Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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.
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
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
Timepoint [1] 0 0
within 30 hours post IV rt-PA
Secondary outcome [2] 0 0
Asymptomatic Intracranial Hemorrhage
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.
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.
Timepoint [4] 0 0
at 90 days post randomization
Secondary outcome [5] 0 0
Barthel Index (BI) Dichotomized 0-90 Versus 95-100
Timepoint [5] 0 0
at 90 days post randomization
Secondary outcome [6] 0 0
Trail Making Test Part A Time
Timepoint [6] 0 0
90 days post randomization
Secondary outcome [7] 0 0
Trail Making Test Part B Time
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
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
Timepoint [9] 0 0
270 days
Secondary outcome [10] 0 0
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
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
Sex
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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2013
Sample size
Target
Accrual to date
Final
656
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
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
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Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
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Massachusetts
Country [12] 0 0
United States of America
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Michigan
Country [13] 0 0
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Mississippi
Country [14] 0 0
United States of America
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Missouri
Country [15] 0 0
United States of America
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New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
South Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
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
Country [30] 0 0
Germany
State/province [30] 0 0
Freiburg
Country [31] 0 0
Germany
State/province [31] 0 0
Greifswald
Country [32] 0 0
Germany
State/province [32] 0 0
Halle
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Netherlands
State/province [34] 0 0
Nieuwegein
Country [35] 0 0
Spain
State/province [35] 0 0
Badalona
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Switzerland
State/province [37] 0 0
Basel
Country [38] 0 0
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00359424