AzTrials
AzTrials

StrokePhase 3IMSIIINCT00359424

Interventional Management of Stroke (IMS) III Trial

A Phase 3 study testing IV rt-PA alone and endovascular therapy in people with Stroke, run by Joseph Broderick at 71 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 82 years
Conditions the study is for
Stroke
What is being tested?
IV rt-PA alone and endovascular therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
656 participants
Where
71 sitesin 8 countries
Study dates
Aug 2006to Apr 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 82 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 28Show fewer
  • 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

Trial locations and contacts

71 sites in 8 countries.

71 sites in 8 countries

United States49 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Lehigh Valley Hospital Center, 1200 South Cedar Crest Blvd.

    Allentown, Pennsylvania, 18103

  • Mission Hospital, 509 Biltmore Avenue

    Asheville, North Carolina, 28801

  • University Medical Center at Brackenridge Hospital

    Austin, Texas, 78701

  • Johns Hopkins University, 1500 Orleans St. 3M South

    Baltimore, Maryland, 21231

  • University of Alabama Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital, 55 Fruit Street

    Boston, Massachusetts, 02114

  • Lahey Clinic Medical Center

    Burlington, Massachusetts, 01805

  • University of North Carolina, CB # 7025, 7003 Neurosciences Hospital, 7th Floor

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • The Christ Hospital, 2139 Auburn Ave.

    Cincinnati, Ohio, 45219

  • The University Hospital, 234 Goodman Ave.

    Cincinnati, Ohio, 45219

  • Good Samaritan Hospital, 375 Dixmyth Ave.

    Cincinnati, Ohio, 45220-2489

  • The Jewish Hospital of Cincinnati, 4777 East Galbraith Rd

    Cincinnati, Ohio, 45236

  • Mercy Hospital, Western Hills, 3131 Queen City Ave.

    Cincinnati, Ohio, 45238

  • Mercy Hospital, Mt Airy, 2446 Kipling Ave.

    Cincinnati, Ohio, 45239

  • Mercy Hospital Anderson, 7500 State Rd

    Cincinnati, Ohio, 45255

  • Morton Plant Mease Health Care, 300 Pinellas Street MS 49

    Clearwater, Florida, 33756

  • University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508

    Cleveland, Ohio, 44106

  • Riverside Methodist Hospital, 3535 Olentangy River Road

    Columbus, Ohio, 43214

  • Ruan Neurological Mercy Medical Center, 1111 6th Ave., Ste. 400

    Des Moines, Iowa, 50314

  • Henry Ford Hospital, 2799 W Grand Blvd, CFP-260

    Detroit, Michigan, 48202

  • Michigan State University, Sparrow Hospital, B 401 Clinical Center

    East Lansing, Michigan, 48824

  • St. Elizabeth Medical Center South, One Medical Village Drive

    Edgewood, Kentucky, 41017

  • Alexian Brothers Medical Center, 800 Biesterfield Rd.

    Elk Grove Village, Illinois, 60007

  • Colorado Neurological Institute, Swedish Medical Center, 501 E. Hampden Ave.

    Englewood, Colorado, 80113-2771

  • Mercy Hospital Fairfield, 3000 Mack Rd.

    Fairfield, Ohio, 45014

  • St Luke's West Hospital, 7380 Turfway Rd.

    Florence, Kentucky, 41042

  • St. Luke's Hospital East, 85 N. Grand Ave.

    Fort Thomas, Kentucky, 41075

  • Stroke Center at Hartford, 80 Seymour St. Rm JB603

    Hartford, Connecticut, 06102

  • PENN State M.S. Hershey Medical Center, 500 University Drive MC: HS 86, Long Lane Rom HG:212

    Hershey, Pennsylvania, 17033

  • University of Texas Medical School at Houston, 6431 Fannin, MSB 7.044

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • UCLA Medical Center, 924 Westwood Blvd., Suite 300

    Los Angeles, California, 90024

  • University of Louisville, Kentucky Neuroscience Research, Stroke Research, 401 East Chestnut Street, Suite 520

    Louisville, Kentucky, 40202

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Froedtert Hospital, Medical College of Wisconsin, 9200 W. Wisconsin Avenue

    Milwaukee, Wisconsin, 53226

  • Bethesda North Hospital, 10500 Montgomery Rd.

    Montgomery, Ohio, 45242

  • Hoag Memorial Hospital

    Newport Beach, California, 92658

  • Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center, 222 W. Thomas Road, Suite 404

    Phoenix, Arizona, 85013

  • Allegheny General Hospital, 420 East North Avenue, East Wing Office Bldg., Suite 206

    Pittsburgh, Pennsylvania, 15212

  • University of Pittsburgh, Medical Center, 200 Lothrop Street, PUH C-400

    Pittsburgh, Pennsylvania, 15213

  • OHSU, Oregon Stroke Center, Providence St. Vincent's Hospital, Providence Portland Hospital

    Portland, Oregon, 97239

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Santa Monica-UCLA Medical Center, 1250 16th Street

    Santa Monica, California, 90404

  • Mayo Clinic Arizona, 5777 E. Mayo Blvd.

    Scottsdale, Arizona, 85054

  • Washington University/Barnes Jewish Hospital, 660 S. Euclid Avenue

    St Louis, Missouri, 63110

  • Suny Upstate Medical University

    Syracuse, New York, 13210

Other trials in United States

Canada7 sites

  • University of Calgary, Calgary Health Region/Foothills Hospital, 1403 29th Street NW

    Calgary, Alberta, T2N 2T9

  • Centre Hospital University of Montreal

    Montreal, Quebec, H2L4M1

  • The Ottawa Hospital, Civic Campus, CPC Main, RM 36, Box 608, 1053 Carling Avenue

    Ottawa, Ontario, K1Y 4E9

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Toronto Western Hospital, 5th Floor Rm. 447, 399 Bathurst St.

    Toronto, Ontario, M5T 2S8

  • 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, V5Z 1M9

Other trials in Canada

Germany5 sites

  • Technische Universität, Dresden

    Dresden, 01307

  • University of Freiburg

    Freiburg im Breisgau, 79106

  • Ernst Moritz Arndt University

    Greifswald, 17475

  • Martin-Luther University

    Halle, 06120

  • Asklepios Klinik Nord Heidberg

    Hamburg, 22417

Other trials in Germany

Australia4 sites

  • Royal Prince Alfred Hospital, Level 10 King George V Building, Missenden Rd

    Camperdown, NSW 2050

  • St. Vincent's Hospital, Clincial Trial Centre Level 5, 378 Victoria St., Darlinghurst

    Sydney, NSW 2010

  • Royal Melbourne Hospital, Dept. of Neurology, 4 East, Grattan St, Parkville

    Victoria, 3050

  • Monash Medical Center, Dept. of Neurology, 246 Clayton Rd, Clayton

    Victoria, 3168

Other trials in Australia

Spain2 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona, 8916

  • Hospital Vall d´Hebron

    Barcelona, 8035

Other trials in Spain

Switzerland2 sites

  • University Hospital Basel

    Basel, 4031

  • Centre Hospitalier, University Vaudois

    Lausanne, 1011

Other trials in Switzerland

France1 site

  • Bichat Stroke Centre

    Paris, Cedex, 75018

Other trials in France

Netherlands1 site

  • St. Antonius Hospital

    Nieuwegein, 3435 CM

Other trials in Netherlands

About this study

Official title: 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.

Read the 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.

Conditions
Stroke
Being tested
IV rt-PA alone, endovascular therapy
Keywords
acute ischemic stroke, rt-PA, thrombolytic, recombinant tissue plasminogen activator, recanalization, blood clot, stroke, clot-dissolving, Activase®, Actilyse®, Concentric Merci® Retriever, EKOS® Micro-Infusion catheter (MicroLysus), The Penumbra System™, Standard microcatheter
Medical subject headings
Stroke, Ischemic Stroke, Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IV rt-PA aloneDrug

    Also called Activase®, Actilyse®

    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.

  • endovascular therapyOther

    Also called Activase®, Actilyse®

    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.

Study groups in NCT00359424
Study groupRoleWhat they receive
intravenous (IV) rt-PA aloneActive comparatorGroup one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
Receives: Drug: IV rt-PA alone
Endovascular therapyExperimentalGroup 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.
Receives: Drug: IV rt-PA alone; Other: endovascular therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: at 90 days post randomization

  2. Death Due to Any Cause

    Measured: within 90 days post randomization

  3. 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

    Measured: within the first 30 hours post IV rt-PA

Secondary outcomes (10)

  1. 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.

    Measured: within 30 hours post IV rt-PA

  2. 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.

    Measured: within 30 hours post IV rt-PA

  3. 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.

    Measured: at 24 hours post randomization

  4. 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.

    Measured: at 90 days post randomization

  5. 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.

    Measured: at 90 days post randomization

  6. 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.

    Measured: 90 days post randomization

  7. 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.

    Measured: at 90 days post randomization

  8. 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.

    Measured: at 180 days

  9. 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.

    Measured: 270 days

  10. 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.

    Measured: 360 days post randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionJul 2012
  4. Study completionApr 2013

Why it stopped: NINDS/NIH-DSMB recommended halting trial due to futility, no safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
656 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00359424
Sponsor's protocol ID
U01NS052220
Other IDs
U01NS052220, U01NS054630, 2009-017454-12
Acronym
IMSIII
Status last verified
Nov 2013
First submitted
31 Jul 2006
Last updated
13 Dec 2013
Data monitoring committee
Yes

Publications

  • van der Ende NAM, den Hartog SJ, Broderick JP, Khatri P, Visser-Meily JMA, van Leeuwen N, Lingsma HF, Roozenbeek B, Dippel DWJ; IMS III Investigators. Disentangling the Association Between Neurologic Deficits, Patient-Reported Impairments, and Quality of Life After Ischemic Stroke. Neurology. 2023 Mar 28;100(13):e1321-e1328. doi: 10.1212/WNL.0000000000206747. Epub 2023 Jan 4.

    PubMed 36599699

  • 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. 2023 Jun;18(5):562-568. doi: 10.1177/17474930221131706. Epub 2022 Oct 19.

    PubMed 36169032

  • 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.

    PubMed 31795895

  • 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.

    PubMed 28483774

  • 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.

    PubMed 28468840

  • 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.

    PubMed 28336740

  • 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.

    PubMed 26486865

  • 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.

    PubMed 26138125

  • 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.

    PubMed 25953374

  • 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.

    PubMed 25858239

  • 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.

    PubMed 25791716

  • 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.

    PubMed 25342652

  • 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.

    PubMed 24876261

  • 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.

    PubMed 24815501

  • 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.

    PubMed 24699059

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IV rt-PA alone and endovascular therapy in people with Stroke, run by Joseph Broderick at 71 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in United States, Canada, Germany, Australia, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2. (time frame: at 90 days post randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00359424, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in