Interventional Management of Stroke (IMS) III Trial
- Registration Number
- NCT00359424
- Lead Sponsor
- Joseph Broderick
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 656
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Endovascular therapy endovascular therapy Group two will receive a lower dose or a standard dose of IV rt-PA 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 neurointerventionalist will then choose (based on the location and extent of the blood clot) a protocol approved endovascular treatment given directly in the brain artery that will be most effective in reopening the blocked artery. Endovascular therapy IV rt-PA alone Group two will receive a lower dose or a standard dose of IV rt-PA 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 neurointerventionalist will then choose (based on the location and extent of the blood clot) a protocol approved endovascular treatment given directly in the brain artery that will be most effective in reopening the blocked artery. intravenous (IV) rt-PA alone IV rt-PA alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
- Primary Outcome Measures
Name Time Method Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2. at 90 days post randomization The modified Rankin Scale (mRS) runs from 0-6 running from perfect health without symptoms to death. 0 - No symptoms at all. 1 - No significant disability. Able to carry out all usual duties and activities. 2 - Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 - Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 - Dead. Persons with a Rankin of 0-2 are considered functionally independent.
Death Due to Any Cause within 90 days post randomization Symptomatic Intracranial Hemorrhage within the first 30 hours post IV rt-PA Symptomatic Intracranial Hemorrhage- Symptomatic ICH is defined as an intracranial hemorrhage temporally related to a decline in neurological status as well as new or worsening neurologic symptoms in the judgment of the clinical investigator and which may warrant medical intervention. These events are identified via Adverse Event CRF submitted by the site
- Secondary Outcome Measures
Name Time Method National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater. at 90 days post randomization The National Institutes of Health Stroke Scale (NIHSS), a serial measure of neurologic deficit, is a 42-point scale that quantifies neurologic deficits in 11 categories, with 0 indicating normal function without neurologic deficit and higher scores indicating greater severity of deficit.
National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater. at 24 hours post randomization The National Institutes of Health Stroke Scale (NIHSS), a serial measure of neurologic deficit, is a 42-point scale that \>\> quantifies neurologic deficits in 11 categories, with 0 indicating normal function without neurologic deficit and higher
\>\> scores indicating greater severity of deficit.Incidence of Parenchymal Type II (PH2) Hematomas within 30 hours post IV rt-PA a dense intracerebral hematoma involving more than 30% of the infarcted area with substantial space-occupying effect or any hemorrhagic area outside the infarcted area, determined via central read of the submitted CT scans.
Asymptomatic Intracranial Hemorrhage within 30 hours post IV rt-PA Asymptomatic intracranial hemorrhage is defined as an intracranial hemorrhage without evidence of decline in neurological status or new or worsening neurologic symptoms in the judgment of the clinical investigator. These events are identified via Adverse Event CRF submitted by the site.
Barthel Index (BI) Dichotomized 0-90 Versus 95-100 at 90 days post randomization The Barthel Index (BI)is an ordinal scale used to measure a subject's performance in activities of daily living (ADL) in ten variables- feeding, transfer (bed to chair), grooming, toilet use, bathing, mobility on a level surface, stair use, dressing, bowels and bladder. It is an assessment of independence in ADL and is scored in increments of 5 points. The lowest possible score on the index is 0 which implies total dependence on others for ADL and the highest total score is 100 which indicate full independent in ADL. A higher score is associated with a greater likelihood of being able to live at home with a degree of independence.
Trail Making Test Part A Time 90 days post randomization The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete each part. Normally, the entire test (A and B) can be completed in 5 to 10 minutes.
Trail Making Test Part B Time at 90 days post randomization The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete each part. Normally, the entire test (A and B) can be completed in 5 to 10 minutes.
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2 360 days post randomization The modified Rankin Scale (mRS) runs from 0-6 running from perfect health without symptoms to death. 0 - No symptoms at all. 1 - No significant disability. Able to carry out all usual duties and activities. 2 - Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 - Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 - Dead. Persons with a Rankin of 0-2 are considered functionally independent.
Trial Locations
- Locations (71)
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
PENN State M.S. Hershey Medical Center, 500 University Drive MC: HS 86, Long Lane Rom HG:212
🇺🇸Hershey, Pennsylvania, United States
UCLA Medical Center, 924 Westwood Blvd., Suite 300
🇺🇸Los Angeles, California, United States
University of Texas Medical School at Houston, 6431 Fannin, MSB 7.044
🇺🇸Houston, Texas, United States
University of Pittsburgh, Medical Center, 200 Lothrop Street, PUH C-400
🇺🇸Pittsburgh, Pennsylvania, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Royal Prince Alfred Hospital, Level 10 King George V Building, Missenden Rd
🇦🇺Camperdown, Australia
Lahey Clinic Medical Center
🇺🇸Burlington, Massachusetts, United States
University of Calgary, Calgary Health Region/Foothills Hospital, 1403 29th Street NW
🇨🇦Calgary, Alberta, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Bichat Stroke Centre
🇫🇷Paris, Cedex, France
Centre Hospital University of Montreal
🇨🇦Montreal, Quebec, Canada
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
University Hospital Basel
🇨🇭Basel, Switzerland
Centre Hospitalier, University Vaudois
🇨🇭Lausanne, Switzerland
University of British Columbia, Vancouver General Hospital, VGH Stroke Program, Gordon & Leslie Diamond Healthcare Centre, 2775 Laurel St., 8th Fl., Ste. 8295
🇨🇦Vancouver, British Columbia, Canada
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center, 222 W. Thomas Road, Suite 404
🇺🇸Phoenix, Arizona, United States
Henry Ford Hospital, 2799 W Grand Blvd, CFP-260
🇺🇸Detroit, Michigan, United States
The University Hospital, 234 Goodman Ave.
🇺🇸Cincinnati, Ohio, United States
Good Samaritan Hospital, 375 Dixmyth Ave.
🇺🇸Cincinnati, Ohio, United States
The Jewish Hospital of Cincinnati, 4777 East Galbraith Rd
🇺🇸Cincinnati, Ohio, United States
Mercy Hospital, Western Hills, 3131 Queen City Ave.
🇺🇸Cincinnati, Ohio, United States
Mercy Hospital, Mt Airy, 2446 Kipling Ave.
🇺🇸Cincinnati, Ohio, United States
Mercy Hospital Anderson, 7500 State Rd
🇺🇸Cincinnati, Ohio, United States
Froedtert Hospital, Medical College of Wisconsin, 9200 W. Wisconsin Avenue
🇺🇸Milwaukee, Wisconsin, United States
Hoag Memorial Hospital
🇺🇸Newport Beach, California, United States
Mayo Clinic Arizona, 5777 E. Mayo Blvd.
🇺🇸Scottsdale, Arizona, United States
Colorado Neurological Institute, Swedish Medical Center, 501 E. Hampden Ave.
🇺🇸Englewood, Colorado, United States
Santa Monica-UCLA Medical Center, 1250 16th Street
🇺🇸Santa Monica, California, United States
Morton Plant Mease Health Care, 300 Pinellas Street MS 49
🇺🇸Clearwater, Florida, United States
Alexian Brothers Medical Center, 800 Biesterfield Rd.
🇺🇸Elk Grove Village, Illinois, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Ruan Neurological Mercy Medical Center, 1111 6th Ave., Ste. 400
🇺🇸Des Moines, Iowa, United States
St Luke's West Hospital, 7380 Turfway Rd.
🇺🇸Florence, Kentucky, United States
St. Luke's Hospital East, 85 N. Grand Ave.
🇺🇸Ft. Thomas, Kentucky, United States
Johns Hopkins University, 1500 Orleans St. 3M South
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital, 55 Fruit Street
🇺🇸Boston, Massachusetts, United States
Michigan State University, Sparrow Hospital, B 401 Clinical Center
🇺🇸East Lansing, Michigan, United States
Washington University/Barnes Jewish Hospital, 660 S. Euclid Avenue
🇺🇸St. Louis, Missouri, United States
Suny Upstate Medical University
🇺🇸Syracuse, New York, United States
Mission Hospital, 509 Biltmore Avenue
🇺🇸Asheville, North Carolina, United States
Riverside Methodist Hospital, 3535 Olentangy River Road
🇺🇸Columbus, Ohio, United States
University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508
🇺🇸Cleveland, Ohio, United States
Mercy Hospital Fairfield, 3000 Mack Rd.
🇺🇸Fairfield, Ohio, United States
Bethesda North Hospital, 10500 Montgomery Rd.
🇺🇸Montgomery, Ohio, United States
OHSU, Oregon Stroke Center, Providence St. Vincent's Hospital, Providence Portland Hospital
🇺🇸Portland, Oregon, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Lehigh Valley Hospital Center, 1200 South Cedar Crest Blvd.
🇺🇸Allentown, Pennsylvania, United States
Allegheny General Hospital, 420 East North Avenue, East Wing Office Bldg., Suite 206
🇺🇸Pittsburgh, Pennsylvania, United States
St. Vincent's Hospital, Clincial Trial Centre Level 5, 378 Victoria St., Darlinghurst
🇦🇺Sydney, Australia
Royal Melbourne Hospital, Dept. of Neurology, 4 East, Grattan St, Parkville
🇦🇺Victoria, Australia
Monash Medical Center, Dept. of Neurology, 246 Clayton Rd, Clayton
🇦🇺Victoria, Australia
Ernst Moritz Arndt University
🇩🇪Greifswald, Germany
University of Freiburg
🇩🇪Freiburg, Germany
Technische Universität, Dresden
🇩🇪Dresden, Germany
St. Antonius Hospital
🇳🇱Nieuwegein, Netherlands
Asklepios Klinik Nord Heidberg
🇩🇪Hamburg, Germany
Hospital Vall d´Hebron
🇪🇸Barcelona, Spain
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Stroke Center at Hartford, 80 Seymour St. Rm JB603
🇺🇸Hartford, Connecticut, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
St. Elizabeth Medical Center South, One Medical Village Drive
🇺🇸Edgewood, Kentucky, United States
The Christ Hospital, 2139 Auburn Ave.
🇺🇸Cincinnati, Ohio, United States
The Ottawa Hospital, Civic Campus, CPC Main, RM 36, Box 608, 1053 Carling Avenue
🇨🇦Ottawa, Ontario, Canada
Toronto Western Hospital, 5th Floor Rm. 447, 399 Bathurst St.
🇨🇦Toronto, Ontario, Canada
Martin-Luther University
🇩🇪Halle, Germany
University of Louisville, Kentucky Neuroscience Research, Stroke Research, 401 East Chestnut Street, Suite 520
🇺🇸Louisville, Kentucky, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of North Carolina, CB # 7025, 7003 Neurosciences Hospital, 7th Floor
🇺🇸Chapel Hill, North Carolina, United States
University Medical Center at Brackenridge Hospital
🇺🇸Austin, Texas, United States