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Interventional Management of Stroke III Trial: establishing the foundation
  1. Osama O Zaidat1,2,3,
  2. Marc A Lazzaro1,
  3. Rishi Gupta4,
  4. Dileep R Yavagal5,
  5. Peter A Rasmussen6,
  6. Joshua A Hirsch7,
  7. Alicia C Castonguay1,
  8. Robert W Tarr8
  1. 1Neurointerventional Division, Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  2. 2Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  3. 3Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  4. 4Department of Neurology, Neurosurgery & Radiology, Emory University School of Medicine, Atlanta, Georgia, USA
  5. 5Department of Neurology and Neurosurgery, University of Miami, Miami, Florida, USA
  6. 6Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA
  7. 7NeuroEndovascular Program, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
  8. 8Department of Radiology, University Hospitals Case Medical Center, Ohio, USA
  1. Correspondence to Dr Osama Zaidat, Professor of Neurology, Neurosurgery and Radiology, Medical College of Wisconsin, Froedtert Hospital, Milwaukee, WI 53226, USA; szaidat{at}

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In the wake of the Interventional Management of Stroke (IMS) III independent data safety monitoring board's recommendation on 18 April 2012 to place the IMS III trial on hold due to prespecified planned interim analysis showing the very low likelihood of finding a significant difference between the two treatment arms, one might properly wonder, “What is next”?

Restoration of blood flow after acute ischemic stroke (AIS) is associated with improved outcome and reduced mortality.1 2 Death and disability from AIS remains staggering despite the approval of intravenous thrombolysis with tissue plasminogen activator (IV-rtPA) over 15 years ago. The small population that benefits from IV-rtPA is, in part, limited to those patients treated within a narrow time window. Although cerebrovascular imaging is not consistently performed prior to administration of IV-rTPA, there is some evidence that the infusion is most effective in those patients who have small or distal vessel occlusions.3 The likelihood of recanalization with IV-rtPA declines considerably in occlusions of larger vessels such as the proximal middle cerebral artery and terminal internal carotid artery,3 and underscores the need for good AIS revascularization therapy (RT).

The IMS I trial suggested that combination therapy with IV-rtPA and an intra-arterial (IA) approach was safe and may be clinically useful in AIS treatment.4 This was further supported by the IMS II trial, a single-arm pilot study showing preliminary estimates of efficacy and safety of combination IV and IA therapy.5 The IMS III trial subsequently became the pioneering phase III randomized multicenter open-label clinical trial that was designed to assess if the combined IV-rtPA and IA approach is superior to IV rt-PA alone when initiated within 3 h of AIS onset ( The randomization scheme was to enrol two-thirds in the combined arm and one-third in the IV-rtPA alone arm. …

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  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.