Abstract

Intravenous recombinant tissue plasminogen activator (IV rt-PA) is an effective therapy for acute ischemic stroke but has substantial limitations when used alone to open occluded major extracranial and intracranial arteries. The EMS and IMS I Pilot Studies (with over 120 subjects), as well clinical series from various centers, demonstrate that a combined intravenous (IV) and intra-arterial (IA) approach to recanalization, using rt-PA administered within three hours of onset, is as safe and may have improved efficacy as compared to full-dose IV rt-PA as administered during the NINDS rt-PA Stroke Trial. The Interventional Management of Stroke (IMS) III Trial is a randomized, open-label, multi-center study with a maximum of 900 subjects with acute ischemic stroke who are eligible to receive IV rt-PA within 3 hours of symptom onset and whose baseline NIH Stroke Scale score (NIHSSS) is equal to or greater than 10. The primary goal of the IMS III Trial is to determine if ischemic stroke subjects treated with rt-PA, utilizing a combined IV/IA approach to recanalization started within 3 hours of onset, are more likely to have a favorable outcome at 3 months (Rankin 0-2) as compared to subjects treated with standard IV rt-PA alone. The primary measures of safety will be mortality at 3 months and the presence of symptomatic ICH within the first 36 hours from randomization. In addition to other clinical and imaging endpoints, the economic impact of the IV/IA therapy will be evaluated. The study will use stratified randomization in which subjects with a baseline NIHSSS of 10-19 will be randomized in a 1:1 ratio and subjects with NIHSSS >20 will be randomized to a 2:1 ratio with more in the IV/IA group. A primary subgroup analysis will be conducted on the second stratum of subjects with an NIHSS > 20. The trial is open-label since blinding of the intervention is not possible but the primary 3-month and secondary endpoints will be done by an investigator blinded to treatment assignment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS052220-02
Application #
7121176
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Galpern, Wendy R
Project Start
2005-09-15
Project End
2010-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
2
Fiscal Year
2007
Total Cost
$2,000,001
Indirect Cost

  Institution

Name
University of Cincinnati
Department
Neurology
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221

  Publications

Vagal, Achala; Menon, Bijoy K; Foster, Lydia D et al. (2016) Association Between CT Angiogram Collaterals and CT Perfusion in the Interventional Management of Stroke III Trial. Stroke 47:535-8
Lees, Kennedy R; Selim, Magdy H; Molina, Carlos A et al. (2016) Early Versus Late Assessment of Stroke Outcome. Stroke 47:1416-9
Vagal, A; Foster, L D; Menon, B et al. (2016) Multimodal CT Imaging: Time to Treatment and Outcomes in the IMS III Trial. AJNR Am J Neuroradiol 37:1393-8
Menon, Bijoy K; Qazi, Emmad; Nambiar, Vivek et al. (2015) Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial. Stroke 46:1239-44
Palesch, Yuko Y; Yeatts, Sharon D; Tomsick, Thomas A et al. (2015) Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial. Stroke 46:1321-7
Tomsick, T A; Foster, L D; Liebeskind, D S et al. (2015) Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial. AJNR Am J Neuroradiol 36:2074-81
Khatri, Pooja; Hacke, Werner; Fiehler, Jens et al. (2015) State of acute endovascular therapy: report from the 12th thrombolysis, thrombectomy, and acute stroke therapy conference. Stroke 46:1727-34
Al-Ali, Firas; Elias, John J; Tomsick, Thomas A et al. (2015) Relative Influence of Capillary Index Score, Revascularization, and Time on Stroke Outcomes From the Interventional Management of Stroke III Trial. Stroke 46:1590-4
Sajobi, Tolulope T; Zhang, Yukun; Menon, Bijoy K et al. (2015) Effect Size Estimates for the ESCAPE Trial: Proportional Odds Regression Versus Other Statistical Methods. Stroke 46:1800-5
Adeoye, Opeolu; Sucharew, Heidi; Khoury, Jane et al. (2015) Recombinant tissue-type plasminogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alone in acute ischemic stroke: propensity score-matched post hoc analysis. Stroke 46:461-4

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