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

This study has been terminated.
(NINDS/NIH-DSMB recommended halting trial due to futility, no safety concerns.)
Sponsor:
Collaborators:
Medical University of South Carolina
University of Calgary
Information provided by (Responsible Party):
Joseph Broderick, University of Cincinnati
ClinicalTrials.gov Identifier:
NCT00359424
First received: July 31, 2006
Last updated: November 19, 2013
Last verified: November 2013
Results First Received: July 4, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Stroke
Interventions: Drug: IV rt-PA alone
Other: endovascular therapy

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

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 Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Endovascular Therapy 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 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.

Participant Flow:   Overall Study
    Endovascular Therapy     IV Rt-PA Alone  
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  
Death                 99                 58  
Lost to Follow-up                 19                 7  
Withdrawal by Subject                 10                 2  
follow up not conducted                 2                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
A sample of 900 was calculated to provide an effect size of 10 percentage points assuming that 40% of the patients had a good outcome in the IV t-PA group, as noted in patients in the NINDS rt-PA Stroke Study who had age and baseline stroke severity similar to the eligibility criteria for the IMS3 trial. The trial was halted at 656 subjects.

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.
Total Total of all reporting groups

Baseline Measures
    Endovascular Therapy     IV Rt-PA Alone     Total  
Number of Participants  
[units: participants]
  434     222     656  
Age  
[units: years]
Median ( Full Range )
  69  
  ( 23 to 89 )  
  68  
  ( 23 to 84 )  
  69  
  ( 23 to 89 )  
Gender  
[units: participants]
     
Female     216     100     316  
Male     218     122     340  
NIHSS Score [1]
[units: Score on a scale]
Median ( Full Range )
  17  
  ( 7 to 40 )  
  16  
  ( 8 to 30 )  
  17  
  ( 7 to 40 )  
Time from stroke onset to initiation of IV rt-PA [2]
[units: minutes]
Mean ± Standard Deviation
  122.4  ± 33.7     121.2  ± 33.8     122.0  ± 33.7  
NIHSS Score Strata  
[units: participants]
     
NIHSS Score <20     302     150     452  
NIHSS Score > = 20     132     72     204  
[1]

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.

[2] Time from stroke onset to initiation of intravenous (IV) rt-PA in minutes.



  Outcome Measures
  Hide All Outcome Measures

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

Measure Type Primary
Measure Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2.
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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)

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2.  
[units: participants]
   
mRS 0-2     177     86  
mRS 3-6     257     136  


Statistical Analysis 1 for Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2.
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] .7031
Risk Difference (RD) [4] 1.5
95% Confidence Interval ( -6.1 to 9.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cochran-Mantel-Haenszel (CMH) test adjusting for the dichotomized baseline NIHSS score (<20 or ≥20).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[4] Other relevant estimation information:
  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:   Death Due to Any Cause   [ Time Frame: within 90 days post randomization ]

Measure Type Primary
Measure Title Death Due to Any Cause
Measure Description No text entered.
Time Frame within 90 days post randomization  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Death Due to Any Cause  
[units: participants]
  83     48  


Statistical Analysis 1 for Death Due to Any Cause
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] .5241
Risk Difference (RD) [4] -2.0
99% Confidence Interval ( -10.3 to 6.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cochran-Mantel-Haenszel (CMH) test adjusting for the dichotomized baseline NIHSS score (<20 or ≥20).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The CMH statistic is tested at the two-sided alpha level of 0.01.
[4] Other relevant estimation information:
  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:   Symptomatic Intracranial Hemorrhage   [ Time Frame: within the first 30 hours post IV rt-PA ]

Measure Type Primary
Measure Title Symptomatic Intracranial Hemorrhage
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Symptomatic Intracranial Hemorrhage  
[units: participants]
  27     13  


Statistical Analysis 1 for Symptomatic Intracranial Hemorrhage
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] .8275
Risk Difference (RD) [4] .4
99% Confidence Interval ( -4.6 to 5.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cochran-Mantel-Haenszel (CMH) test adjusting for the dichotomized baseline NIHSS score (<20 or ≥20).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The CMH statistic is tested at the two-sided alpha level of 0.01.
[4] Other relevant estimation information:
  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:   Incidence of Parenchymal Type II (PH2) Hematomas   [ Time Frame: within 30 hours post IV rt-PA ]

Measure Type Secondary
Measure Title Incidence of Parenchymal Type II (PH2) Hematomas
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  417     207  
Incidence of Parenchymal Type II (PH2) Hematomas  
[units: participants]
  25     13  

No statistical analysis provided for Incidence of Parenchymal Type II (PH2) Hematomas



5.  Secondary:   Asymptomatic Intracranial Hemorrhage   [ Time Frame: within 30 hours post IV rt-PA ]

Measure Type Secondary
Measure Title Asymptomatic Intracranial Hemorrhage
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Asymptomatic Intracranial Hemorrhage  
[units: participants]
  119     42  

No statistical analysis provided for Asymptomatic Intracranial Hemorrhage



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

Measure Type Secondary
Measure Title National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater.
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater.  
[units: participants]
   
NIHSS 0-1     44     22  
NIHSS 2+     390     200  

No statistical analysis provided for National Institutes of Health Stroke Scale Score (NIHSS) >> Dichotomized 0-1 Versus 2 or Greater.



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

Measure Type Secondary
Measure Title National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater.
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater.  
[units: participants]
   
NIHSSS 0-1     120     50  
NIHSSS 2+     314     172  

No statistical analysis provided for National Institutes of Health Stroke Scale Score (NIHSS) Dichotomized 0-1 Versus 2 or Greater.



8.  Secondary:   Barthel Index (BI) Dichotomized 0-90 Versus 95-100   [ Time Frame: at 90 days post randomization ]

Measure Type Secondary
Measure Title Barthel Index (BI) Dichotomized 0-90 Versus 95-100
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Barthel Index (BI) Dichotomized 0-90 Versus 95-100  
[units: participants]
   
BI 95-100     183     86  
BI 0-90     251     136  

No statistical analysis provided for Barthel Index (BI) Dichotomized 0-90 Versus 95-100



9.  Secondary:   Trail Making Test Part A Time   [ Time Frame: 90 days post randomization ]

Measure Type Secondary
Measure Title Trail Making Test Part A Time
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants were excluded if the Trail Making Test was not assessed or if they failed to complete Part A.

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  244     127  
Trail Making Test Part A Time  
[units: seconds]
Mean ± Standard Deviation
  84.2  ± 64.3     82.0  ± 62.3  

No statistical analysis provided for Trail Making Test Part A Time



10.  Secondary:   Trail Making Test Part B Time   [ Time Frame: at 90 days post randomization ]

Measure Type Secondary
Measure Title Trail Making Test Part B Time
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants were excluded if the Trail Making Test was not assessed or if they failed to complete Part B.

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  183     92  
Trail Making Test Part B Time  
[units: seconds]
Mean ± Standard Deviation
  143.8  ± 75.3     141.3  ± 78.4  

No statistical analysis provided for Trail Making Test Part B Time



11.  Secondary:   Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2   [ Time Frame: at 180 days ]

Measure Type Secondary
Measure Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2  
[units: participants]
   
mRS 0-2     179     86  
mRS 3-6     255     136  

No statistical analysis provided for Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2



12.  Secondary:   Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2   [ Time Frame: 270 days ]

Measure Type Secondary
Measure Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2  
[units: participants]
   
mRS 0-2     177     88  
mRS 3-6     257     134  

No statistical analysis provided for Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2



13.  Secondary:   Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2   [ Time Frame: 360 days post randomization ]

Measure Type Secondary
Measure Title Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
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.
IV Rt-PA Alone Group one will receive the standard dose of intravenous (IV) rt-PA alone given over an hour.

Measured Values
    Endovascular Therapy     IV Rt-PA Alone  
Number of Participants Analyzed  
[units: participants]
  434     222  
Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2  
[units: participants]
   
mRS 0-2     191     95  
mRS 3-6     243     127  

No statistical analysis provided for Modified Rankin Scale (mRS) Score Dichotomized to 0-2 Versus Greater Than 2




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


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