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(Stroke. 1996;27:1507-1515.)
© 1996 American Heart Association, Inc.

Articles

Considerations in the Design of Clinical Trials of Neuroprotective Therapy in Acute Stroke

Paul J. Dorman, MRCP Peter A.G. Sandercock, FRCP

the Neurosciences Trials Unit, Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital (Scotland). E-mail pd@skull.dcn.ed.ac.uk.

Correspondence to Dr Paul Dorman, Neurosciences Trials Unit, Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Rd, Edinburgh, Scotland EH4 2XU.

Key Words: clinical trials • neuroprotection • stroke, acute

	Introduction

 
Acute stroke is a substantial public health problem; over the next decade about 15 million patients will suffer acute stroke in Europe and the United States,¹ and approximately 85% of these strokes will be ischemic in origin. Therefore, an effective and widely applicable treatment of acute cerebral ischemia would have an enormous public health impact, but as yet no such treatment has been found.² In addition, there is no effective treatment for the 15% of patients with primary ICH.

The existence of an ischemic penumbra³ (a zone of ischemically threatened but potentially viable tissue in patients with acute ischemic stroke) in the tissue around a primary intracerebral hematoma has raised interest in whether neuronal damage in this zone may be limited by early neuroprotective intervention. Many agents that intervene at one or more points in the pathophysiological cascades initiated by ischemia have been identified^{4 5 6 7} and are currently entering clinical evaluation.

Well-designed RCTs are the most effective and efficient way to evaluate new treatments. Interest in the design, methodology, analysis, and interpretation of RCTs of treatment of acute stroke has increased substantially in the last decade.^{8 9 10} The design of the large simple trials in acute ischemic stroke, the IST¹¹ and the Chinese Acute Stroke Trial, evolved from the large trials of antithrombotic and thrombolytic therapy in acute myocardial infarction.^{12 13} Because neuroprotective agents differ from antithrombotic and thrombolytic agents in their modes of action, pharmacological properties, and profiles of adverse effects,⁴ a number of methodological issues must be considered in the design . . . [Full Text of this Article]

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