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

Interventional Management of Stroke Trial (IMS III): A Phase III Clinical Trial Examining Whether a Combined Intravenous (IV) and Intra-Arterial (IA) Approach to Recanalization is Superior to Standard IV Rt-PA (Activase®) Alone

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.

Study Overview

• Status: Terminated
• Conditions: Stroke
• Intervention / Treatment: Drug: IV rt-PA alone; Other: endovascular therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 656
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, NSW 2050
    • Royal Prince Alfred Hospital, Level 10 King George V Building, Missenden Rd
  • Sydney, Australia, NSW 2010
    • St. Vincent's Hospital, Clincial Trial Centre Level 5, 378 Victoria St., Darlinghurst
  • Victoria, Australia, 3050
    • Royal Melbourne Hospital, Dept. of Neurology, 4 East, Grattan St, Parkville
  • Victoria, Australia, 3168
    • Monash Medical Center, Dept. of Neurology, 246 Clayton Rd, Clayton
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • University of Calgary, Calgary Health Region/Foothills Hospital, 1403 29th Street NW
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • University of British Columbia, Vancouver General Hospital, VGH Stroke Program, Gordon & Leslie Diamond Healthcare Centre, 2775 Laurel St., 8th Fl., Ste. 8295
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital, Civic Campus, CPC Main, RM 36, Box 608, 1053 Carling Avenue
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital, 5th Floor Rm. 447, 399 Bathurst St.
  • Quebec
    • Montreal, Quebec, Canada, H2L4M1
      • Centre Hospital University of Montreal
• France
  • Cedex
    • Paris, Cedex, France, 75018
      • Bichat Stroke Centre
• Germany
  • Dresden, Germany, 01307
    • Technische Universität, Dresden
  • Freiburg, Germany, 79106
    • University of Freiburg
  • Greifswald, Germany, 17475
    • Ernst Moritz Arndt University
  • Halle, Germany, 06120
    • Martin-Luther University
  • Hamburg, Germany, 22417
    • Asklepios Klinik Nord Heidberg
• Netherlands
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Hospital
• Spain
  • Badalona, Spain, 8916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 8035
    • Hospital Vall D´Hebron
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier, University Vaudois
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center, 222 W. Thomas Road, Suite 404
    • Scottsdale, Arizona, United States, 85054
      • Mayo Clinic Arizona, 5777 E. Mayo Blvd.
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Medical Center, 924 Westwood Blvd., Suite 300
    • Newport Beach, California, United States, 92658
      • Hoag Memorial Hospital
    • Santa Monica, California, United States, 90404
      • Santa Monica-UCLA Medical Center, 1250 16th Street
  • Colorado
    • Englewood, Colorado, United States, 80113-2771
      • Colorado Neurological Institute, Swedish Medical Center, 501 E. Hampden Ave.
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Stroke Center at Hartford, 80 Seymour St. Rm JB603
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Mease Health Care, 300 Pinellas Street MS 49
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical Center, 800 Biesterfield Rd.
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Ruan Neurological Mercy Medical Center, 1111 6th Ave., Ste. 400
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • St. Elizabeth Medical Center South, One Medical Village Drive
    • Florence, Kentucky, United States, 41042
      • St Luke's West Hospital, 7380 Turfway Rd.
    • Ft. Thomas, Kentucky, United States, 41075
      • St. Luke's Hospital East, 85 N. Grand Ave.
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, Kentucky Neuroscience Research, Stroke Research, 401 East Chestnut Street, Suite 520
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University, 1500 Orleans St. 3M South
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, 55 Fruit Street
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital, 2799 W Grand Blvd, CFP-260
    • East Lansing, Michigan, United States, 48824
      • Michigan State University, Sparrow Hospital, B 401 Clinical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University/Barnes Jewish Hospital, 660 S. Euclid Avenue
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • Suny Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital, 509 Biltmore Avenue
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, CB # 7025, 7003 Neurosciences Hospital, 7th Floor
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital, 2139 Auburn Ave.
    • Cincinnati, Ohio, United States, 45238
      • Mercy Hospital, Western Hills, 3131 Queen City Ave.
    • Cincinnati, Ohio, United States, 45239
      • Mercy Hospital, Mt Airy, 2446 Kipling Ave.
    • Cincinnati, Ohio, United States, 45219
      • The University Hospital, 234 Goodman Ave.
    • Cincinnati, Ohio, United States, 45220-2489
      • Good Samaritan Hospital, 375 Dixmyth Ave.
    • Cincinnati, Ohio, United States, 45236
      • The Jewish Hospital of Cincinnati, 4777 East Galbraith Rd
    • Cincinnati, Ohio, United States, 45255
      • Mercy Hospital Anderson, 7500 State Rd
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital, 3535 Olentangy River Road
    • Fairfield, Ohio, United States, 45014
      • Mercy Hospital Fairfield, 3000 Mack Rd.
    • Montgomery, Ohio, United States, 45242
      • Bethesda North Hospital, 10500 Montgomery Rd.
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU, Oregon Stroke Center, Providence St. Vincent's Hospital, Providence Portland Hospital
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital Center, 1200 South Cedar Crest Blvd.
    • Hershey, Pennsylvania, United States, 17033
      • PENN State M.S. Hershey Medical Center, 500 University Drive MC: HS 86, Long Lane Rom HG:212
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital, 420 East North Avenue, East Wing Office Bldg., Suite 206
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh, Medical Center, 200 Lothrop Street, PUH C-400
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78701
      • University Medical Center at Brackenridge Hospital
    • Houston, Texas, United States, 77030
      • University of Texas Medical School at Houston, 6431 Fannin, MSB 7.044
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital, Medical College of Wisconsin, 9200 W. Wisconsin Avenue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 82 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: intravenous (IV) rt-PA alone; Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.	Drug: IV rt-PA alone; Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy; Group one will receive the standard dose of IV rt-PA given over an hour.; Other Names: Activase®, Actilyse®
Experimental: 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.	Drug: IV rt-PA alone; Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy; Group one will receive the standard dose of IV rt-PA given over an hour.; Other Names: Activase®, Actilyse®; Other: endovascular therapy; Group two will receive a lower dose or the 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 a protocol approved endovascular treatment given directly in the brain artery that will be most effective in reopening the blocked artery. Endovascular therapy can be implemented with or without interarterial rt-PA use.; Other Names: Activase®, Actilyse®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2.	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.	at 90 days post randomization
Death Due to Any Cause		within 90 days post randomization
Symptomatic Intracranial Hemorrhage	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	within the first 30 hours post IV rt-PA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Parenchymal Type II (PH2) Hematomas	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.	within 30 hours post IV rt-PA
Asymptomatic Intracranial Hemorrhage	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.	within 30 hours post IV rt-PA
National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater.	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.	at 24 hours post randomization
National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater.	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.	at 90 days post randomization
Barthel Index (BI) Dichotomized 0-90 Versus 95-100	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.	at 90 days post randomization
Trail Making Test Part A Time	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.	90 days post randomization
Trail Making Test Part B Time	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.	at 90 days post randomization
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2	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.	at 180 days
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2	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.	270 days
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2	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.	360 days post randomization

Collaborators and Investigators

• Sponsor: Joseph Broderick
• Collaborators: Medical University of South Carolina; National Institute of Neurological Disorders and Stroke (NINDS); University of Calgary
• Investigators: Principal Investigator: Joseph P. Broderick, MD, Primary Neurologist Investigator, University of Cincinnati Academic Health Center; Principal Investigator: Thomas A. Tomsick, MD, Primary Interventional Investigator, University of Cincinnati Academic Health Center

Publications and helpful links

General Publications

• van der Ende NA, Roozenbeek B, Broderick JP, Khatri P, Lingsma HF, Dippel DW. Blinding of outcome assessors and its association with outcome in a randomized open-label stroke trial. Int J Stroke. 2022 Oct 19:17474930221131706. doi: 10.1177/17474930221131706. Online ahead of print.
• Chalos V, van der Ende NAM, Lingsma HF, Mulder MJHL, Venema E, Dijkland SA, Berkhemer OA, Yoo AJ, Broderick JP, Palesch YY, Yeatts SD, Roos YBWEM, van Oostenbrugge RJ, van Zwam WH, Majoie CBLM, van der Lugt A, Roozenbeek B, Dippel DWJ; MR CLEAN Investigators. National Institutes of Health Stroke Scale: An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke. Stroke. 2020 Jan;51(1):282-290. doi: 10.1161/STROKEAHA.119.026791. Epub 2019 Dec 4.
• Simpson KN, Simpson AN, Mauldin PD, Palesch YY, Yeatts SD, Kleindorfer D, Tomsick TA, Foster LD, Demchuk AM, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, von Kummer R, Molina CA, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Broderick JP; Interventional Management of Stroke (IMS) III Investigators. Observed Cost and Variations in Short Term Cost-Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III. J Am Heart Assoc. 2017 May 8;6(5):e004513. doi: 10.1161/JAHA.116.004513.
• Venema E, Mulder MJHL, Roozenbeek B, Broderick JP, Yeatts SD, Khatri P, Berkhemer OA, Emmer BJ, Roos YBWEM, Majoie CBLM, van Oostenbrugge RJ, van Zwam WH, van der Lugt A, Steyerberg EW, Dippel DWJ, Lingsma HF. Selection of patients for intra-arterial treatment for acute ischaemic stroke: development and validation of a clinical decision tool in two randomised trials. BMJ. 2017 May 3;357:j1710. doi: 10.1136/bmj.j1710.
• Mulder MJ, Venema E, Roozenbeek B, Broderick JP, Yeatts SD, Khatri P, Berkhemer OA, Roos YB, Majoie CB, van Oostenbrugge RJ, van Zwam WH, van der Lugt A, Steyerberg EW, Dippel DW, Lingsma HF. Towards personalised intra-arterial treatment of patients with acute ischaemic stroke: a study protocol for development and validation of a clinical decision aid. BMJ Open. 2017 Mar 22;7(3):e013699. doi: 10.1136/bmjopen-2016-013699.
• Broderick JP, Berkhemer OA, Palesch YY, Dippel DW, Foster LD, Roos YB, van der Lugt A, Tomsick TA, Majoie CB, van Zwam WH, Demchuk AM, van Oostenbrugge RJ, Khatri P, Lingsma HF, Hill MD, Roozenbeek B, Jauch EC, Jovin TG, Yan B, von Kummer R, Molina CA, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson CS, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Simpson KN; IMS III Investigators; MR CLEAN Investigators. Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data. Stroke. 2015 Dec;46(12):3416-22. doi: 10.1161/STROKEAHA.115.011397. Epub 2015 Oct 20. Erratum In: Stroke. 2016 Jan;47(1):e21. IMS II [corrected to IMS III Investigators].
• Abou-Chebl A, Yeatts SD, Yan B, Cockroft K, Goyal M, Jovin T, Khatri P, Meyers P, Spilker J, Sugg R, Wartenberg KE, Tomsick T, Broderick J, Hill MD. Impact of General Anesthesia on Safety and Outcomes in the Endovascular Arm of Interventional Management of Stroke (IMS) III Trial. Stroke. 2015 Aug;46(8):2142-8. doi: 10.1161/STROKEAHA.115.008761. Epub 2015 Jul 2.
• Al-Ali F, Elias JJ, Tomsick TA, Liebeskind DS, Broderick JP; IMS Study Groups. Relative Influence of Capillary Index Score, Revascularization, and Time on Stroke Outcomes From the Interventional Management of Stroke III Trial. Stroke. 2015 Jun;46(6):1590-4. doi: 10.1161/STROKEAHA.115.009066. Epub 2015 May 7.
• Palesch YY, Yeatts SD, Tomsick TA, Foster LD, Demchuk AM, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, von Kummer R, Molina CA, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Simpson A, Simpson KN, Broderick JP; Interventional Management of Stroke III Investigators. Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial. Stroke. 2015 May;46(5):1321-7. doi: 10.1161/STROKEAHA.115.009180. Epub 2015 Apr 9.
• Menon BK, Qazi E, Nambiar V, Foster LD, Yeatts SD, Liebeskind D, Jovin TG, Goyal M, Hill MD, Tomsick TA, Broderick JP, Demchuk AM; Interventional Management of Stroke III Investigators. Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial. Stroke. 2015 May;46(5):1239-44. doi: 10.1161/STROKEAHA.115.009009. Epub 2015 Mar 19.
• Tomsick TA, Yeatts SD, Liebeskind DS, Carrozzella J, Foster L, Goyal M, von Kummer R, Hill MD, Demchuk AM, Jovin T, Yan B, Zaidat OO, Schonewille W, Engelter S, Martin R, Khatri P, Spilker J, Palesch YY, Broderick JP; IMS III Investigators. Endovascular revascularization results in IMS III: intracranial ICA and M1 occlusions. J Neurointerv Surg. 2015 Nov;7(11):795-802. doi: 10.1136/neurintsurg-2014-011318. Epub 2014 Oct 23.
• Simpson KN, Simpson AN, Mauldin PD, Hill MD, Yeatts SD, Spilker JA, Foster LD, Khatri P, Martin R, Jauch EC, Kleindorfer D, Palesch YY, Broderick JP; IMS III Investigators. Drivers of costs associated with reperfusion therapy in acute stroke: the Interventional Management of Stroke III Trial. Stroke. 2014 Jun;45(6):1791-8. doi: 10.1161/STROKEAHA.113.003874. Epub 2014 May 13.
• Goyal M, Almekhlafi MA, Fan L, Menon BK, Demchuk AM, Yeatts SD, Hill MD, Tomsick T, Khatri P, Zaidat OO, Jauch EC, Eesa M, Jovin TG, Broderick JP. Evaluation of interval times from onset to reperfusion in patients undergoing endovascular therapy in the Interventional Management of Stroke III trial. Circulation. 2014 Jul 15;130(3):265-72. doi: 10.1161/CIRCULATIONAHA.113.007826. Epub 2014 May 9.
• Yeatts SD, Martin RH, Coffey CS, Lyden PD, Foster LD, Woolson RF, Broderick JP, Di Tullio MR, Jungreis CA, Palesch YY; IMS III Investigators. Challenges of decision making regarding futility in a randomized trial: the Interventional Management of Stroke III experience. Stroke. 2014 May;45(5):1408-14. doi: 10.1161/STROKEAHA.113.003925. Epub 2014 Apr 3.
• Liebeskind DS, Tomsick TA, Foster LD, Yeatts SD, Carrozzella J, Demchuk AM, Jovin TG, Khatri P, von Kummer R, Sugg RM, Zaidat OO, Hussain SI, Goyal M, Menon BK, Al Ali F, Yan B, Palesch YY, Broderick JP; IMS III Investigators. Collaterals at angiography and outcomes in the Interventional Management of Stroke (IMS) III trial. Stroke. 2014 Mar;45(3):759-64. doi: 10.1161/STROKEAHA.113.004072. Epub 2014 Jan 28.
• Hill MD, Demchuk AM, Goyal M, Jovin TG, Foster LD, Tomsick TA, von Kummer R, Yeatts SD, Palesch YY, Broderick JP; IMS3 Investigators. Alberta Stroke Program early computed tomography score to select patients for endovascular treatment: Interventional Management of Stroke (IMS)-III Trial. Stroke. 2014 Feb;45(2):444-9. doi: 10.1161/STROKEAHA.113.003580. Epub 2013 Dec 12.
• Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013 Mar 7;368(10):893-903. doi: 10.1056/NEJMoa1214300. Epub 2013 Feb 7. Erratum In: N Engl J Med. 2013 Mar 28;368(13):1265.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: July 31, 2006
• First Submitted That Met QC Criteria: July 31, 2006
• First Posted (Estimate): August 2, 2006

Study Record Updates

• Last Update Posted (Estimate): December 13, 2013
• Last Update Submitted That Met QC Criteria: November 19, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: stroke; acute ischemic stroke; blood clot; thrombolytic; recombinant tissue plasminogen activator; rt-PA; recanalization; clot-dissolving; Activase®; Actilyse®; Concentric Merci® Retriever; EKOS® Micro-Infusion catheter (MicroLysus); The Penumbra System™; Standard microcatheter
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: U01NS052220 (U.S. NIH Grant/Contract); U01NS054630 (U.S. NIH Grant/Contract); 2009-017454-12 (EudraCT Number)