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

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

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
Overall Participants Analyzed  [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)
[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.
Time from stroke onset to initiation of IV rt-PA [1]  [Units: Minutes] Mean (Standard Deviation)	122.4  (33.7)	121.2  (33.8)	122.0  (33.7)
[1] Time from stroke onset to initiation of intravenous (IV) rt-PA in minutes.
NIHSS Score Strata  [Units: Participants]
NIHSS Score <20	302	150	452
NIHSS Score > = 20	132	72	204

1.  Primary:

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

2.  Primary:

Death Due to Any Cause   [ Time Frame: within 90 days post randomization ]

3.  Primary:

Symptomatic Intracranial Hemorrhage   [ Time Frame: within the first 30 hours post IV rt-PA ]

4.  Secondary:

Incidence of Parenchymal Type II (PH2) Hematomas   [ Time Frame: within 30 hours post IV rt-PA ]

5.  Secondary:

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

6.  Secondary:

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

7.  Secondary:

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

8.  Secondary:

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

9.  Secondary:

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

10.  Secondary:

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

11.  Secondary:

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

12.  Secondary:

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

13.  Secondary:

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

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.