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The tribulations of stroke trials
  1. Felipe C Albuquerque1,
  2. David Fiorella2,
  3. Joshua A Hirsch3,
  4. Charles Prestigiacomo4,
  5. Robert W Tarr5
  1. 1Division of Neurological Surgery, Barrow Neurological Institute, Phoenix, Arizona, USA
  2. 2Department of Neurosurgery, State University of New York at Stony Brook, Stony Brook, New York, USA
  3. 3NeuroEndovascular Program, Massachusetts General Hospital, Boston, Massachusetts, USA
  4. 4Department of Neurological Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA
  5. 5Department of Radiology, University Hospitals Case Medical Center, Cleveland, Ohio, USA
  1. Correspondence to Dr Felipe C Albuquerque, Division of Neurological Surgery, Barrow Neurological Institute, 2910 N 3rd Ave, Phoenix, AZ 85013, USA; felipe.albuquerque{at}

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In February the New England Journal of Medicine published the long-awaited results of three prospective stroke trials. The Interventional Management of Stroke III (IMS III) trial, the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) trial and the SYNTHESIS Expansion trial all concluded that endovascular therapy (EVT) was not superior to medical management in the treatment of acute stroke.1–3

A critical appraisal of these trials, however, raises serious questions as to their applicability to the contemporary treatment of acute ischemic stroke. In evaluating the results, it is of paramount importance to keep two seemingly obvious fundamental concepts in mind. First, endovascular techniques are not designed to treat all acute ischemic stroke; they are specifically designed to address stroke secondary to large vessel occlusion (LVO). Any clinical trial testing the efficacy of a procedure must be meticulously designed to exclude patients who do not have the index disease process—in this case LVO. Any trial of EVT which includes a significant percentage of patients without the index disease will have little or no capacity to demonstrate a treatment effect. The IMS III and SYNTHESIS Expansion trials both fail in this regard.

Second, in order to evaluate a treatment paradigm within in a clinical trial—in this case EVT—it is a prerequisite that the allocated treatments are actually performed in those subjects randomized to the treatment arm and that the technical success rates achieved by the devices and operators are acceptable within the context of current practice. The IMS III and MR RESCUE trials both fail in this regard. Unfortunately, these basic criteria for clinical trials are sometimes lost in the overriding momentum to report a final definitive conclusion.

IMS III sought to compare the efficacy of combined intravenous tissue plasminogen activator (tPA) administration plus ‘protocol-approved’ EVT with that of …

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  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.

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