The Interventional Management of Stroke (IMS) II Study

Background and Purpose— The purpose of this study was to further investigate the feasibility and safety of a combined intravenous and intra-arterial approach to recanalization for ischemic stroke. Methods— Subjects, ages 18 to 80, with a baseline NIHSS ≥10 had intravenous recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes) within 3 hours of onset. For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro-infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis. Results— The 81 subjects had a median baseline NIHSS score of 19. The median time to initiation of intravenous rt-PA was 142 minutes as compared with 108 minutes for placebo and 90 minutes for rt-PA–treated subjects in the NINDS rt-PA Stroke Trial (P<0.0001). The 3-month mortality in IMS II subjects was 16% as compared with the mortality of placebo (24%) and rt-PA–treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic intracerebral hemorrhage in IMS II subjects (9.9%) was not significantly different than that for rt-PA treated subjects in the NINDS t-PA Stroke Trial (6.6%). IMS II subjects had significantly better outcomes at 3 months than NINDS placebo-treated subjects for all end points (OR ≥2.7) and better outcomes than NINDS rt-PA–treated subjects as measured by the Barthel Index and Global Test Statistic. Conclusions— A randomized trial of standard intravenous rt-PA as compared with a combined intravenous and intra-arterial approach is warranted and has begun.

[1]  J. Saver.  Does the Merci Retriever work? For. , 2006, Stroke.

[2]  Gerhard Schroth,et al.  NIHSS Score and Arteriographic Findings in Acute Ischemic Stroke , 2005, Stroke.

[3]  N L Geller,et al.  Use of a global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke t-PA Stroke Trial. , 1996, Stroke.

[4]  R. Higashida,et al.  Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke , 2003, Stroke.

[5]  Scott Hamilton,et al.  Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials , 2004, The Lancet.

[6]  J. Slattery,et al.  Interobserver agreement for the assessment of handicap in stroke patients. , 1989, Stroke.

[7]  Ims Study Investigators.  Combined Intravenous and Intra-Arterial Recanalization for Acute Ischemic Stroke: The Interventional Management of Stroke Study , 2004, Stroke.

[8]  H. Lutsep,et al.  Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke: Results of the MERCI Trial , 2005, Stroke.

[9]  W. Hacke,et al.  Hemorrhagic Transformation of Ischemic Brain Tissue: Asymptomatic or Symptomatic? , 2001, Stroke.

[10]  T. Hayakawa,et al.  Intravenous Tissue Plasminogen Activator Ameliorates the Outcome of Hyperacute Embolic Stroke , 1993 .

[11]  J. Grotta,et al.  Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. , 1999, Stroke.

[12]  J. Grotta,et al.  NXY-059 for acute ischemic stroke. , 2006, The New England journal of medicine.

[13]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[14]  M. Kaste,et al.  Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II) , 1998, The Lancet.

[15]  Michael D Hill,et al.  Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. , 2004, The New England journal of medicine.

[16]  L. Wechsler.  Does the Merci Retriever work? Against. , 2006, Stroke.

[17]  J. Arenillas,et al.  Thrombolysis-Related Hemorrhagic Infarction: A Marker of Early Reperfusion, Reduced Infarct Size, and Improved Outcome in Patients With Proximal Middle Cerebral Artery Occlusion , 2002, Stroke.

[18]  H. Lutsep.  Thrombolytic and newer mechanical device treatment for acute ischemic stroke , 2006, Expert review of neurotherapeutics.

[19]  K. Lovblad,et al.  Intravenous Versus Combined (Intravenous and Intra-Arterial) Thrombolysis in Acute Ischemic Stroke: A Transcranial Color-Coded Duplex Sonography–Guided Pilot Study , 2006, Stroke.

[20]  P. Lyden,et al.  A Pilot Dose-Escalation Safety Study of Tenecteplase in Acute Ischemic Stroke , 2005, Stroke.

[21]  R. Higashida,et al.  Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial , 1999 .

[22]  S. Warach,et al.  The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): A Phase II MRI-Based 9-Hour Window Acute Stroke Thrombolysis Trial With Intravenous Desmoteplase , 2005, Stroke.