(Stroke. 2000;31:2543.)
© 2000 American Heart Association, Inc.
Original Contributions |
Lubeluzole in Acute Ischemic Stroke Treatment
A Double-Blind Study With an 8-Hour Inclusion Window Comparing a 10-mg Daily Dose of Lubeluzole With Placebo
From the Department of Neurology, University Essen, Germany (H.C.D.); Janssen Research Foundation, Beerse, Belgium (M.C., T.W.); Department of Neurology, University Hospital Rotterdam, the Netherlands (P.J.K.); Department of Neurology, University of Texas, Houston (J.G.); Department of Neurology, University Heidelberg, Germany (W.H.); Department of Clinical Neuroscience, University Helsinki, Finland (M.K.); and Wolfson Unit of Clinical Pharmacology, Newcastle upon Tyne, UK (G.F.).
Correspondence to H.C. Diener, MD, Department of Neurology, University Essen, Hufelandstrasse 55, 45122 Essen, Germany. E-mail h.diener{at}uni-essen.de
Background and Purpose—This trial was a double-blind, placebo-controlled, phase III trial with an 8-hour inclusion window to assess the efficacy and safety of an intravenous loading dose of 7.5 mg followed by a daily intravenous dose of 10 mg lubeluzole for 5 days in acute ischemic stroke patients.
Methods—A total of 1786 patients were randomized: 901 to lubeluzole and 885 to placebo. Overall, 212 patients (23.5%) from the lubeluzole group and 213 (24.1%) from the placebo group discontinued the trial prematurely. In the lubeluzole group 201 patients (22.3%) discontinued because of adverse events compared with 193 patients (21.8%) in the placebo group.
Results—The primary population for the efficacy analysis comprised the core stroke patients (exclusion of older patients aged >75 years with severe stroke) in the 0- to 6-hour inclusion time window. The primary efficacy parameter was a 3-category functional status (Barthel Index 70 to 100/0 to 70/vegetative, dead) at week 12. In the lubeluzole group 207 patients (47.8%) were classified as mildly dependent/independent at week 12, 131 (30.3%) were moderately/severely dependent, and 95 (21.9%) were vegetative/dead. In the placebo group these numbers were 221 (54.4%), 112 (27.6%), and 73 (18.0%), respectively. Logistic regression analysis showed no statistically significant difference between the treatment groups (P=0.162). Additionally, for none of the secondary efficacy parameters (mortality at week 12, modified Rankin score, total Barthel score) was a statistically significant difference between the lubeluzole and placebo groups obtained. There were no statistically significant differences between the 2 treatments for all treated patients, patients included within the 6- to 8-hour window, and patients with severe strokes aged >75 years. Overall, of all treated patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) with placebo. Of all subjects treated, 853 (95%) on lubeluzole and 826 (93%) on placebo reported an adverse event during their treatment period or within the next 2 days after discontinuation of treatment. The most frequently observed adverse events were fever (25.9% lubeluzole; 23.4% placebo), constipation (20.2%; 19.7%), and headache (17.6%; 21.2%). Imbalances were found for atrial fibrillation (1.8% lubeluzole; 1.1% placebo) and QT prolongation (0.9%; 0.2%).
Conclusions—This study failed to show an efficacy of lubeluzole in the treatment of acute stroke. On the other hand, lubeluzole treatment by the current dosage schedule was not associated with a significant safety problem.
Key Words: clinical trials • lubeluzole • neuroprotection • stroke
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