treatment groups will receive the standard approved therapy dose of rt-PA (0.9 mg/kg, 90 mg max) administered intravenously over one hour. The consent process and randomization can take place prior to or anytime up to forty minutes after the IV bolus dose. If, at the 40 minute time point, no consent has been obtained or randomization has not been completed, the patient will no longer be eligible for IMS III enrollment. After consent, the combined IV/IA group will then undergo immediate angiography. If clot is not demonstrated, no more treatment is administered. If clot is demonstrated, the neurointerventionalist will then choose from currently available but trial defined intra-arterial treatment approaches, choosing the treatment they feel will be most effective in attempting to reopen the blocked artery. These approaches utilize local regulatory, US FDA and IMS III Executive Committee approved devices for the intra-arterial infusion of investigational rt-PA using standard microcatheter or the EKOS Micro-Infusion Catheter® (in US) or embolectomy devices including the Concentric Retriever Device®, the Penumbra System ™, or the Solitaire™ FR Revascularization Device. All devices must be used per the manufacturer's instructions for use. Intra-arterial therapy, whether initially with the Merci® Retriever, EKOS Micro-Infusion Catheter, Penumbra System™, Solitaire™, a future device, or infusion of IA rt-PA via a standard microcatheter, must be started within 5 hours and completed within 7 hours of symptom onset. The maximum dose of IA rt-PA is 22mg (maximum 2 to 4 mg bolus and infusion at a rate of 10 mg/hr). Use of tandem devices (i.e. EKOS Micro-Infusion Catheter, Merci Retriever®, Penumbra System™, or Solitaire™) in a single case is a protocol violation. Only standard microcatheter rt-PA infusion therapy may be administered following attempt with a device. The primary measure of benefit in this trial is the ability of the individual with stroke to live and function independently 3 months after the stroke. This trial will also determine and compare the safety and cost effectiveness of the combined IV/IA approach to the standard IV rt-PA approach. Duration of the study for participants is approximately 12 months.
Old
Stroke remains a major cause of death and disability. Acute thrombolytic therapy offers the potential to achieve early recanalization (reopening of blocked arteries), save tissues, and improve outcome. Currently, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy. IV rt-PA is an effective therapy for acute ischemic stroke but has substantial limitations when used alone to open blocked arteries The Interventional Management of Stroke (IMS III) Trial is a multi-center study that will compare two different treatment approaches for restoring blood flow to the brain. One approach, giving the clot-dissolving drug rt-PA, is already FDA-approved when given through a vein (IV). This treatment will be compared to a new approach, giving rt-PA at a lower dose first through IV in the arm and then, if a blood clot in the brain artery is found, through a small tube or catheter at the site of the blood clot (intra-arterial or IA) to see which is better. Both approaches must be initiated within three hours of stroke onset. The primary goal of this trial is to determine if individuals with ischemic stroke treated with rt-PA using a combined IV/IA approach to recanalization started within 3 hours of onset are more likely to have a better outcome than individuals treated with standard IV rt-PA alone. Nine hundred participants with moderate to severe ischemic stroke will be enrolled at more than 50 centers in the United States, Canada, and Australia. Participants will be assigned randomly to one of 2 groups. Two participants will be randomized to the combined approach for every one participant randomized to standard IV rt-PA. Group one will receive the standard dose of IV rt-PA given over an hour. Group two will receive the standard dose of IV rt-PA for only 40 minutes and then undergo an angiogram test (cerebral angiography) right after the medicine is given to check for blood clots. If a clot is not seen then no more treatment will be given. If a clot is seen, the doctor (a neurointerventionalist) will then choose, based on the location and extent of the blood clot, one of 4 possible IA treatments given directly in the brain artery that will be most effective in reopening the blocked artery. All of the IA treatments used—embolectomy therapy with either the Merci® Retriever or The Penumbra System™, or rt-PA infusion through the EKOS® Micro-Infusion Catheter, concurrent with delivery of low-intensity ultrasound energy, or infusion of rt-PA though a standard microcatheter at the site of the blood clot in the brain artery. The primary measure of benefit in this trial is the ability of the individual with stroke to live and function independently 3 months after the stroke. This trial will also determine and compare the safety and cost effectiveness of the combined IV/IA approach to the standard IV rt-PA approach. Duration of the study for participants is approximately 12 months.
The eligibility criteria were updated.
New
Clinical Inclusion Criteria - Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not had their 83rd birthday) - Initiation of intravenous rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the subject was witnessed to be at baseline - An NIHSSS >/= 10 at the time that intravenous rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients - Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization Clinical Exclusion Criteria - History of stroke in the past 3 months - Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation - Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal - Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg or aggressive measures to lower BP to below these limits are needed - Presumed septic embolus, or suspicion of bacterial endocarditis - Presumed pericarditis, including pericarditis after acute MI - Suspicion of aortic dissection - Recent (within 30 days) surgery or biopsy of parenchymal organ - Recent (within 30 days) trauma, with internal injuries or ulcerative wounds - Recent (within 90 days) severe head trauma or head trauma with loss of consciousness - Any active or recent (within 30 days) hemorrhage - Pts with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency or oral anticoagulant therapy require coagulation labs results prior to enrollment. Any subject with INR > 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission. - Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25 - Subject who require hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason - Subjects who have received heparin or a direct thrombin inhibitor (Angiomax™,argatroban,Refludan™, Pradaxa™) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible - Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days - Subjects with a seizure at onset of stroke - Subjects with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be < 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) - Other serious, advanced, or terminal illness - Any other condition that the investigator feels would pose a significant hazard to the subject if Activase®/Actilyse®(Alteplase) therapy is initiated - Current participation in another research drug treatment protocol - Written Informed consent is not or cannot be obtained per regional regulatory and or legal requirements CT Scan Exclusion Criteria - High density lesion consistent with hemorrhage of any degree - Significant mass effect with midline shift - Large (>1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. (ASPECTS of < 4 can be used as a guideline) Sulcal effacement and/or loss of grey-white differentiation are not contraindications to tx - CT evidence of intrapararenchymal tumor - Baseline CTA without evidence of an arterial occlusion (NOTE: The trial does not require baseline CTA imaging, if CTA is routinely performed prior to IV rt-PA lesion information obtained should be used to satisfy this exclusion)
Old
Inclusion Criteria: - Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not their 83rd birthday). - Initiation of IV rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep). - An NIHSSS ≥ 10 at the time that IV rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients. - Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization Exclusion Criteria: - History of stroke in the past 3 months. - Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation. - Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal. - Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg; or aggressive measures to lower blood pressure to below these limits are needed. - Presumed septic embolus, or suspicion of bacterial endocarditis - Presumed pericarditis including pericarditis after acute myocardial infarction. - Suspicion of aortic dissection - Recent (within 30 days) surgery or biopsy of parenchymal organ. - Recent (within 30 days) trauma, with internal injuries or ulcerative wounds. - Recent (within 90 days) severe head trauma or head trauma with loss of consciousness. - Any active or recent (within 30 days) hemorrhage. - Patients with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy require coagulation lab results prior to enrollment. Any subject with INR greater than 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment. - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission. - Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25 - Patients that require hemodialysis or peritoneal dialysis, or who have a contradiction to an angiogram for whatever reason . - Patients who have received heparin or a direct thrombin inhibitor (Angiomax™ or argatroban, Refludan™) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible. - Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days. - Patients with a seizure at onset of stroke - Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be < 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) - Other serious, advanced, or terminal illness. - Any other condition that the investigator feels would pose a significant hazard to the patient if Activase (Alteplase) therapy is initiated. - Current participation in another research drug treatment protocol. - Informed consent is not or cannot be obtained. For example, obtunded patients are not automatically excluded from the study. However, if the next of kin or legal guardian (i.e., the individual legally empowered in the state where the consent is obtained) cannot provide consent, randomization and entry into the study could not proceed. IMAGING Exclusion Criteria: - High density lesion consistent with hemorrhage of any degree. - Significant mass effect with midline shift. - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging. An ASPECTS of < 4can be used as a guideline when evaluating >1/3 region of territory involvement. Sulcal effacement and / or loss of grey-white differentiation alone are not contraindications for treatment.
A location was updated in Phoenix.
New
The overall status was removed for Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center, 222 W. Thomas Road, Suite 404.
A location was updated in Hartford.
New
The overall status was removed for Stroke Center at Hartford, 80 Seymour St. Rm JB603.
A location was updated in Baltimore.
New
The overall status was removed for Johns Hopkins University, 1500 Orleans St. 3M South.
A location was updated in Boston.
New
The overall status was removed for Massachusetts General Hospital, 55 Fruit Street.
A location was updated in East Lansing.
New
The overall status was removed for Michigan State University, Sparrow Hospital, B 401 Clinical Center.
A location was updated in Cleveland.
New
The overall status was removed for University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508.
A location was updated in Austin.
New
The overall status was removed for University Medical Center at Brackenridge Hospital.
A location was updated in Houston.
New
The overall status was removed for University of Texas Medical School at Houston, 6431 Fannin, MSB 7.044.
6 Oct '11
The eligibility criteria were updated.
New
Inclusion Criteria: - Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not their 83rd birthday). - Initiation of IV rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep). - An NIHSSS ≥ 10 at the time that IV rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients. - Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization Exclusion Criteria: - History of stroke in the past 3 months. - Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation. - Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal. - Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg; or aggressive measures to lower blood pressure to below these limits are needed. - Presumed septic embolus, or suspicion of bacterial endocarditis - Presumed pericarditis including pericarditis after acute myocardial infarction. - Suspicion of aortic dissection - Recent (within 30 days) surgery or biopsy of parenchymal organ. - Recent (within 30 days) trauma, with internal injuries or ulcerative wounds. - Recent (within 90 days) severe head trauma or head trauma with loss of consciousness. - Any active or recent (within 30 days) hemorrhage. - Patients with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy require coagulation lab results prior to enrollment. Any subject with INR greater than 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment. - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission. - Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25 - Patients that require hemodialysis or peritoneal dialysis, or who have a contradiction to an angiogram for whatever reason . - Patients who have received heparin or a direct thrombin inhibitor (Angiomax™ or argatroban, Refludan™) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible. - Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days. - Patients with a seizure at onset of stroke - Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be < 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) - Other serious, advanced, or terminal illness. - Any other condition that the investigator feels would pose a significant hazard to the patient if Activase (Alteplase) therapy is initiated. - Current participation in another research drug treatment protocol. - Informed consent is not or cannot be obtained. For example, obtunded patients are not automatically excluded from the study. However, if the next of kin or legal guardian (i.e., the individual legally empowered in the state where the consent is obtained) cannot provide consent, randomization and entry into the study could not proceed. IMAGING Exclusion Criteria: - High density lesion consistent with hemorrhage of any degree. - Significant mass effect with midline shift. - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging. An ASPECTS of < 4can be used as a guideline when evaluating >1/3 region of territory involvement. Sulcal effacement and / or loss of grey-white differentiation alone are not contraindications for treatment.
Old
Inclusion Criteria: - Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not their 83rd birthday). - Initiation of IV rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep). - An NIHSSS ? 10 at the time that IV rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients. - Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization Exclusion Criteria: - History of stroke in the past 3 months. - Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation. - Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal. - Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg; or aggressive measures to lower blood pressure to below these limits are needed. - Presumed septic embolus, or suspicion of bacterial endocarditis - Presumed pericarditis including pericarditis after acute myocardial infarction. - Suspicion of aortic dissection - Recent (within 30 days) surgery or biopsy of parenchymal organ. - Recent (within 30 days) trauma, with internal injuries or ulcerative wounds. - Recent (within 90 days) severe head trauma or head trauma with loss of consciousness. - Any active or recent (within 30 days) hemorrhage. - Patients with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy require coagulation lab results prior to enrollment. Any subject with INR greater than 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment. - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission. - Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25 - Patients that require hemodialysis or peritoneal dialysis, or who have a contradiction to an angiogram for whatever reason . - Patients who have received heparin or a direct thrombin inhibitor (Angiomax™ or argatroban, Refludan™) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible. - Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days. - Patients with a seizure at onset of stroke - Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be < 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) - Other serious, advanced, or terminal illness. - Any other condition that the investigator feels would pose a significant hazard to the patient if Activase (Alteplase) therapy is initiated. - Current participation in another research drug treatment protocol. - Informed consent is not or cannot be obtained. For example, obtunded patients are not automatically excluded from the study. However, if the next of kin or legal guardian (i.e., the individual legally empowered in the state where the consent is obtained) cannot provide consent, randomization and entry into the study could not proceed. IMAGING Exclusion Criteria: - High density lesion consistent with hemorrhage of any degree. - Significant mass effect with midline shift. - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging. An ASPECTS of < 4can be used as a guideline when evaluating >1/3 region of territory involvement. Sulcal effacement and / or loss of grey-white differentiation alone are not contraindications for treatment.