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(Stroke. 2008;39:1389.)
© 2008 American Heart Association, Inc.

Emerging Therapies

A Critique of SAINT II

Wishful Thinking, Dashed Hopes, and the Future of Neuroprotection for Acute Stroke

From the Department of Neurology (S.I.S.), University of Texas Houston Medical School, Houston, Texas; and the Department of Neurology (W.-R.S.), University of Münster, Münster, Germany.

Correspondence to Wolf-Rüdiger Schäbitz, Department of Neurology, University of Münster, Albert-Schweitzer-Str. 33, 48149 Münster, Germany. E-mail schabitz@uni-muenster.de; or Sean I. Savitz, Department of Neurology, University of Texas, Houston Medical School, 6431 Fannin St, Houston, Texas. E-mail sean.i.savitz@uth.tmc.edu

Marc Fisher MD Kennedy Lees MD Section Editors:

Key Words: acute stroke • neuroprotection

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The neutral results of the SAINT II study¹ dashed the hopes for a second ischemic stroke drug in the near future. Although this is certainly disappointing for stroke neurologists, a careful analysis of the NXY-059 development program reveals several deficiencies, which if properly addressed, might revitalize and strengthen the field of neuroprotection for acute ischemic stroke. This critique points out several potential reasons for the failure of SAINT II to replicate the positive findings of SAINT 1,² discusses the preclinical problems with NXY-059, and provides a perspective on the development of future neuroprotective agents for acute ischemic stroke.

	Clinical Trial Problems

 
The SAINT II trial¹ investigated the efficacy of the free-radical–trapping agent, NXY-059, for the treatment of acute ischemic stroke and failed to confirm the positive results of SAINT I.² In the latter study with 1699 patients, NXY-059 showed for the first time in a large phase III trial that a drug other than tissue plasminogen activator (t-PA) might lead to significant improvement on the modified Rankin Scale (mRS) using a novel and controversial outcome analysis (Rankin shift analysis). The larger SAINT II trial with 3306 patients not only failed to replicate improvement on the same primary end point but all secondary end points (neurological deficits on the National Institutes of Health Stroke Scale (NIHSS) at 90 days and activities of daily living on the Barthel Index at 90 days) were identical between treatment groups. Besides the obvious possibility that the drug itself was inactive, which may be considered due to the known . . . [Full Text of this Article]

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