(Stroke. 2000;31:347.)
© 2000 American Heart Association, Inc.
Original Contributions |
Selfotel in Acute Ischemic Stroke
Possible Neurotoxic Effects of an NMDA Antagonist
From the Departments of Neurology, Royal Melbourne Hospital and University of Melbourne (Australia) (S.M.D.); University of Glasgow (Scotland) (K.R.L.); Stanford University Medical Center, Stanford, Calif (G.W.A.); University of Essen (Germany) (H.C.D.); Novartis Pharma AG (S.M., G.K.); and the University of Toronto, (Canada) (J.N.).
Correspondence and reprint requests to Prof Stephen Davis, Director of Neurology, Melbourne Neuroscience Centre, The Royal Melbourne Hospital, Parkville, Victoria, Australia 3050. E-mail sdavis{at}ariel.its.unimelb.edu.au
Background and Purpose—Based on neuroprotective efficacy in animal models, we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies.
Methods—Two pivotal phase 3 ischemic stroke trials tested
the hypothesis, by double-blind, randomized, placebo-controlled
parallel design, that a single intravenous 1.5 mg/kg dose
of Selfotel, administered within 6 hours of stroke onset, would improve
functional outcome at 90 days, defined as the proportion of patients
achieving a Barthel Index score of 
60. The trials were performed in
patients aged 40 to 85 years with acute ischemic hemispheric
stroke and a motor deficit.
Results—The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients. The groups were well matched for initial stroke severity and time from stroke onset to therapy. There was no difference in the 90-day mortality rate, with 62 deaths (22%) in the Selfotel group and 49 (17%) in the placebo-treated group (RR=1.3; 95% CI 0.92 to 1.83; P=0.15). However, early mortality was higher in the Selfotel-treated patients (day 30: 54 of 280 versus 37 of 286; P=0.05). In patients with severe stroke, mortality imbalance was significant throughout the trial (P=0.05).
Conclusions—Selfotel was not an effective treatment for acute ischemic stroke. Furthermore, a trend toward increased mortality, particularly within the first 30 days and in patients with severe stroke, suggests that the drug might have a neurotoxic effect in brain ischemia.
Key Words: controlled clinical trials • neuroprotection • stroke, acute • stroke, ischemic
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