The clinical practice of acute ischemic stroke is at a critical juncture. The use of dot-removal devices approved by the FDA is rapidly expanding, and more devices are poised to enter clinical practice in next several years. This major change in clinical practice has accelerated since 2004 after the approval of the first FDA-cleared device for thrombus removal in acute stroke patients and is occurring without clinical data demonstrating that these devices improve patient outcome as compared to standard therapy (IV rt-PA within three hours of onset). The ongoing multicenter Interventional Management of Stroke (IMS) III Trial is the only randomized Phase III trial that compares the standard therapy to an approach that combines IV rt-PA followed by lA removal of thrombus by devices and/or lA rt-PA. Data from this Trial are critical to inform clinical and public health policy decisions regarding the roe of endovascular therapy for acute ischemic stroke. The primary objective of the IMS III Trial is to determine if ischemic stroke subjects with a baseline NIHSS scores 10, or with an NIHSSSof 8-9 with evidence of MCA, ICA, or basilar artery occlusion by CTA, treated with the combined IV+IA approach started within 3 hours of onset, are more likely to have a favorable outcome, defined as a modified Rankin Scale score of 0-2 assessed at 90 days from randomization, as compared to subjects treated with standard IV rt-PA. The two treatment groups also are compared with regard to additional clinical outcome measures, imaging, and safety data. In addiiton, cost effectiveness of the combined IV+IA approach is evaluated. The Trial currently is supported by two NINDS cooperative agreement grants: (1) to the University of Cincinnati Clinical Coordinating and Angiographic Imaging Center (PI: Joseph P. Broderick, MD) to provide clinical leadership and project and site management;and (2) to the Statistical and Data Coordinating Center (SDCC) at the Medical University of South Carolina (PI: Yuko Y. Palesch, PhD) to provide data management and statistical expertise. The purpose of this competitive renewal application from the SDCC is to closely collaborate with the Trial investigators to bring the IMS III Trial to successful completion with data quality of the highest standard.

Public Health Relevance

Recently, the FDA has approved increasing number of devices to remove the clot in acute ischemic stroke patients, but no study to date has demonstrated that these devices improve patient outcomes. The purpose of the IMS III Trial is to definitively determine whether or not the use of these devices, in addition to the current standard treatment with intravenous rt-PA, results in better patient outcome (assessed at 90 days) compared to current standard treatment with intravenous rt-PA alone.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS077304-02
Application #
8337859
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Gilbert, Peter R
Project Start
2011-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$650,000
Indirect Cost
$207,647
Name
Medical University of South Carolina
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Liebeskind, David S; Tomsick, Thomas A; Foster, Lydia D et al. (2014) Collaterals at angiography and outcomes in the Interventional Management of Stroke (IMS) III trial. Stroke 45:759-64
Simpson, Kit N; Simpson, Annie N; Mauldin, Patrick D et al. (2014) Drivers of costs associated with reperfusion therapy in acute stroke: the Interventional Management of Stroke III Trial. Stroke 45:1791-8
Goyal, Mayank; Almekhlafi, Mohammed A; Fan, Liqiong et al. (2014) Evaluation of interval times from onset to reperfusion in patients undergoing endovascular therapy in the Interventional Management of Stroke III trial. Circulation 130:265-72
Yeatts, Sharon D; Martin, Renee H; Coffey, Christopher S et al. (2014) Challenges of decision making regarding futility in a randomized trial: the Interventional Management of Stroke III experience. Stroke 45:1408-14
Broderick, Joseph P; Palesch, Yuko Y; Demchuk, Andrew M et al. (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893-903
Yeatts, Sharon D (2013) Novel methodologic approaches to phase I, II, and III trials. Stroke 44:S116-8