With technological assistance, approaches to acute stroke trials may be improved. Dose selection, eligibility criteria, control of confounding factors and endpoints can each be optimised. Adaptive randomisation techniques and Bayesian approaches can assist not only dose selection, but also balance of prognostic factors between treatment groups. Magnetic resonance imaging can facilitate enrichment of the trial population with potential responders. Utilisation of existing trial databases can enhance statistical approaches to outcome assessment. Confounding imbalance may also be limited by controlling or adjusting for concomitant conditions and their management. Recent trials have not yet identified a neuroprotectant, but have greatly assisted the prospects of success.

Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333:1581–1587.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH, et al: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study. JAMA 1995;274:1017–1025.
Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P: Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352:1245–1251.
De Keyser J, Sulter G, Luiten PG: Clinical trials with neuroprotective drugs in acute ischaemic stroke: Are we doing the right thing? Trends Neurosci 1999;22:535–540.
Stroke Therapy Academic Industry Roundtable (STAIR). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999;30:2752–2758.
Malakoff D: Bayes offers a ‘new’ way to make sense of numbers. Science 1999;286:1460–1464.
Wahlgren NG, Ranasinha KW, Rosolacci T, Franke CL, van Erven PM, Ashwood T, Claesson L: Clomethiazole Acute Stroke Study (CLASS): Results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 1999;30:21–28.
Dewar D, Yam P, McCulloch J: Drug development for stroke: Importance of protecting cerebral white matter. Eur J Pharmacol 1999;375:41–50.
Baron J: Mapping the ischaemic penumbra with PET: Implications for acute stroke treatment. Cerebrovasc Dis 1999;9:193–201.
Zivin JA: Factors determining the therapeutic window for stroke. Neurology 1998;50:599–603.
Muir KW, Grosset DG: Neuroprotection for acute stroke: Making clinical trials work. Stroke 1999;30:180–182.
Lees KR: Thrombolysis. Br Med Bull 2000;56:389–400.
Lees KR, Asplund K, Carolei A, et al: Glycine antagonist (gavestinel) in neuroprotection (GAIN International): A randomised controlled trial in patients with acute stroke. Lancet 2000;355:1949–1954.
Warach S, Boska M, Welch KMA: Pitfalls and potential of clinical diffusion-weighted MR imaging in acute stroke. Stroke 1997;28:481–482.
Warach S, for the GAIN Americas and GAIN International MRI Investigators: Recruitment in diffusion and perfusion MRI-based stroke drug trials: The GAIN MRI substudy (abstract). Annual Meeting of the American Society of Neuroradiology, Atlanta, April 2–8, 2000.
IMAGES Study Group. IMAGES – Intravenous Magnesium Efficacy in Stroke Trial (abstract). Cerebrovasc Dis 1998;8:86.
Wahlgren NG, MacMahon DG, De Keyser J, Indredavik B, Ryman T: Intravenous Nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischaemic stroke. Cerebrovasc Dis 1994;4:204–210.
Weir CJ, Murray GD, Dyker AG, Lees KR: Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study. BMJ 1997;314:1303–1306.
Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, Meissner I, Murphy D, LaRue L: Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke: Results of a phase Ila randomized trial. Stroke 1995;26:602–605.
Lees KR, Lavelle JF, Cunha L, et al: Glycine antagonist (GV150526) in acute stroke: A double-blind placebo-controlled phase II trial. Cerebrovasc Dis 2001, in press.
Weir CJ, Lees KR: Value of minimisation for treatment allocation in acute stroke trials (abstract). Cerebrovasc Dis 1998;8:32.
Weir CJ, Lees KR: Power of treatment allocation by adaptive stratification in an acute stroke trial (abstract). Cerebrovasc Dis 1999;9:114.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.