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IMSIII: Interventional Management of Stroke (IMS) III Trial

Sponsor
Joseph Broderick (Other)
Overall Status
Terminated
CT.gov ID
NCT00359424
Collaborator
National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Medical University of South Carolina (Other), University of Calgary (Other)
656
Enrollment
71
Locations
2
Arms
80
Duration (Months)
9.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: IV rt-PA alone
  • Other: endovascular therapy
 Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
656 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Aug 1, 2006
Actual Primary Completion Date :
Jul 1, 2012
Actual Study Completion Date :
Apr 1, 2013

Arms and Interventions

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®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2. [at 90 days post randomization]

      The modified Rankin Scale (mRS) runs from 0-6 running from perfect health without symptoms to death. 0 - No symptoms at all. 1 - No significant disability. Able to carry out all usual duties and activities. 2 - Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 - Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 - Dead. Persons with a Rankin of 0-2 are considered functionally independent.

    2. Death Due to Any Cause [within 90 days post randomization]

    3. Symptomatic Intracranial Hemorrhage [within the first 30 hours post IV rt-PA]

      Symptomatic Intracranial Hemorrhage- Symptomatic ICH is defined as an intracranial hemorrhage temporally related to a decline in neurological status as well as new or worsening neurologic symptoms in the judgment of the clinical investigator and which may warrant medical intervention. These events are identified via Adverse Event CRF submitted by the site

    Secondary Outcome Measures

    1. Incidence of Parenchymal Type II (PH2) Hematomas [within 30 hours post IV rt-PA]

      a dense intracerebral hematoma involving more than 30% of the infarcted area with substantial space-occupying effect or any hemorrhagic area outside the infarcted area, determined via central read of the submitted CT scans.

    2. Asymptomatic Intracranial Hemorrhage [within 30 hours post IV rt-PA]

      Asymptomatic intracranial hemorrhage is defined as an intracranial hemorrhage without evidence of decline in neurological status or new or worsening neurologic symptoms in the judgment of the clinical investigator. These events are identified via Adverse Event CRF submitted by the site.

    3. National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater. [at 24 hours post randomization]

      The National Institutes of Health Stroke Scale (NIHSS), a serial measure of neurologic deficit, is a 42-point scale that >> quantifies neurologic deficits in 11 categories, with 0 indicating normal function without neurologic deficit and higher >> scores indicating greater severity of deficit.

    4. National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater. [at 90 days post randomization]

      The National Institutes of Health Stroke Scale (NIHSS), a serial measure of neurologic deficit, is a 42-point scale that quantifies neurologic deficits in 11 categories, with 0 indicating normal function without neurologic deficit and higher scores indicating greater severity of deficit.

    5. Barthel Index (BI) Dichotomized 0-90 Versus 95-100 [at 90 days post randomization]

      The Barthel Index (BI)is an ordinal scale used to measure a subject's performance in activities of daily living (ADL) in ten variables- feeding, transfer (bed to chair), grooming, toilet use, bathing, mobility on a level surface, stair use, dressing, bowels and bladder. It is an assessment of independence in ADL and is scored in increments of 5 points. The lowest possible score on the index is 0 which implies total dependence on others for ADL and the highest total score is 100 which indicate full independent in ADL. A higher score is associated with a greater likelihood of being able to live at home with a degree of independence.

    6. Trail Making Test Part A Time [90 days post randomization]

      The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete each part. Normally, the entire test (A and B) can be completed in 5 to 10 minutes.

    7. Trail Making Test Part B Time [at 90 days post randomization]

      The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete each part. Normally, the entire test (A and B) can be completed in 5 to 10 minutes.

    8. Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2 [at 180 days]

      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.

    9. Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2 [270 days]

      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.

    10. Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2 [360 days post randomization]

      The modified Rankin Scale (mRS) runs from 0-6 running from perfect health without symptoms to death. 0 - No symptoms at all. 1 - No significant disability. Able to carry out all usual duties and activities. 2 - Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 - Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 - Dead. Persons with a Rankin of 0-2 are considered functionally independent.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 82 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Joseph Broderick
    • National Institute of Neurological Disorders and Stroke (NINDS)
    • Medical University of South Carolina
    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Joseph Broderick, Professor and Chairman Department of Neurology, University of Cincinnati
    ClinicalTrials.gov Identifier:
    NCT00359424
    Other Study ID Numbers:
    • U01NS052220
    • U01NS052220
    • U01NS054630
    • 2009-017454-12
    First Posted:
    Aug 2, 2006
    Last Update Posted:
    Dec 13, 2013
    Last Verified:
    Nov 1, 2013
    Keywords provided by Joseph Broderick, Professor and Chairman Department of Neurology, University of Cincinnati
    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
    Additional relevant MeSH terms:
    Stroke
    Tissue Plasminogen Activator

    Study Results

    Participant Flow

    Recruitment Details A total of 656 participants underwent randomization participants to endovascular therapy >> and 222 to intravenous t-PA alone) at 58 study >> centers between August 25, 2006, and April 17, >> 2012 in the United States (41 sites), Canada (7), >> Australia (4), and Europe (6)
    Pre-assignment Detail
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description Endovascular therapy (group two) received a lower dose (0.09mg per kg bolus and 0.54mg/kilogram infusion over 40 minutes, maximum dose 53.6mg) or after Amendment #5, a standard dose of IV rt-PA (.9mg/kg with 10% as a bolus and the remainder over one hour) and then underwent an angiogram test (cerebral angiography) right after the medicine was given to check for blood clots. If a clot was not seen, then no more treatment was given. If a clot was seen, the neurointerventionalist chose (based on the location and extent of the blood clot) a protocol approved endovascular treatment given directly in the brain artery that would be most effective in reopening the blocked artery. IV rt-PA alone (group one) received the standard dose (.9mg per kilogram with 10% as a bolus and the remainder as an infusion over 1 hour -maximum dose 90mg) of intravenous (IV) rt-PA alone.
    Period Title: Overall Study
    STARTED 434 222
    90 Day Follow up 343 172
    180 Day Follow up 325 167
    270 Day Follow up 313 159
    COMPLETED 304 155
    NOT COMPLETED 130 67

    Baseline Characteristics

    Arm/Group Title Endovascular Therapy IV Rt-PA Alone Total
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour. Total of all reporting groups
    Overall Participants 434 222 656
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    69
    68
    69
    Sex: Female, Male (Count of Participants)
    Female
    216
    49.8%
    100
    45%
    316
    48.2%
    Male
    218
    50.2%
    122
    55%
    340
    51.8%
    NIHSS Score (Score on a scale) [Median (Full Range) ]
    Median (Full Range) [Score on a scale]
    17
    16
    17
    Time from stroke onset to initiation of IV rt-PA (minutes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [minutes]
    122.4
    (33.7)
    121.2
    (33.8)
    122.0
    (33.7)
    NIHSS Score Strata (participants) [Number]
    NIHSS Score <20
    302
    69.6%
    150
    67.6%
    452
    68.9%
    NIHSS Score > = 20
    132
    30.4%
    72
    32.4%
    204
    31.1%

    Outcome Measures

    1. Primary Outcome
    Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2.
    Description 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.
    Time Frame at 90 days post randomization

    Outcome Measure Data

    Analysis Population Description
    The primary analysis was conducted according to intention to treat. All subjects were analyzed in the treatment group to which they were randomized. Subjects with missing mRS (n=9 in group two; n=4 in group one) or mRS assessed <60 days or >120 days post-randomization (n=10 in group two; n=4 in group one) are assigned an unfavorable outcome(mRS >2)
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    mRS 0-2
    177
    40.8%
    86
    38.7%
    mRS 3-6
    257
    59.2%
    136
    61.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Endovascular Therapy, IV Rt-PA Alone
    Comments Test of null hypothesis (equal proportions of subjects with mRS of 0-2 at 90 days post-randomization in IV Only and Endovascular treatment arms) versus alternative hypothesis (unequal proportions of subjects with mRS of 0-2 at 90 days post-randomization in IV Only and Endovascular treatment arms).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value .7031
    Comments The CMH statistic is tested at the two-sided alpha level of 0.05. For the interim analyses of the primary efficacy analysis, the alpha spending function method (Lan and DeMets, 1987) with O'Brien and Fleming (1979) stopping boundaries were adopted.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel (CMH) test adjusting for the dichotomized baseline NIHSS score (<20 or ≥20).
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 1.5
    Confidence Interval (2-Sided) 95%
    -6.1 to 9.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Positive adjusted risk difference indicates greater risk in the Endovascular group, while negative adjusted risk difference indicates greater risk in the IV Only group.
    2. Primary Outcome
    Title Death Due to Any Cause
    Description
    Time Frame within 90 days post randomization

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis includes all subjects who were randomized, and each subject analyzed according to the treatment group to which they were randomly assigned. Subjects who ended the study prior to 90 days post- randomization for a reason other than death (LTFU etc) (n=8 in group two; n=2 in group one) are assumed to be alive
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    Number [participants]
    83
    19.1%
    48
    21.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Endovascular Therapy, IV Rt-PA Alone
    Comments Test of null hypothesis (equal proportions of subjects with mortality within 90 days post-randomization in IV Only and Endovascular treatment arms) versus alternative hypothesis (unequal proportions of subjects with mortality within 90 days post-randomization in IV Only and Endovascular treatment arms).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value .5241
    Comments The CMH statistic is tested at the two-sided alpha level of 0.01.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel (CMH) test adjusting for the dichotomized baseline NIHSS score (<20 or ≥20).
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -2.0
    Confidence Interval (2-Sided) 99%
    -10.3 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Positive adjusted risk difference indicates greater risk in the Endovascular group, while negative adjusted risk difference indicates greater risk in the IV Only group.
    3. Primary Outcome
    Title Symptomatic Intracranial Hemorrhage
    Description 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
    Time Frame within the first 30 hours post IV rt-PA

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned.
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    Number [participants]
    27
    6.2%
    13
    5.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Endovascular Therapy, IV Rt-PA Alone
    Comments Test of null hypothesis (equal proportions of subjects with sICH within 30 hours post IV tPA initiation in IV Only and Endovascular treatment arms) versus alternative hypothesis (unequal proportions of subjects with sICH within 30 hours post IV tPA initiation in IV Only and Endovascular treatment arms).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value .8275
    Comments The CMH statistic is tested at the two-sided alpha level of 0.01.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel (CMH) test adjusting for the dichotomized baseline NIHSS score (<20 or ≥20).
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value .4
    Confidence Interval (2-Sided) 99%
    -4.6 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Positive adjusted risk difference indicates greater risk in the Endovascular group, while negative adjusted risk difference indicates greater risk in the IV Only group.
    4. Secondary Outcome
    Title Incidence of Parenchymal Type II (PH2) Hematomas
    Description 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.
    Time Frame within 30 hours post IV rt-PA

    Outcome Measure Data

    Analysis Population Description
    Subjects were excluded if a post-baseline CT scan was not obtained within 30 hours of randomization (i.e., participants who died, had care withdrawn at the request of the family, or underwent imaging after the 30-hour window).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 417 207
    Number [participants]
    25
    5.8%
    13
    5.9%
    5. Secondary Outcome
    Title Asymptomatic Intracranial Hemorrhage
    Description 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.
    Time Frame within 30 hours post IV rt-PA

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned.
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    Number [participants]
    119
    27.4%
    42
    18.9%
    6. Secondary Outcome
    Title National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater.
    Description 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.
    Time Frame at 24 hours post randomization

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned. Subjects with missing NIHSS and NIHSS measured <18 hours or >30 hours post-randomization are assigned an unfavorable outcome (NIHSS score>1).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    NIHSS 0-1
    44
    10.1%
    22
    9.9%
    NIHSS 2+
    390
    89.9%
    200
    90.1%
    7. Secondary Outcome
    Title National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater.
    Description 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.
    Time Frame at 90 days post randomization

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned. Subjects with missing NIHSS and NIHSS measured <60 days or >120 days post-randomization are assigned an unfavorable outcome (NIHSS score>1).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    NIHSSS 0-1
    120
    27.6%
    50
    22.5%
    NIHSSS 2+
    314
    72.4%
    172
    77.5%
    8. Secondary Outcome
    Title Barthel Index (BI) Dichotomized 0-90 Versus 95-100
    Description 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.
    Time Frame at 90 days post randomization

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned. Subjects with missing BI and BI measured <60 days or >120 days post-randomization are assigned an unfavorable outcome (BI 0-90).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    BI 95-100
    183
    42.2%
    86
    38.7%
    BI 0-90
    251
    57.8%
    136
    61.3%
    9. Secondary Outcome
    Title Trail Making Test Part A Time
    Description 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.
    Time Frame 90 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Participants were excluded if the Trail Making Test was not assessed or if they failed to complete Part A.
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 244 127
    Mean (Standard Deviation) [seconds]
    84.2
    (64.3)
    82.0
    (62.3)
    10. Secondary Outcome
    Title Trail Making Test Part B Time
    Description 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.
    Time Frame at 90 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Participants were excluded if the Trail Making Test was not assessed or if they failed to complete Part B.
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 183 92
    Mean (Standard Deviation) [seconds]
    143.8
    (75.3)
    141.3
    (78.4)
    11. Secondary Outcome
    Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
    Description 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.
    Time Frame at 180 days

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned. Subjects with missing mRS and mRS measured <150 days or >210 days post-randomization are assigned an unfavorable outcome (mRS>2).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    mRS 0-2
    179
    41.2%
    86
    38.7%
    mRS 3-6
    255
    58.8%
    136
    61.3%
    12. Secondary Outcome
    Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
    Description 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.
    Time Frame 270 days

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned. Subjects with missing mRS and mRS measured <240 days or >300 days post-randomization are assigned an unfavorable outcome (mRS>2).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    mRS 0-2
    177
    40.8%
    88
    39.6%
    mRS 3-6
    257
    59.2%
    134
    60.4%
    13. Secondary Outcome
    Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
    Description 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.
    Time Frame 360 days post randomization

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat analysis sample includes all subjects who are randomized, and each subject is analyzed according to the treatment group to which they were randomly assigned. Subjects with missing mRS and mRS measured <330 days or >390 days post-randomization are assigned an unfavorable outcome (mRS>2).
    Arm/Group Title Endovascular Therapy IV Rt-PA Alone
    Arm/Group Description 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. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    Measure Participants 434 222
    mRS 0-2
    191
    44%
    95
    42.8%
    mRS 3-6
    243
    56%
    127
    57.2%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Endovascular IV Only
    Arm/Group Description Group two will receive a lower dose or a standard dose of IV rt-PA and then undergo an angiogram test (cerebral angiography) rightafter the medicine is given to check for blood clots. If a clot is not seenthen no more treatment will be given. If a clot is seen, theneurointerventionalist will then choose (based on the location andextent of the blood clot) a protocol approved endovascular treatmentgiven directly in the brain artery that will be most effective inreopening the blocked artery. Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
    All Cause Mortality
    Endovascular IV Only
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Endovascular IV Only
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 256/434 (59%) 126/222 (56.8%)
    Blood and lymphatic system disorders
    Anaemia 4/434 (0.9%) 4 4/222 (1.8%) 4
    Coagulopathy 0/434 (0%) 0 1/222 (0.5%) 1
    Disseminated intravascular coagulation 0/434 (0%) 0 1/222 (0.5%) 1
    Hypoprothrombinaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Iron deficiency anaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Thrombocytopenia 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 2/434 (0.5%) 2 1/222 (0.5%) 1
    Angina pectoris 0/434 (0%) 0 1/222 (0.5%) 1
    Atrial fibrillation 7/434 (1.6%) 8 5/222 (2.3%) 5
    Atrial flutter 3/434 (0.7%) 3 0/222 (0%) 0
    Atrial tachycardia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cardiac arrest 8/434 (1.8%) 9 4/222 (1.8%) 4
    Cardiac failure 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cardiac failure acute 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cardiac failure congestive 4/434 (0.9%) 4 4/222 (1.8%) 4
    Cardiac valve vegetation 1/434 (0.2%) 1 0/222 (0%) 0
    Cardio-respiratory arrest 1/434 (0.2%) 1 2/222 (0.9%) 2
    Cardiogenic shock 2/434 (0.5%) 2 0/222 (0%) 0
    Cardiomyopathy 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiopulmonary failure 1/434 (0.2%) 1 0/222 (0%) 0
    Coronary artery disease 1/434 (0.2%) 1 0/222 (0%) 0
    Electromechanical dissociation 1/434 (0.2%) 1 0/222 (0%) 0
    Endocarditis noninfective 1/434 (0.2%) 1 0/222 (0%) 0
    Intracardiac thrombus 1/434 (0.2%) 1 1/222 (0.5%) 1
    Ischaemic cardiomyopathy 0/434 (0%) 0 1/222 (0.5%) 1
    Mitral valve disease 2/434 (0.5%) 2 0/222 (0%) 0
    Mitral valve stenosis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Myocardial infarction 4/434 (0.9%) 4 0/222 (0%) 0
    Pericardial effusion 1/434 (0.2%) 1 0/222 (0%) 0
    Pericardial haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Sick sinus syndrome 3/434 (0.7%) 3 0/222 (0%) 0
    Sinus bradycardia 1/434 (0.2%) 1 0/222 (0%) 0
    Tachyarrhythmia 0/434 (0%) 0 1/222 (0.5%) 1
    Tachycardia 1/434 (0.2%) 1 0/222 (0%) 0
    Ventricular tachycardia 2/434 (0.5%) 2 4/222 (1.8%) 4
    Congenital, familial and genetic disorders
    Atrial septal defect 4/434 (0.9%) 4 1/222 (0.5%) 1
    Hereditary cerebral degeneration 0/434 (0%) 0 1/222 (0.5%) 1
    Eye disorders
    Diplopia 1/434 (0.2%) 1 0/222 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/434 (0.2%) 1 0/222 (0%) 0
    Colitis 2/434 (0.5%) 2 0/222 (0%) 0
    Diarrhoea 1/434 (0.2%) 1 0/222 (0%) 0
    Gastritis 1/434 (0.2%) 1 0/222 (0%) 0
    Gastrointestinal haemorrhage 2/434 (0.5%) 2 3/222 (1.4%) 3
    Gastrooesophageal reflux disease 1/434 (0.2%) 1 0/222 (0%) 0
    Gingival bleeding 0/434 (0%) 0 1/222 (0.5%) 1
    Haematemesis 1/434 (0.2%) 1 0/222 (0%) 0
    Haematochezia 1/434 (0.2%) 1 0/222 (0%) 0
    Ileus 1/434 (0.2%) 1 0/222 (0%) 0
    Intestinal obstruction 1/434 (0.2%) 1 0/222 (0%) 0
    Pancreatic mass 1/434 (0.2%) 1 0/222 (0%) 0
    Pancreatitis 1/434 (0.2%) 1 0/222 (0%) 0
    Peritonitis 1/434 (0.2%) 1 0/222 (0%) 0
    Retroperitoneal haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Retroperitoneal haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Small intestinal obstruction 0/434 (0%) 0 1/222 (0.5%) 1
    Umbilical hernia 1/434 (0.2%) 1 0/222 (0%) 0
    General disorders
    Brain death 1/434 (0.2%) 1 0/222 (0%) 0
    Chest discomfort 3/434 (0.7%) 4 0/222 (0%) 0
    Chest pain 3/434 (0.7%) 3 1/222 (0.5%) 1
    Extravasation 1/434 (0.2%) 1 0/222 (0%) 0
    General physical health deterioration 0/434 (0%) 0 1/222 (0.5%) 1
    Multi-organ failure 2/434 (0.5%) 2 0/222 (0%) 0
    Non-cardiac chest pain 1/434 (0.2%) 1 0/222 (0%) 0
    Oedema due to cardiac disease 0/434 (0%) 0 1/222 (0.5%) 1
    Oedema peripheral 1/434 (0.2%) 1 0/222 (0%) 0
    Pyrexia 0/434 (0%) 0 1/222 (0.5%) 1
    Systemic inflammatory response syndrome 0/434 (0%) 0 2/222 (0.9%) 2
    Vessel puncture site haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Vessel puncture site haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/434 (0.2%) 1 0/222 (0%) 0
    Immune system disorders
    Anaphylactic reaction 1/434 (0.2%) 1 0/222 (0%) 0
    Infections and infestations
    Abdominal wall infection 0/434 (0%) 0 1/222 (0.5%) 1
    Appendicitis 1/434 (0.2%) 1 0/222 (0%) 0
    Bacteraemia 0/434 (0%) 0 1/222 (0.5%) 1
    Bacteriuria 1/434 (0.2%) 1 0/222 (0%) 0
    Cellulitis 2/434 (0.5%) 2 0/222 (0%) 0
    Clostridium difficile colitis 1/434 (0.2%) 1 0/222 (0%) 0
    Endocarditis 0/434 (0%) 0 1/222 (0.5%) 1
    Endocarditis bacterial 1/434 (0.2%) 1 0/222 (0%) 0
    Gangrene 1/434 (0.2%) 1 0/222 (0%) 0
    Gastroenteritis 1/434 (0.2%) 1 2/222 (0.9%) 2
    Haematoma infection 1/434 (0.2%) 1 0/222 (0%) 0
    Infected skin ulcer 1/434 (0.2%) 1 0/222 (0%) 0
    Infection 0/434 (0%) 0 1/222 (0.5%) 1
    Lobar pneumonia 0/434 (0%) 0 1/222 (0.5%) 1
    Lung infection pseudomonal 1/434 (0.2%) 1 0/222 (0%) 0
    Pneumonia 16/434 (3.7%) 17 8/222 (3.6%) 8
    Pneumonia primary atypical 0/434 (0%) 0 1/222 (0.5%) 1
    Postoperative wound infection 1/434 (0.2%) 1 1/222 (0.5%) 1
    Pulmonary sepsis 0/434 (0%) 0 2/222 (0.9%) 2
    Respiratory tract infection 3/434 (0.7%) 3 0/222 (0%) 0
    Sepsis 6/434 (1.4%) 6 5/222 (2.3%) 5
    Sepsis syndrome 1/434 (0.2%) 1 0/222 (0%) 0
    Septic shock 1/434 (0.2%) 1 2/222 (0.9%) 2
    Urinary tract infection 8/434 (1.8%) 11 7/222 (3.2%) 7
    Urosepsis 2/434 (0.5%) 2 2/222 (0.9%) 2
    Wound infection 0/434 (0%) 0 1/222 (0.5%) 1
    Injury, poisoning and procedural complications
    Aortic injury 1/434 (0.2%) 1 0/222 (0%) 0
    Arterial injury 1/434 (0.2%) 1 0/222 (0%) 0
    Brain herniation 7/434 (1.6%) 7 2/222 (0.9%) 3
    Cardiac procedure complication 1/434 (0.2%) 1 0/222 (0%) 0
    Cervical vertebral fracture 1/434 (0.2%) 1 0/222 (0%) 0
    Concussion 1/434 (0.2%) 1 0/222 (0%) 0
    Difficult to wean from ventilator 1/434 (0.2%) 1 0/222 (0%) 0
    Drug dispensing error 0/434 (0%) 0 1/222 (0.5%) 1
    Fall 1/434 (0.2%) 1 1/222 (0.5%) 1
    Feeding tube complication 1/434 (0.2%) 1 0/222 (0%) 0
    Femoral neck fracture 1/434 (0.2%) 1 0/222 (0%) 0
    Femur fracture 1/434 (0.2%) 1 0/222 (0%) 0
    Head injury 0/434 (0%) 0 1/222 (0.5%) 1
    Hip fracture 1/434 (0.2%) 1 0/222 (0%) 0
    Injury 1/434 (0.2%) 1 0/222 (0%) 0
    Medication error 0/434 (0%) 0 1/222 (0.5%) 1
    Post procedural haematoma 0/434 (0%) 0 1/222 (0.5%) 1
    Rib fracture 0/434 (0%) 0 1/222 (0.5%) 1
    Stent occlusion 0/434 (0%) 0 1/222 (0.5%) 1
    Subdural haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Thermal burn 1/434 (0.2%) 1 0/222 (0%) 0
    Thrombosis in device 1/434 (0.2%) 1 0/222 (0%) 0
    Vascular injury 1/434 (0.2%) 1 0/222 (0%) 0
    Vascular procedure complication 1/434 (0.2%) 1 0/222 (0%) 0
    Ventriculoperitoneal shunt malfunction 1/434 (0.2%) 1 0/222 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 1/434 (0.2%) 1 0/222 (0%) 0
    Blood culture positive 1/434 (0.2%) 1 0/222 (0%) 0
    Blood glucose increased 1/434 (0.2%) 1 0/222 (0%) 0
    Blood magnesium decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Blood osmolarity decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Blood phosphorus decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Computerised tomogram abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Electrocardiogram ST segment abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Electroencephalogram abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Haematocrit decreased 1/434 (0.2%) 1 0/222 (0%) 0
    NIH stroke scale score increased 1/434 (0.2%) 1 0/222 (0%) 0
    Oxygen saturation decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Troponin increased 1/434 (0.2%) 1 0/222 (0%) 0
    Weight decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Metabolism and nutrition disorders
    Acid-base balance disorder mixed 0/434 (0%) 0 1/222 (0.5%) 1
    Anorexia 1/434 (0.2%) 1 0/222 (0%) 0
    Dehydration 2/434 (0.5%) 2 1/222 (0.5%) 1
    Diabetes mellitus insulin-dependent 0/434 (0%) 0 1/222 (0.5%) 1
    Failure to thrive 1/434 (0.2%) 1 1/222 (0.5%) 1
    Hyperglycaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Hypokalaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/434 (0.2%) 1 0/222 (0%) 0
    Muscular weakness 1/434 (0.2%) 1 1/222 (0.5%) 1
    Osteoarthritis 0/434 (0%) 0 1/222 (0.5%) 1
    Pain in extremity 1/434 (0.2%) 1 0/222 (0%) 0
    Pain in jaw 1/434 (0.2%) 1 0/222 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioblastoma 1/434 (0.2%) 1 0/222 (0%) 0
    Gliomatosis cerebri 1/434 (0.2%) 1 0/222 (0%) 0
    Lung adenocarcinoma 0/434 (0%) 0 1/222 (0.5%) 1
    Lung neoplasm malignant 1/434 (0.2%) 1 1/222 (0.5%) 1
    Metastatic neoplasm 1/434 (0.2%) 1 0/222 (0%) 0
    Prostate cancer 1/434 (0.2%) 1 0/222 (0%) 0
    Nervous system disorders
    Aphasia 1/434 (0.2%) 1 0/222 (0%) 0
    Brain compression 1/434 (0.2%) 1 0/222 (0%) 0
    Brain oedema 46/434 (10.6%) 46 19/222 (8.6%) 20
    Brain stem infarction 1/434 (0.2%) 1 0/222 (0%) 0
    Carotid artery dissection 3/434 (0.7%) 3 0/222 (0%) 0
    Carotid artery occlusion 1/434 (0.2%) 1 0/222 (0%) 0
    Carotid artery stenosis 0/434 (0%) 0 2/222 (0.9%) 2
    Cerebellar haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Cerebellar infarction 2/434 (0.5%) 2 0/222 (0%) 0
    Cerebral haematoma 0/434 (0%) 0 1/222 (0.5%) 1
    Cerebral haemorrhage 8/434 (1.8%) 8 8/222 (3.6%) 8
    Cerebral infarction 9/434 (2.1%) 9 1/222 (0.5%) 1
    Cerebrovascular accident 18/434 (4.1%) 19 12/222 (5.4%) 12
    Cerebrovascular disorder 0/434 (0%) 0 1/222 (0.5%) 1
    Coma 1/434 (0.2%) 1 0/222 (0%) 0
    Complex partial seizures 1/434 (0.2%) 1 0/222 (0%) 0
    Convulsion 9/434 (2.1%) 9 9/222 (4.1%) 9
    Depressed level of consciousness 1/434 (0.2%) 1 2/222 (0.9%) 2
    Dizziness 1/434 (0.2%) 1 0/222 (0%) 0
    Encephalopathy 1/434 (0.2%) 1 1/222 (0.5%) 1
    Facial spasm 1/434 (0.2%) 1 0/222 (0%) 0
    Haemorrhage intracranial 12/434 (2.8%) 12 8/222 (3.6%) 8
    Haemorrhagic cerebral infarction 1/434 (0.2%) 1 0/222 (0%) 0
    Haemorrhagic stroke 1/434 (0.2%) 1 0/222 (0%) 0
    Haemorrhagic transformation stroke 6/434 (1.4%) 6 6/222 (2.7%) 6
    Headache 1/434 (0.2%) 1 0/222 (0%) 0
    Hemiparesis 2/434 (0.5%) 2 0/222 (0%) 0
    Hydrocephalus 1/434 (0.2%) 1 0/222 (0%) 0
    Intracranial haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Intracranial pressure increased 1/434 (0.2%) 1 1/222 (0.5%) 1
    Intraventricular haemorrhage 2/434 (0.5%) 2 0/222 (0%) 0
    Ischaemic stroke 6/434 (1.4%) 7 2/222 (0.9%) 2
    Lethargy 0/434 (0%) 0 3/222 (1.4%) 3
    Mental impairment 0/434 (0%) 0 1/222 (0.5%) 1
    Migraine 1/434 (0.2%) 1 1/222 (0.5%) 1
    Neurological symptom 12/434 (2.8%) 13 4/222 (1.8%) 4
    Presyncope 0/434 (0%) 0 1/222 (0.5%) 1
    Status epilepticus 1/434 (0.2%) 2 0/222 (0%) 0
    Stroke in evolution 0/434 (0%) 0 2/222 (0.9%) 2
    Subarachnoid haemorrhage 6/434 (1.4%) 6 0/222 (0%) 0
    Syncope 1/434 (0.2%) 1 1/222 (0.5%) 1
    Thalamic infarction 1/434 (0.2%) 1 0/222 (0%) 0
    Transient ischaemic attack 3/434 (0.7%) 3 2/222 (0.9%) 2
    Tremor 0/434 (0%) 0 1/222 (0.5%) 1
    Psychiatric disorders
    Aggression 1/434 (0.2%) 1 0/222 (0%) 0
    Agitation 1/434 (0.2%) 1 0/222 (0%) 0
    Anxiety 0/434 (0%) 0 1/222 (0.5%) 1
    Confusional state 1/434 (0.2%) 2 0/222 (0%) 0
    Delirium tremens 0/434 (0%) 0 1/222 (0.5%) 1
    Depression 0/434 (0%) 0 2/222 (0.9%) 2
    Emotional disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Mental status changes 6/434 (1.4%) 7 2/222 (0.9%) 2
    Suicide attempt 1/434 (0.2%) 1 0/222 (0%) 0
    Renal and urinary disorders
    Haematuria 2/434 (0.5%) 2 0/222 (0%) 0
    Nephrolithiasis 1/434 (0.2%) 1 0/222 (0%) 0
    Renal failure 1/434 (0.2%) 1 1/222 (0.5%) 1
    Renal failure acute 1/434 (0.2%) 1 0/222 (0%) 0
    Renal failure chronic 1/434 (0.2%) 1 0/222 (0%) 0
    Renal mass 0/434 (0%) 0 1/222 (0.5%) 1
    Urinary retention 1/434 (0.2%) 1 1/222 (0.5%) 1
    Reproductive system and breast disorders
    Pelvic pain 1/434 (0.2%) 1 0/222 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 3/434 (0.7%) 3 1/222 (0.5%) 2
    Acute respiratory distress syndrome 2/434 (0.5%) 2 0/222 (0%) 0
    Acute respiratory failure 3/434 (0.7%) 3 1/222 (0.5%) 1
    Apnoea 1/434 (0.2%) 1 1/222 (0.5%) 1
    Aspiration 0/434 (0%) 0 1/222 (0.5%) 1
    Atelectasis 1/434 (0.2%) 1 2/222 (0.9%) 2
    Dyspnoea 3/434 (0.7%) 3 1/222 (0.5%) 1
    Epistaxis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Haemoptysis 0/434 (0%) 0 1/222 (0.5%) 1
    Hypoxia 5/434 (1.2%) 5 0/222 (0%) 0
    Lung infiltration 1/434 (0.2%) 1 0/222 (0%) 0
    Obstructive airways disorder 0/434 (0%) 0 1/222 (0.5%) 1
    Pneumonia aspiration 6/434 (1.4%) 6 2/222 (0.9%) 2
    Pneumothorax 0/434 (0%) 0 1/222 (0.5%) 1
    Pulmonary embolism 4/434 (0.9%) 4 8/222 (3.6%) 8
    Pulmonary haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Pulmonary oedema 2/434 (0.5%) 2 1/222 (0.5%) 1
    Respiratory arrest 1/434 (0.2%) 1 2/222 (0.9%) 2
    Respiratory distress 5/434 (1.2%) 5 4/222 (1.8%) 4
    Respiratory failure 18/434 (4.1%) 18 5/222 (2.3%) 5
    Skin and subcutaneous tissue disorders
    Angioneurotic oedema 0/434 (0%) 0 1/222 (0.5%) 1
    Decubitus ulcer 1/434 (0.2%) 1 0/222 (0%) 0
    Skin ulcer 1/434 (0.2%) 1 0/222 (0%) 0
    Surgical and medical procedures
    Aortic valve replacement 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiac pacemaker insertion 0/434 (0%) 0 1/222 (0.5%) 1
    Cardiac pacemaker replacement 1/434 (0.2%) 1 0/222 (0%) 0
    Carotid endarterectomy 2/434 (0.5%) 2 2/222 (0.9%) 3
    Cholecystectomy 1/434 (0.2%) 1 0/222 (0%) 0
    Craniectomy 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cranioplasty 9/434 (2.1%) 9 3/222 (1.4%) 3
    Intubation 0/434 (0%) 0 1/222 (0.5%) 2
    Medical device implantation 1/434 (0.2%) 1 0/222 (0%) 0
    Mitral valve replacement 0/434 (0%) 0 1/222 (0.5%) 1
    Nephrectomy 0/434 (0%) 0 1/222 (0.5%) 1
    Surgery 2/434 (0.5%) 2 0/222 (0%) 0
    Tracheostomy 2/434 (0.5%) 2 1/222 (0.5%) 1
    Vascular disorders
    Aortic arteriosclerosis 1/434 (0.2%) 1 0/222 (0%) 0
    Aortic stenosis 0/434 (0%) 0 1/222 (0.5%) 1
    Arterial restenosis 1/434 (0.2%) 1 0/222 (0%) 0
    Arterial thrombosis limb 1/434 (0.2%) 1 0/222 (0%) 0
    Deep vein thrombosis 7/434 (1.6%) 7 2/222 (0.9%) 2
    Femoral artery occlusion 0/434 (0%) 0 1/222 (0.5%) 1
    Haematoma 1/434 (0.2%) 1 1/222 (0.5%) 1
    Haemodynamic instability 1/434 (0.2%) 1 0/222 (0%) 0
    Haemorrhage 2/434 (0.5%) 2 0/222 (0%) 0
    Hypertension 4/434 (0.9%) 4 2/222 (0.9%) 2
    Hypertensive crisis 1/434 (0.2%) 1 0/222 (0%) 0
    Hypertensive emergency 0/434 (0%) 0 1/222 (0.5%) 1
    Hypotension 6/434 (1.4%) 6 6/222 (2.7%) 6
    Iliac artery thrombosis 1/434 (0.2%) 1 0/222 (0%) 0
    Peripheral arterial occlusive disease 1/434 (0.2%) 1 0/222 (0%) 0
    Peripheral artery aneurysm 1/434 (0.2%) 1 0/222 (0%) 0
    Peripheral embolism 1/434 (0.2%) 1 0/222 (0%) 0
    Peripheral ischaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Peripheral vascular disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Shock 1/434 (0.2%) 1 0/222 (0%) 0
    Thrombophlebitis 0/434 (0%) 0 1/222 (0.5%) 1
    Other (Not Including Serious) Adverse Events
    Endovascular IV Only
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 385/434 (88.7%) 202/222 (91%)
    Blood and lymphatic system disorders
    Anaemia 39/434 (9%) 41 16/222 (7.2%) 17
    Coagulopathy 2/434 (0.5%) 2 0/222 (0%) 0
    Haemorrhagic disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Hilar lymphadenopathy 1/434 (0.2%) 1 0/222 (0%) 0
    Iron deficiency anaemia 2/434 (0.5%) 2 1/222 (0.5%) 1
    Leukocytosis 7/434 (1.6%) 7 5/222 (2.3%) 5
    Lymphadenopathy 2/434 (0.5%) 2 0/222 (0%) 0
    Lymphadenopathy mediastinal 1/434 (0.2%) 1 0/222 (0%) 0
    Pernicious anaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Splenic infarction 1/434 (0.2%) 1 0/222 (0%) 0
    Thrombocytopenia 5/434 (1.2%) 5 5/222 (2.3%) 5
    Cardiac disorders
    Acute myocardial infarction 4/434 (0.9%) 4 0/222 (0%) 0
    Angina pectoris 1/434 (0.2%) 1 0/222 (0%) 0
    Aortic valve disease 1/434 (0.2%) 1 0/222 (0%) 0
    Aortic valve stenosis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Arrhythmia 4/434 (0.9%) 4 1/222 (0.5%) 1
    Arrhythmia supraventricular 1/434 (0.2%) 1 0/222 (0%) 0
    Atrial fibrillation 37/434 (8.5%) 41 21/222 (9.5%) 22
    Atrial flutter 3/434 (0.7%) 4 1/222 (0.5%) 1
    Atrioventricular block 1/434 (0.2%) 1 0/222 (0%) 0
    Bradycardia 18/434 (4.1%) 19 9/222 (4.1%) 9
    Bundle branch block right 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiac disorder 0/434 (0%) 0 1/222 (0.5%) 1
    Cardiac failure 2/434 (0.5%) 2 0/222 (0%) 0
    Cardiac failure acute 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiac failure congestive 16/434 (3.7%) 17 7/222 (3.2%) 8
    Cardiac valve disease 2/434 (0.5%) 2 0/222 (0%) 0
    Cardiac valve vegetation 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiogenic shock 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiomegaly 2/434 (0.5%) 2 2/222 (0.9%) 2
    Cardiomyopathy 1/434 (0.2%) 1 2/222 (0.9%) 2
    Cardiovascular disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Coronary artery disease 1/434 (0.2%) 1 0/222 (0%) 0
    Diastolic dysfunction 1/434 (0.2%) 1 1/222 (0.5%) 1
    Intracardiac thrombus 1/434 (0.2%) 1 0/222 (0%) 0
    Ischaemic cardiomyopathy 1/434 (0.2%) 1 0/222 (0%) 0
    Mitral valve stenosis 1/434 (0.2%) 1 0/222 (0%) 0
    Myocardial infarction 2/434 (0.5%) 2 0/222 (0%) 0
    Myocardial ischaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Nodal arrhythmia 1/434 (0.2%) 1 0/222 (0%) 0
    Palpitations 1/434 (0.2%) 1 1/222 (0.5%) 1
    Sick sinus syndrome 1/434 (0.2%) 1 0/222 (0%) 0
    Sinus arrhythmia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Sinus bradycardia 2/434 (0.5%) 2 7/222 (3.2%) 7
    Sinus tachycardia 4/434 (0.9%) 4 1/222 (0.5%) 1
    Supraventricular tachycardia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Tachycardia 15/434 (3.5%) 16 9/222 (4.1%) 9
    Ventricular arrhythmia 0/434 (0%) 0 1/222 (0.5%) 1
    Ventricular extrasystoles 4/434 (0.9%) 4 1/222 (0.5%) 1
    Ventricular tachycardia 6/434 (1.4%) 6 3/222 (1.4%) 3
    Congenital, familial and genetic disorders
    Atrial septal defect 3/434 (0.7%) 3 2/222 (0.9%) 2
    Congenital cystic kidney disease 1/434 (0.2%) 1 0/222 (0%) 0
    Homocystinaemia 0/434 (0%) 0 1/222 (0.5%) 1
    Ear and labyrinth disorders
    Cerumen impaction 2/434 (0.5%) 2 0/222 (0%) 0
    Deafness 0/434 (0%) 0 1/222 (0.5%) 1
    Ear pain 1/434 (0.2%) 1 0/222 (0%) 0
    Vertigo 1/434 (0.2%) 1 0/222 (0%) 0
    Endocrine disorders
    Diabetes insipidus 1/434 (0.2%) 1 0/222 (0%) 0
    Hypothyroidism 1/434 (0.2%) 1 3/222 (1.4%) 3
    Eye disorders
    Conjunctival haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Conjunctivitis 2/434 (0.5%) 2 1/222 (0.5%) 1
    Dry eye 2/434 (0.5%) 2 0/222 (0%) 0
    Eye disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Eye pain 1/434 (0.2%) 2 2/222 (0.9%) 2
    Eye swelling 0/434 (0%) 0 1/222 (0.5%) 1
    Eyelid oedema 0/434 (0%) 0 1/222 (0.5%) 1
    Eyelid ptosis 2/434 (0.5%) 3 0/222 (0%) 0
    Ocular hyperaemia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Pupil fixed 0/434 (0%) 0 1/222 (0.5%) 1
    Scleral oedema 2/434 (0.5%) 2 1/222 (0.5%) 1
    Ulcerative keratitis 1/434 (0.2%) 1 0/222 (0%) 0
    Vision blurred 2/434 (0.5%) 2 0/222 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 1/434 (0.2%) 1 0/222 (0%) 0
    Abdominal distension 2/434 (0.5%) 2 0/222 (0%) 0
    Abdominal pain 8/434 (1.8%) 8 2/222 (0.9%) 2
    Abdominal pain upper 3/434 (0.7%) 3 1/222 (0.5%) 1
    Abnormal faeces 1/434 (0.2%) 1 1/222 (0.5%) 1
    Anal haemorrhage 0/434 (0%) 0 1/222 (0.5%) 1
    Ascites 1/434 (0.2%) 1 1/222 (0.5%) 1
    Bowel movement irregularity 1/434 (0.2%) 1 0/222 (0%) 0
    Constipation 41/434 (9.4%) 43 26/222 (11.7%) 27
    Diarrhoea 21/434 (4.8%) 21 9/222 (4.1%) 9
    Dyspepsia 8/434 (1.8%) 8 4/222 (1.8%) 4
    Dysphagia 14/434 (3.2%) 14 3/222 (1.4%) 3
    Faecal incontinence 3/434 (0.7%) 3 0/222 (0%) 0
    Flatulence 1/434 (0.2%) 1 1/222 (0.5%) 1
    Food poisoning 0/434 (0%) 0 1/222 (0.5%) 1
    Gastritis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Gastritis haemorrhagic 1/434 (0.2%) 1 0/222 (0%) 0
    Gastrointestinal haemorrhage 5/434 (1.2%) 5 3/222 (1.4%) 3
    Gastrooesophageal reflux disease 6/434 (1.4%) 6 2/222 (0.9%) 2
    Gingival bleeding 3/434 (0.7%) 3 6/222 (2.7%) 6
    Gingivitis 1/434 (0.2%) 1 0/222 (0%) 0
    Haematemesis 4/434 (0.9%) 4 2/222 (0.9%) 2
    Haematochezia 3/434 (0.7%) 3 1/222 (0.5%) 1
    Haemorrhoids 5/434 (1.2%) 5 1/222 (0.5%) 1
    Hiatus hernia 1/434 (0.2%) 1 0/222 (0%) 0
    Hypoaesthesia oral 0/434 (0%) 0 1/222 (0.5%) 1
    Ileus 2/434 (0.5%) 2 1/222 (0.5%) 1
    Impaired gastric emptying 1/434 (0.2%) 1 2/222 (0.9%) 2
    Inguinal hernia 1/434 (0.2%) 1 0/222 (0%) 0
    Loose tooth 0/434 (0%) 0 1/222 (0.5%) 1
    Melaena 1/434 (0.2%) 1 0/222 (0%) 0
    Mouth haemorrhage 3/434 (0.7%) 3 1/222 (0.5%) 1
    Nausea 43/434 (9.9%) 45 17/222 (7.7%) 18
    Oesophageal stenosis 1/434 (0.2%) 1 0/222 (0%) 0
    Periproctitis 0/434 (0%) 0 1/222 (0.5%) 1
    Rectal haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Retroperitoneal haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Salivary hypersecretion 1/434 (0.2%) 1 0/222 (0%) 0
    Stomach discomfort 2/434 (0.5%) 2 0/222 (0%) 0
    Swollen tongue 2/434 (0.5%) 2 0/222 (0%) 0
    Tongue haemorrhage 1/434 (0.2%) 1 2/222 (0.9%) 2
    Tongue ulceration 1/434 (0.2%) 1 0/222 (0%) 0
    Toothache 2/434 (0.5%) 2 1/222 (0.5%) 1
    Vomiting 39/434 (9%) 40 21/222 (9.5%) 22
    General disorders
    Adverse drug reaction 2/434 (0.5%) 2 0/222 (0%) 0
    Asthenia 2/434 (0.5%) 2 0/222 (0%) 0
    Catheter site bruise 1/434 (0.2%) 1 0/222 (0%) 0
    Catheter site haemorrhage 3/434 (0.7%) 3 0/222 (0%) 0
    Catheter site related reaction 0/434 (0%) 0 1/222 (0.5%) 1
    Chest discomfort 1/434 (0.2%) 1 2/222 (0.9%) 2
    Chest pain 17/434 (3.9%) 17 9/222 (4.1%) 10
    Chills 1/434 (0.2%) 1 1/222 (0.5%) 1
    Discomfort 4/434 (0.9%) 4 1/222 (0.5%) 1
    Extravasation 0/434 (0%) 0 1/222 (0.5%) 1
    Face oedema 2/434 (0.5%) 2 0/222 (0%) 0
    Facial pain 0/434 (0%) 0 1/222 (0.5%) 1
    Fatigue 10/434 (2.3%) 10 2/222 (0.9%) 2
    Feeling cold 1/434 (0.2%) 1 0/222 (0%) 0
    Generalised oedema 4/434 (0.9%) 4 3/222 (1.4%) 3
    Hyperthermia 0/434 (0%) 0 2/222 (0.9%) 2
    Implant site pain 0/434 (0%) 0 1/222 (0.5%) 1
    Infusion site erythema 1/434 (0.2%) 2 0/222 (0%) 0
    Infusion site haemorrhage 4/434 (0.9%) 4 3/222 (1.4%) 3
    Infusion site oedema 1/434 (0.2%) 1 0/222 (0%) 0
    Injection site extravasation 1/434 (0.2%) 1 0/222 (0%) 0
    Local swelling 1/434 (0.2%) 1 0/222 (0%) 0
    Malaise 1/434 (0.2%) 1 0/222 (0%) 0
    Mass 1/434 (0.2%) 1 0/222 (0%) 0
    Non-cardiac chest pain 1/434 (0.2%) 1 0/222 (0%) 0
    Oedema peripheral 23/434 (5.3%) 29 13/222 (5.9%) 15
    Pain 30/434 (6.9%) 32 14/222 (6.3%) 16
    Pitting oedema 0/434 (0%) 0 1/222 (0.5%) 1
    Puncture site haemorrhage 3/434 (0.7%) 3 0/222 (0%) 0
    Pyrexia 35/434 (8.1%) 36 31/222 (14%) 32
    Swelling 1/434 (0.2%) 1 0/222 (0%) 0
    Systemic inflammatory response syndrome 0/434 (0%) 0 1/222 (0.5%) 1
    Vessel puncture site bruise 1/434 (0.2%) 1 1/222 (0.5%) 1
    Vessel puncture site haematoma 15/434 (3.5%) 15 1/222 (0.5%) 1
    Vessel puncture site haemorrhage 2/434 (0.5%) 2 1/222 (0.5%) 1
    Hepatobiliary disorders
    Cholecystitis acute 1/434 (0.2%) 1 0/222 (0%) 0
    Hepatomegaly 1/434 (0.2%) 1 0/222 (0%) 0
    Immune system disorders
    Drug hypersensitivity 1/434 (0.2%) 1 0/222 (0%) 0
    Hypersensitivity 1/434 (0.2%) 1 0/222 (0%) 0
    Infections and infestations
    Abdominal wall abscess 1/434 (0.2%) 1 0/222 (0%) 0
    Abscess limb 0/434 (0%) 0 1/222 (0.5%) 1
    Bacteraemia 3/434 (0.7%) 3 0/222 (0%) 0
    Bronchitis 4/434 (0.9%) 4 4/222 (1.8%) 4
    Bronchitis acute 1/434 (0.2%) 1 0/222 (0%) 0
    Candidiasis 4/434 (0.9%) 4 1/222 (0.5%) 1
    Cellulitis 3/434 (0.7%) 3 1/222 (0.5%) 1
    Chest wall abscess 1/434 (0.2%) 1 0/222 (0%) 0
    Clostridial infection 4/434 (0.9%) 4 3/222 (1.4%) 3
    Clostridium difficile colitis 2/434 (0.5%) 2 1/222 (0.5%) 1
    Cystitis 1/434 (0.2%) 1 0/222 (0%) 0
    Diarrhoea infectious 0/434 (0%) 0 1/222 (0.5%) 1
    Enterococcal infection 0/434 (0%) 0 1/222 (0.5%) 1
    Eye infection 2/434 (0.5%) 2 2/222 (0.9%) 2
    Fungal infection 5/434 (1.2%) 5 1/222 (0.5%) 1
    Fungal skin infection 2/434 (0.5%) 2 0/222 (0%) 0
    Gastroenteritis 1/434 (0.2%) 1 0/222 (0%) 0
    Herpes simplex 1/434 (0.2%) 1 0/222 (0%) 0
    Herpes zoster 3/434 (0.7%) 3 0/222 (0%) 0
    Infection 1/434 (0.2%) 1 0/222 (0%) 0
    Infusion site infection 1/434 (0.2%) 1 1/222 (0.5%) 1
    Lobar pneumonia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Lower respiratory tract infection 1/434 (0.2%) 1 0/222 (0%) 0
    Lymphadenitis bacterial 1/434 (0.2%) 1 0/222 (0%) 0
    Nail infection 1/434 (0.2%) 1 0/222 (0%) 0
    Nasopharyngitis 2/434 (0.5%) 2 0/222 (0%) 0
    Onychomycosis 0/434 (0%) 0 1/222 (0.5%) 1
    Oral candidiasis 16/434 (3.7%) 16 6/222 (2.7%) 6
    Oral fungal infection 1/434 (0.2%) 1 0/222 (0%) 0
    Orchitis 0/434 (0%) 0 1/222 (0.5%) 1
    Pneumonia 36/434 (8.3%) 39 8/222 (3.6%) 8
    Pneumonia staphylococcal 1/434 (0.2%) 1 0/222 (0%) 0
    Pneumonia streptococcal 1/434 (0.2%) 1 0/222 (0%) 0
    Respiratory tract infection 6/434 (1.4%) 6 1/222 (0.5%) 1
    Sepsis 3/434 (0.7%) 3 1/222 (0.5%) 1
    Sinusitis 7/434 (1.6%) 7 2/222 (0.9%) 2
    Skin infection 2/434 (0.5%) 2 2/222 (0.9%) 2
    Staphylococcal bacteraemia 0/434 (0%) 0 1/222 (0.5%) 1
    Staphylococcal infection 0/434 (0%) 0 3/222 (1.4%) 3
    Staphylococcal sepsis 0/434 (0%) 0 1/222 (0.5%) 1
    Subacute endocarditis 0/434 (0%) 0 1/222 (0.5%) 1
    Tooth abscess 0/434 (0%) 0 1/222 (0.5%) 1
    Tracheobronchitis 1/434 (0.2%) 1 0/222 (0%) 0
    Upper respiratory tract infection 2/434 (0.5%) 2 0/222 (0%) 0
    Urinary tract infection 90/434 (20.7%) 104 46/222 (20.7%) 51
    Urinary tract infection bacterial 1/434 (0.2%) 1 0/222 (0%) 0
    Urosepsis 1/434 (0.2%) 1 0/222 (0%) 0
    Vaginal candidiasis 0/434 (0%) 0 1/222 (0.5%) 1
    Vaginal infection 1/434 (0.2%) 1 0/222 (0%) 0
    Vulvovaginal mycotic infection 1/434 (0.2%) 1 0/222 (0%) 0
    Wound infection 1/434 (0.2%) 1 1/222 (0.5%) 1
    Wound infection bacterial 1/434 (0.2%) 1 0/222 (0%) 0
    Injury, poisoning and procedural complications
    Alcohol poisoning 1/434 (0.2%) 1 0/222 (0%) 0
    Brain herniation 2/434 (0.5%) 2 0/222 (0%) 0
    Conjunctival abrasion 0/434 (0%) 0 1/222 (0.5%) 1
    Contrast media reaction 1/434 (0.2%) 1 0/222 (0%) 0
    Contusion 26/434 (6%) 30 9/222 (4.1%) 12
    Device lead damage 0/434 (0%) 0 1/222 (0.5%) 1
    Difficult to wean from ventilator 1/434 (0.2%) 1 0/222 (0%) 0
    Drug administration error 1/434 (0.2%) 1 0/222 (0%) 0
    Epicondylitis 0/434 (0%) 0 1/222 (0.5%) 1
    Excoriation 3/434 (0.7%) 4 2/222 (0.9%) 2
    Fall 13/434 (3%) 15 18/222 (8.1%) 18
    Feeding tube complication 1/434 (0.2%) 1 1/222 (0.5%) 2
    Haematuria traumatic 1/434 (0.2%) 1 0/222 (0%) 0
    Hand fracture 0/434 (0%) 0 1/222 (0.5%) 1
    Incision site complication 5/434 (1.2%) 5 2/222 (0.9%) 3
    Incision site oedema 0/434 (0%) 0 1/222 (0.5%) 1
    Intubation complication 1/434 (0.2%) 1 0/222 (0%) 0
    Joint dislocation 1/434 (0.2%) 1 0/222 (0%) 0
    Joint sprain 1/434 (0.2%) 1 1/222 (0.5%) 1
    Laceration 0/434 (0%) 0 1/222 (0.5%) 1
    Medication error 2/434 (0.5%) 2 0/222 (0%) 0
    Mouth injury 0/434 (0%) 0 1/222 (0.5%) 1
    Muscle strain 0/434 (0%) 0 1/222 (0.5%) 1
    Pacemaker complication 1/434 (0.2%) 1 0/222 (0%) 0
    Periorbital haematoma 1/434 (0.2%) 1 1/222 (0.5%) 1
    Post procedural haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Post procedural haematuria 1/434 (0.2%) 1 0/222 (0%) 0
    Post procedural haemorrhage 4/434 (0.9%) 4 1/222 (0.5%) 1
    Post-traumatic pain 1/434 (0.2%) 1 0/222 (0%) 0
    Procedural complication 1/434 (0.2%) 1 0/222 (0%) 0
    Procedural hypertension 1/434 (0.2%) 1 0/222 (0%) 0
    Renal injury 1/434 (0.2%) 1 0/222 (0%) 0
    Rib fracture 1/434 (0.2%) 1 2/222 (0.9%) 2
    Skin injury 1/434 (0.2%) 1 0/222 (0%) 0
    Skin laceration 8/434 (1.8%) 9 0/222 (0%) 0
    Stress fracture 1/434 (0.2%) 1 0/222 (0%) 0
    Tracheostomy malfunction 0/434 (0%) 0 1/222 (0.5%) 1
    Transfusion reaction 1/434 (0.2%) 1 0/222 (0%) 0
    Traumatic fracture 0/434 (0%) 0 1/222 (0.5%) 1
    Traumatic haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Upper limb fracture 1/434 (0.2%) 1 0/222 (0%) 0
    Wound 1/434 (0.2%) 1 1/222 (0.5%) 1
    Wrong technique in drug usage process 1/434 (0.2%) 1 0/222 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 4/434 (0.9%) 4 0/222 (0%) 0
    Bacteria stool identified 1/434 (0.2%) 1 1/222 (0.5%) 1
    Blood albumin abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Blood alkaline phosphatase increased 1/434 (0.2%) 1 0/222 (0%) 0
    Blood cholesterol increased 0/434 (0%) 0 1/222 (0.5%) 1
    Blood creatine phosphokinase increased 0/434 (0%) 0 1/222 (0.5%) 1
    Blood creatinine increased 2/434 (0.5%) 2 1/222 (0.5%) 1
    Blood culture positive 0/434 (0%) 0 1/222 (0.5%) 1
    Blood electrolytes abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Blood fibrinogen decreased 0/434 (0%) 0 1/222 (0.5%) 1
    Blood fibrinogen increased 0/434 (0%) 0 1/222 (0.5%) 1
    Blood glucose abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Blood glucose increased 1/434 (0.2%) 1 1/222 (0.5%) 1
    Blood lactate dehydrogenase increased 1/434 (0.2%) 1 0/222 (0%) 0
    Blood magnesium decreased 8/434 (1.8%) 8 3/222 (1.4%) 3
    Blood phosphorus decreased 2/434 (0.5%) 2 2/222 (0.9%) 2
    Blood potassium decreased 2/434 (0.5%) 2 1/222 (0.5%) 1
    Blood pressure decreased 1/434 (0.2%) 1 1/222 (0.5%) 1
    Blood pressure increased 2/434 (0.5%) 2 2/222 (0.9%) 2
    Blood test abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Blood thyroid stimulating hormone decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Blood urea abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Blood urea increased 1/434 (0.2%) 1 0/222 (0%) 0
    Body temperature increased 6/434 (1.4%) 6 2/222 (0.9%) 3
    Breath sounds abnormal 1/434 (0.2%) 1 1/222 (0.5%) 3
    C-reactive protein increased 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiac enzymes increased 1/434 (0.2%) 1 0/222 (0%) 0
    Cardiac stress test abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Chest X-ray abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Computerised tomogram abnormal 3/434 (0.7%) 3 1/222 (0.5%) 1
    Culture urine positive 0/434 (0%) 0 1/222 (0.5%) 1
    Drug level fluctuating 1/434 (0.2%) 1 0/222 (0%) 0
    Electrocardiogram ST segment abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Electrocardiogram ST segment depression 1/434 (0.2%) 1 0/222 (0%) 0
    Electrocardiogram ST segment elevation 1/434 (0.2%) 1 0/222 (0%) 0
    Electroencephalogram abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Free prostate-specific antigen increased 1/434 (0.2%) 1 0/222 (0%) 0
    Full blood count abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Haematocrit decreased 3/434 (0.7%) 3 1/222 (0.5%) 1
    Haematology test abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Haemoglobin 1/434 (0.2%) 1 0/222 (0%) 0
    Haemoglobin abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Haemoglobin decreased 8/434 (1.8%) 9 2/222 (0.9%) 2
    Heart rate decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Inspiratory capacity decreased 1/434 (0.2%) 1 0/222 (0%) 0
    International normalised ratio increased 1/434 (0.2%) 1 1/222 (0.5%) 1
    Myoglobin blood increased 1/434 (0.2%) 1 0/222 (0%) 0
    NIH stroke scale score increased 1/434 (0.2%) 1 2/222 (0.9%) 2
    Neurological examination abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Oxygen saturation decreased 3/434 (0.7%) 3 0/222 (0%) 0
    Platelet count decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Platelet count increased 1/434 (0.2%) 1 0/222 (0%) 0
    Prothrombin time prolonged 1/434 (0.2%) 1 0/222 (0%) 0
    Pulmonary function test decreased 1/434 (0.2%) 1 0/222 (0%) 0
    Red blood cell count decreased 3/434 (0.7%) 3 0/222 (0%) 0
    Red blood cell sedimentation rate increased 1/434 (0.2%) 1 0/222 (0%) 0
    Residual urine volume 1/434 (0.2%) 1 0/222 (0%) 0
    Scan with contrast abnormal 1/434 (0.2%) 1 0/222 (0%) 0
    Troponin I increased 1/434 (0.2%) 1 0/222 (0%) 0
    Troponin increased 10/434 (2.3%) 10 3/222 (1.4%) 3
    Urine output decreased 1/434 (0.2%) 1 2/222 (0.9%) 2
    Urine output increased 1/434 (0.2%) 1 0/222 (0%) 0
    Venous pressure jugular increased 0/434 (0%) 0 1/222 (0.5%) 1
    Weight decreased 2/434 (0.5%) 2 0/222 (0%) 0
    Weight increased 1/434 (0.2%) 1 0/222 (0%) 0
    White blood cell count increased 13/434 (3%) 13 3/222 (1.4%) 3
    Metabolism and nutrition disorders
    Anorexia 1/434 (0.2%) 1 2/222 (0.9%) 2
    Appetite disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Dehydration 5/434 (1.2%) 5 3/222 (1.4%) 3
    Diabetes mellitus 3/434 (0.7%) 3 2/222 (0.9%) 2
    Diabetes mellitus non-insulin-dependent 2/434 (0.5%) 2 1/222 (0.5%) 1
    Electrolyte imbalance 23/434 (5.3%) 25 7/222 (3.2%) 7
    Fluid imbalance 1/434 (0.2%) 1 0/222 (0%) 0
    Fluid overload 0/434 (0%) 0 1/222 (0.5%) 1
    Fluid retention 0/434 (0%) 0 2/222 (0.9%) 2
    Gout 3/434 (0.7%) 3 3/222 (1.4%) 3
    Hyperammonaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Hyperchloraemia 1/434 (0.2%) 1 0/222 (0%) 0
    Hypercholesterolaemia 3/434 (0.7%) 3 1/222 (0.5%) 1
    Hyperglycaemia 31/434 (7.1%) 31 11/222 (5%) 11
    Hyperhomocysteinaemia 1/434 (0.2%) 1 0/222 (0%) 0
    Hyperkalaemia 2/434 (0.5%) 2 2/222 (0.9%) 2
    Hyperlipidaemia 5/434 (1.2%) 5 10/222 (4.5%) 10
    Hypernatraemia 3/434 (0.7%) 3 3/222 (1.4%) 3
    Hypoalbuminaemia 3/434 (0.7%) 3 1/222 (0.5%) 1
    Hypocalcaemia 8/434 (1.8%) 8 1/222 (0.5%) 1
    Hypoglycaemia 5/434 (1.2%) 5 1/222 (0.5%) 1
    Hypokalaemia 40/434 (9.2%) 40 18/222 (8.1%) 20
    Hypomagnesaemia 3/434 (0.7%) 3 0/222 (0%) 0
    Hyponatraemia 14/434 (3.2%) 14 7/222 (3.2%) 7
    Hypophosphataemia 2/434 (0.5%) 2 0/222 (0%) 0
    Hypovolaemia 2/434 (0.5%) 2 0/222 (0%) 0
    Lactose intolerance 1/434 (0.2%) 1 0/222 (0%) 0
    Malnutrition 3/434 (0.7%) 3 2/222 (0.9%) 2
    Metabolic acidosis 1/434 (0.2%) 1 0/222 (0%) 0
    Metabolic alkalosis 1/434 (0.2%) 1 0/222 (0%) 0
    Vitamin D deficiency 5/434 (1.2%) 5 5/222 (2.3%) 5
    Musculoskeletal and connective tissue disorders
    Arthralgia 22/434 (5.1%) 25 7/222 (3.2%) 7
    Back pain 23/434 (5.3%) 24 13/222 (5.9%) 13
    Buttock pain 1/434 (0.2%) 1 0/222 (0%) 0
    Flank pain 4/434 (0.9%) 4 0/222 (0%) 0
    Groin pain 4/434 (0.9%) 4 2/222 (0.9%) 2
    Haemarthrosis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Joint effusion 1/434 (0.2%) 1 0/222 (0%) 0
    Joint swelling 2/434 (0.5%) 2 0/222 (0%) 0
    Limb discomfort 0/434 (0%) 0 1/222 (0.5%) 1
    Monarthritis 1/434 (0.2%) 1 0/222 (0%) 0
    Muscle haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Muscle spasms 1/434 (0.2%) 1 5/222 (2.3%) 6
    Muscle twitching 3/434 (0.7%) 3 1/222 (0.5%) 1
    Muscular weakness 1/434 (0.2%) 1 0/222 (0%) 0
    Musculoskeletal chest pain 2/434 (0.5%) 2 3/222 (1.4%) 3
    Musculoskeletal disorder 0/434 (0%) 0 1/222 (0.5%) 1
    Musculoskeletal pain 18/434 (4.1%) 18 8/222 (3.6%) 8
    Musculoskeletal stiffness 0/434 (0%) 0 1/222 (0.5%) 1
    Myalgia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Neck pain 7/434 (1.6%) 7 5/222 (2.3%) 5
    Pain in extremity 28/434 (6.5%) 31 12/222 (5.4%) 17
    Pain in jaw 4/434 (0.9%) 4 0/222 (0%) 0
    Periarthritis 0/434 (0%) 0 1/222 (0.5%) 1
    Rheumatoid arthritis 1/434 (0.2%) 1 0/222 (0%) 0
    Rotator cuff syndrome 1/434 (0.2%) 1 0/222 (0%) 0
    Sacral pain 0/434 (0%) 0 1/222 (0.5%) 1
    Spinal disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Trigger finger 1/434 (0.2%) 1 0/222 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chondromatosis 1/434 (0.2%) 1 0/222 (0%) 0
    Colon cancer recurrent 0/434 (0%) 0 1/222 (0.5%) 1
    Thyroid neoplasm 2/434 (0.5%) 2 0/222 (0%) 0
    Nervous system disorders
    Amnesia 3/434 (0.7%) 3 0/222 (0%) 0
    Aphasia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Balance disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Brain oedema 10/434 (2.3%) 10 15/222 (6.8%) 16
    Carotid arterial embolus 0/434 (0%) 0 1/222 (0.5%) 1
    Carotid artery dissection 7/434 (1.6%) 8 0/222 (0%) 0
    Carotid artery stenosis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cerebellar haemorrhage 0/434 (0%) 0 1/222 (0.5%) 1
    Cerebral artery embolism 5/434 (1.2%) 5 0/222 (0%) 0
    Cerebral haemorrhage 26/434 (6%) 26 7/222 (3.2%) 7
    Cerebral infarction 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cerebrovascular accident 4/434 (0.9%) 4 1/222 (0.5%) 2
    Cerebrovascular spasm 1/434 (0.2%) 1 0/222 (0%) 0
    Cognitive disorder 2/434 (0.5%) 2 1/222 (0.5%) 1
    Complex regional pain syndrome 0/434 (0%) 0 1/222 (0.5%) 1
    Convulsion 16/434 (3.7%) 19 5/222 (2.3%) 5
    Coordination abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Depressed level of consciousness 3/434 (0.7%) 3 1/222 (0.5%) 1
    Disturbance in attention 1/434 (0.2%) 1 0/222 (0%) 0
    Dizziness 15/434 (3.5%) 17 1/222 (0.5%) 1
    Dysgeusia 2/434 (0.5%) 2 0/222 (0%) 0
    Dystonia 1/434 (0.2%) 1 0/222 (0%) 0
    Encephalomalacia 1/434 (0.2%) 1 0/222 (0%) 0
    Encephalopathy 1/434 (0.2%) 1 0/222 (0%) 0
    Facial palsy 1/434 (0.2%) 1 0/222 (0%) 0
    Grand mal convulsion 1/434 (0.2%) 1 0/222 (0%) 0
    Haemorrhage intracranial 43/434 (9.9%) 43 14/222 (6.3%) 14
    Haemorrhagic cerebral infarction 1/434 (0.2%) 1 1/222 (0.5%) 1
    Haemorrhagic stroke 3/434 (0.7%) 3 1/222 (0.5%) 1
    Haemorrhagic transformation stroke 35/434 (8.1%) 35 18/222 (8.1%) 18
    Headache 80/434 (18.4%) 86 51/222 (23%) 55
    Hemiparesis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Hydrocephalus 1/434 (0.2%) 1 1/222 (0.5%) 1
    Hypoaesthesia 3/434 (0.7%) 4 2/222 (0.9%) 2
    Intention tremor 1/434 (0.2%) 1 0/222 (0%) 0
    Intracranial aneurysm 1/434 (0.2%) 1 0/222 (0%) 0
    Intracranial haematoma 1/434 (0.2%) 1 0/222 (0%) 0
    Intraventricular haemorrhage 2/434 (0.5%) 2 0/222 (0%) 0
    Lethargy 5/434 (1.2%) 6 5/222 (2.3%) 5
    Loss of consciousness 0/434 (0%) 0 1/222 (0.5%) 1
    Mental impairment 2/434 (0.5%) 2 1/222 (0.5%) 1
    Muscle spasticity 3/434 (0.7%) 3 2/222 (0.9%) 2
    Neurological symptom 12/434 (2.8%) 12 5/222 (2.3%) 5
    Neuropathy 0/434 (0%) 0 1/222 (0.5%) 1
    Paraesthesia 5/434 (1.2%) 5 0/222 (0%) 0
    Partial seizures 3/434 (0.7%) 3 1/222 (0.5%) 1
    Presyncope 1/434 (0.2%) 1 1/222 (0.5%) 1
    Putamen haemorrhage 0/434 (0%) 0 1/222 (0.5%) 1
    Restless legs syndrome 1/434 (0.2%) 1 0/222 (0%) 0
    Sciatica 1/434 (0.2%) 1 0/222 (0%) 0
    Sensory loss 1/434 (0.2%) 1 1/222 (0.5%) 1
    Somnolence 4/434 (0.9%) 4 4/222 (1.8%) 4
    Subarachnoid haemorrhage 8/434 (1.8%) 8 2/222 (0.9%) 2
    Syncope 4/434 (0.9%) 4 2/222 (0.9%) 2
    Transient ischaemic attack 6/434 (1.4%) 6 1/222 (0.5%) 1
    Tremor 5/434 (1.2%) 5 2/222 (0.9%) 2
    Unresponsive to stimuli 0/434 (0%) 0 1/222 (0.5%) 1
    Vascular dementia 1/434 (0.2%) 1 0/222 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 1/434 (0.2%) 1 0/222 (0%) 0
    Psychiatric disorders
    Acute psychosis 1/434 (0.2%) 1 0/222 (0%) 0
    Aggression 2/434 (0.5%) 2 0/222 (0%) 0
    Agitation 31/434 (7.1%) 32 18/222 (8.1%) 19
    Alcohol withdrawal syndrome 1/434 (0.2%) 1 2/222 (0.9%) 2
    Anxiety 24/434 (5.5%) 25 10/222 (4.5%) 11
    Bruxism 0/434 (0%) 0 1/222 (0.5%) 1
    Catatonia 1/434 (0.2%) 1 0/222 (0%) 0
    Confusional state 6/434 (1.4%) 6 0/222 (0%) 0
    Delirium 5/434 (1.2%) 5 1/222 (0.5%) 1
    Delirium tremens 1/434 (0.2%) 1 0/222 (0%) 0
    Depressed mood 0/434 (0%) 0 2/222 (0.9%) 2
    Depression 43/434 (9.9%) 44 18/222 (8.1%) 19
    Disorientation 1/434 (0.2%) 1 0/222 (0%) 0
    Dysthymic disorder 0/434 (0%) 0 1/222 (0.5%) 1
    Emotional disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Hallucination 7/434 (1.6%) 7 1/222 (0.5%) 1
    Hallucination, visual 1/434 (0.2%) 1 0/222 (0%) 0
    Hallucinations, mixed 0/434 (0%) 0 1/222 (0.5%) 1
    Impulsive behaviour 1/434 (0.2%) 1 0/222 (0%) 0
    Insomnia 26/434 (6%) 28 11/222 (5%) 11
    Insomnia related to another mental condition 1/434 (0.2%) 1 0/222 (0%) 0
    Mental status changes 4/434 (0.9%) 4 6/222 (2.7%) 7
    Osmophobia 1/434 (0.2%) 1 0/222 (0%) 0
    Panic attack 3/434 (0.7%) 3 1/222 (0.5%) 1
    Posturing 1/434 (0.2%) 1 0/222 (0%) 0
    Psychotic disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Restlessness 3/434 (0.7%) 3 6/222 (2.7%) 6
    Suicidal ideation 1/434 (0.2%) 1 0/222 (0%) 0
    Renal and urinary disorders
    Azotaemia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Bladder disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Dysuria 2/434 (0.5%) 2 2/222 (0.9%) 2
    Haematuria 24/434 (5.5%) 25 13/222 (5.9%) 13
    Hypertonic bladder 2/434 (0.5%) 2 0/222 (0%) 0
    Incontinence 2/434 (0.5%) 2 0/222 (0%) 0
    Nephrolithiasis 1/434 (0.2%) 1 0/222 (0%) 0
    Neurogenic bladder 2/434 (0.5%) 2 1/222 (0.5%) 1
    Oliguria 6/434 (1.4%) 6 2/222 (0.9%) 2
    Pollakiuria 1/434 (0.2%) 1 0/222 (0%) 0
    Proteinuria 1/434 (0.2%) 1 0/222 (0%) 0
    Renal disorder 1/434 (0.2%) 1 0/222 (0%) 0
    Renal failure 4/434 (0.9%) 4 2/222 (0.9%) 2
    Renal failure acute 6/434 (1.4%) 6 1/222 (0.5%) 1
    Renal impairment 0/434 (0%) 0 1/222 (0.5%) 1
    Urethral discharge 1/434 (0.2%) 1 0/222 (0%) 0
    Urinary incontinence 7/434 (1.6%) 7 2/222 (0.9%) 2
    Urinary retention 13/434 (3%) 13 6/222 (2.7%) 7
    Urine odour abnormal 0/434 (0%) 0 1/222 (0.5%) 1
    Urogenital haemorrhage 0/434 (0%) 0 1/222 (0.5%) 1
    Reproductive system and breast disorders
    Adnexa uteri mass 1/434 (0.2%) 1 0/222 (0%) 0
    Benign prostatic hyperplasia 1/434 (0.2%) 1 0/222 (0%) 0
    Breast mass 1/434 (0.2%) 1 0/222 (0%) 0
    Dysmenorrhoea 1/434 (0.2%) 1 0/222 (0%) 0
    Female genital tract fistula 0/434 (0%) 0 1/222 (0.5%) 1
    Genital haemorrhage 1/434 (0.2%) 1 0/222 (0%) 0
    Menorrhagia 0/434 (0%) 0 1/222 (0.5%) 1
    Penile swelling 0/434 (0%) 0 1/222 (0.5%) 1
    Prostatitis 1/434 (0.2%) 1 0/222 (0%) 0
    Scrotal erythema 0/434 (0%) 0 1/222 (0.5%) 1
    Vaginal haemorrhage 2/434 (0.5%) 2 1/222 (0.5%) 1
    Vaginal pain 0/434 (0%) 0 1/222 (0.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/434 (0%) 0 1/222 (0.5%) 1
    Acute respiratory failure 2/434 (0.5%) 2 0/222 (0%) 0
    Apnoea 3/434 (0.7%) 3 2/222 (0.9%) 2
    Aspiration 7/434 (1.6%) 7 0/222 (0%) 0
    Atelectasis 8/434 (1.8%) 8 4/222 (1.8%) 4
    Bronchospasm 0/434 (0%) 0 1/222 (0.5%) 1
    Cheyne-Stokes respiration 0/434 (0%) 0 1/222 (0.5%) 1
    Choking 1/434 (0.2%) 1 0/222 (0%) 0
    Chronic obstructive pulmonary disease 1/434 (0.2%) 1 1/222 (0.5%) 1
    Cough 9/434 (2.1%) 9 1/222 (0.5%) 1
    Dry throat 1/434 (0.2%) 1 0/222 (0%) 0
    Dyspnoea 7/434 (1.6%) 7 8/222 (3.6%) 8
    Dyspnoea exertional 0/434 (0%) 0 1/222 (0.5%) 1
    Emphysema 0/434 (0%) 0 1/222 (0.5%) 1
    Epistaxis 17/434 (3.9%) 18 2/222 (0.9%) 2
    Haemoptysis 5/434 (1.2%) 5 2/222 (0.9%) 2
    Hiccups 2/434 (0.5%) 2 2/222 (0.9%) 2
    Hypoventilation 1/434 (0.2%) 1 1/222 (0.5%) 1
    Hypoxia 7/434 (1.6%) 7 3/222 (1.4%) 3
    Increased bronchial secretion 1/434 (0.2%) 1 0/222 (0%) 0
    Increased viscosity of bronchial secretion 1/434 (0.2%) 1 0/222 (0%) 0
    Lung infiltration 2/434 (0.5%) 2 0/222 (0%) 0
    Nasal congestion 1/434 (0.2%) 1 0/222 (0%) 0
    Nasal dryness 0/434 (0%) 0 2/222 (0.9%) 2
    Nocturnal dyspnoea 1/434 (0.2%) 1 0/222 (0%) 0
    Pharyngolaryngeal pain 4/434 (0.9%) 4 1/222 (0.5%) 1
    Pleural effusion 8/434 (1.8%) 8 4/222 (1.8%) 4
    Pneumonia aspiration 13/434 (3%) 16 10/222 (4.5%) 10
    Pneumothorax 2/434 (0.5%) 2 0/222 (0%) 0
    Productive cough 1/434 (0.2%) 1 2/222 (0.9%) 2
    Pulmonary congestion 4/434 (0.9%) 4 0/222 (0%) 0
    Pulmonary embolism 4/434 (0.9%) 4 0/222 (0%) 0
    Pulmonary hypertension 2/434 (0.5%) 2 0/222 (0%) 0
    Pulmonary oedema 21/434 (4.8%) 22 1/222 (0.5%) 1
    Rales 2/434 (0.5%) 2 1/222 (0.5%) 1
    Respiratory alkalosis 0/434 (0%) 0 1/222 (0.5%) 1
    Respiratory disorder 1/434 (0.2%) 1 1/222 (0.5%) 1
    Respiratory distress 5/434 (1.2%) 5 2/222 (0.9%) 2
    Respiratory failure 10/434 (2.3%) 10 3/222 (1.4%) 3
    Respiratory tract congestion 8/434 (1.8%) 8 4/222 (1.8%) 4
    Rhonchi 2/434 (0.5%) 2 2/222 (0.9%) 3
    Sleep apnoea syndrome 3/434 (0.7%) 3 0/222 (0%) 0
    Tachypnoea 8/434 (1.8%) 9 2/222 (0.9%) 2
    Tracheal oedema 1/434 (0.2%) 1 0/222 (0%) 0
    Upper airway resistance syndrome 1/434 (0.2%) 1 0/222 (0%) 0
    Upper respiratory tract congestion 1/434 (0.2%) 1 1/222 (0.5%) 1
    Vocal cord cyst 1/434 (0.2%) 1 0/222 (0%) 0
    Wheezing 8/434 (1.8%) 8 1/222 (0.5%) 1
    Skin and subcutaneous tissue disorders
    Angioneurotic oedema 2/434 (0.5%) 2 0/222 (0%) 0
    Blister 2/434 (0.5%) 2 1/222 (0.5%) 1
    Decubitus ulcer 5/434 (1.2%) 7 4/222 (1.8%) 4
    Dermatitis 0/434 (0%) 0 1/222 (0.5%) 1
    Dermatitis allergic 1/434 (0.2%) 3 0/222 (0%) 0
    Dermatitis contact 1/434 (0.2%) 1 2/222 (0.9%) 2
    Dry skin 1/434 (0.2%) 1 2/222 (0.9%) 2
    Ecchymosis 6/434 (1.4%) 6 6/222 (2.7%) 9
    Erythema 5/434 (1.2%) 6 2/222 (0.9%) 3
    Hyperhidrosis 2/434 (0.5%) 2 1/222 (0.5%) 1
    Melanosis 1/434 (0.2%) 1 0/222 (0%) 0
    Periorbital oedema 1/434 (0.2%) 1 1/222 (0.5%) 1
    Petechiae 1/434 (0.2%) 1 2/222 (0.9%) 2
    Pruritus 2/434 (0.5%) 2 0/222 (0%) 0
    Pruritus generalised 0/434 (0%) 0 1/222 (0.5%) 1
    Psoriasis 2/434 (0.5%) 2 0/222 (0%) 0
    Rash 17/434 (3.9%) 17 8/222 (3.6%) 8
    Rash erythematous 1/434 (0.2%) 2 0/222 (0%) 0
    Rash generalised 1/434 (0.2%) 1 0/222 (0%) 0
    Rash pruritic 1/434 (0.2%) 1 0/222 (0%) 0
    Skin disorder 6/434 (1.4%) 7 3/222 (1.4%) 4
    Skin haemorrhage 1/434 (0.2%) 1 3/222 (1.4%) 3
    Skin irritation 1/434 (0.2%) 1 0/222 (0%) 0
    Skin ulcer 1/434 (0.2%) 1 1/222 (0.5%) 1
    Swelling face 0/434 (0%) 0 1/222 (0.5%) 1
    Urticaria 4/434 (0.9%) 4 1/222 (0.5%) 1
    Social circumstances
    Drug abuser 0/434 (0%) 0 1/222 (0.5%) 1
    Inadequate diet 0/434 (0%) 0 1/222 (0.5%) 1
    Surgical and medical procedures
    Atrial septal defect repair 0/434 (0%) 0 1/222 (0.5%) 1
    Cardiac pacemaker insertion 1/434 (0.2%) 1 0/222 (0%) 0
    Carotid endarterectomy 1/434 (0.2%) 1 2/222 (0.9%) 2
    Cataract operation 0/434 (0%) 0 1/222 (0.5%) 1
    Cerebral oedema management 2/434 (0.5%) 2 0/222 (0%) 0
    Cranioplasty 1/434 (0.2%) 1 1/222 (0.5%) 1
    Gastrointestinal tube removal 0/434 (0%) 0 1/222 (0.5%) 1
    Gastrostomy tube insertion 1/434 (0.2%) 1 0/222 (0%) 0
    High frequency ablation 1/434 (0.2%) 1 0/222 (0%) 0
    Knee arthroplasty 1/434 (0.2%) 1 0/222 (0%) 0
    Mitral valve replacement 0/434 (0%) 0 1/222 (0.5%) 1
    Peripheral nerve decompression 1/434 (0.2%) 1 0/222 (0%) 0
    Skin neoplasm excision 0/434 (0%) 0 1/222 (0.5%) 1
    Surgery 1/434 (0.2%) 1 0/222 (0%) 0
    Toe amputation 1/434 (0.2%) 1 0/222 (0%) 0
    Vascular disorders
    Accelerated hypertension 1/434 (0.2%) 1 0/222 (0%) 0
    Aortic aneurysm 1/434 (0.2%) 1 0/222 (0%) 0
    Aortic arteriosclerosis 1/434 (0.2%) 1 1/222 (0.5%) 1
    Artery dissection 2/434 (0.5%) 2 0/222 (0%) 0
    Deep vein thrombosis 11/434 (2.5%) 11 1/222 (0.5%) 1
    Femoral artery dissection 1/434 (0.2%) 1 0/222 (0%) 0
    Haematoma 14/434 (3.2%) 16 5/222 (2.3%) 6
    Haemorrhage 5/434 (1.2%) 5 0/222 (0%) 0
    Haemorrhagic infarction 1/434 (0.2%) 1 0/222 (0%) 0
    Hypertension 30/434 (6.9%) 32 16/222 (7.2%) 16
    Hypotension 34/434 (7.8%) 34 23/222 (10.4%) 23
    Labile blood pressure 1/434 (0.2%) 1 0/222 (0%) 0
    Labile hypertension 3/434 (0.7%) 3 1/222 (0.5%) 1
    Orthostatic hypotension 2/434 (0.5%) 2 1/222 (0.5%) 1
    Peripheral artery aneurysm 1/434 (0.2%) 1 0/222 (0%) 0
    Peripheral ischaemia 1/434 (0.2%) 1 1/222 (0.5%) 1
    Peripheral vascular disorder 1/434 (0.2%) 1 1/222 (0.5%) 1
    Thrombophlebitis superficial 3/434 (0.7%) 3 1/222 (0.5%) 1
    Vascular pseudoaneurysm 1/434 (0.2%) 1 0/222 (0%) 0
    Vascular rupture 1/434 (0.2%) 1 0/222 (0%) 0
    Venous thrombosis limb 0/434 (0%) 0 1/222 (0.5%) 1

    Limitations/Caveats

    The IMS III trial was stopped early because of futility, according to the prespecified rules. A limitation of our trial is that it did not compare the efficacy of the new stent retrievers with that of intravenous t-PA alone.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    No publication will be authored prior to 12 mos after publication of the primary results without consent of the Publications Subcommittee. 12 mos after this time an Investigator may publish the results at the Collaborating Institution. No institution involved may be restricted from publishing independently 12 mos from publication of the primary paper. After 12 mo all manuscripts from the study must be submitted to the PI/Publications Subcommittee 45 days prior to any submission.

    Results Point of Contact

    Name/Title Joseph P. Broderick
    Organization University of Cincinnati Academic Health Center
    Phone 513-558-5429
    Email broderjp@ucmail.uc.edu
    Responsible Party:
    Joseph Broderick, Professor and Chairman Department of Neurology, University of Cincinnati
    ClinicalTrials.gov Identifier:
    NCT00359424
    Other Study ID Numbers:
    • U01NS052220
    • U01NS052220
    • U01NS054630
    • 2009-017454-12
    First Posted:
    Aug 2, 2006
    Last Update Posted:
    Dec 13, 2013
    Last Verified:
    Nov 1, 2013