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(Stroke. 2009;40:1545.)
© 2009 American Heart Association, Inc.

Controversies in Stroke

The Ethics of Thrombolytic Trials Beyond 3 (or 4.5) Hours

Randomized Controlled Trials Are Required to Change Clinical Practice

From Royal Melbourne Hospital, University of Melbourne, Parkville Vic Australia.

Correspondence to Stephen Davis and Geoffrey Donnan, Controversies Editors, Stroke, Royal Melbourne Hospital, University of Melbourne, Parkville Vic Australia 3050. E-mail stephen.davis@mh.org.au or gdonnan@unimelb.edu.au

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

For several decades, clinicians across all fields of internal medicine have embraced the concept of practice guidelines based on levels of evidence. Medical practice in our careers has been transformed from opinion-driven behavior to a reliance on carefully assessed evidence, ranked according to its strength. Ultimately, we expect level 1 evidence for any new therapy, namely adequately powered and conducted randomized, prospective clinical trials. This has facilitated a universal benchmark for clinical practice throughout the world, with only minor regional variations. In acute stroke, this has led to the recommended use of intravenous tissue plasminogen activator within 3 hours, aspirin within 48 hours, management in stroke care units, and, more recently, hemicraniectomy in selected cases of malignant cerebral edema.¹

How, then, does this principle apply to the current controversy concerning the ethics of using a placebo arm in reperfusion trials in the 3- to 6-hour time window. In other words, the essence of the debate relates to the conduct of clinical trials—not to the clinical decision in an individual patient, in which the physician is aware that level 1 evidence may not yet be available to inform a clinical decision. Until recently, there had been no level 1 evidence in the form of a randomized controlled trial with primary clinical outcome measures for intravenous tissue plasminogen activator (or indeed clot retrieval) beyond 3 hours. Since the preparation of this Controversy, the positive results of the ECASS 3 trial have been published, extending the time window to 4.5 hours for intravenous . . . [Full Text of this Article]

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