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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00359424




Registration number
NCT00359424
Ethics application status
Date submitted
31/07/2006
Date registered
2/08/2006
Date last updated
13/12/2013

Titles & IDs
Public title
Interventional Management of Stroke (IMS) III Trial
Scientific 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
Secondary ID [1] 0 0
U01NS052220
Secondary ID [2] 0 0
U01NS052220
Universal Trial Number (UTN)
Trial acronym
IMSIII
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IV rt-PA alone
Other interventions - endovascular therapy

Active Comparator: intravenous (IV) rt-PA alone - Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

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.


Treatment: Drugs: 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 interventions: 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.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
at 90 days post randomization
Primary outcome [2] 0 0
Death Due to Any Cause
Timepoint [2] 0 0
within 90 days post randomization
Primary outcome [3] 0 0
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
Timepoint [3] 0 0
within the first 30 hours post IV rt-PA
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
within 30 hours post IV rt-PA
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
within 30 hours post IV rt-PA
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
at 24 hours post randomization
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
at 90 days post randomization
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
at 90 days post randomization
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
90 days post randomization
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
at 90 days post randomization
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
at 180 days
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
270 days
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
360 days post randomization

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
82 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital, Level 10 King George V Building, Missenden Rd - Camperdown
Recruitment hospital [2] 0 0
St. Vincent's Hospital, Clincial Trial Centre Level 5, 378 Victoria St., Darlinghurst - Sydney
Recruitment hospital [3] 0 0
Royal Melbourne Hospital, Dept. of Neurology, 4 East, Grattan St, Parkville - Victoria
Recruitment hospital [4] 0 0
Monash Medical Center, Dept. of Neurology, 246 Clayton Rd, Clayton - Victoria
Recruitment postcode(s) [1] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [2] 0 0
NSW 2010 - Sydney
Recruitment postcode(s) [3] 0 0
3050 - Victoria
Recruitment postcode(s) [4] 0 0
3168 - Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
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United States of America
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Colorado
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State/province [5] 0 0
Connecticut
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Florida
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United States of America
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Illinois
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Iowa
Country [9] 0 0
United States of America
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Kentucky
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United States of America
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Maryland
Country [11] 0 0
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Massachusetts
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United States of America
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Michigan
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Mississippi
Country [14] 0 0
United States of America
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Missouri
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United States of America
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New York
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United States of America
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North Carolina
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Ohio
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Oregon
Country [19] 0 0
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Pennsylvania
Country [20] 0 0
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South Carolina
Country [21] 0 0
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Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
France
State/province [28] 0 0
Cedex
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
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Germany
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Freiburg
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Germany
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Greifswald
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Germany
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Halle
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Germany
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Hamburg
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Netherlands
State/province [34] 0 0
Nieuwegein
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Spain
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Badalona
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Spain
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Barcelona
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Switzerland
State/province [37] 0 0
Basel
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Switzerland
State/province [38] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Joseph Broderick
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Medical University of South Carolina
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Calgary
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00359424
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joseph P. Broderick, MD
Address 0 0
Primary Neurologist Investigator, University of Cincinnati Academic Health Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00359424