From the National Cardiovascular Center, Osaka (T.Y.); Fuji Brain
Institute Hospital, Shizuoka (K.S.); Tokyo Women's Medical College,
Tokyo (K.T.); Kyorin University, School of Medicine, Tokyo (I.S.); Tokai
University, School of Medicine, Kanagawa (Y.S.); Saitama Medical Center
School, Saitama (T.A.); and Showa University, School of Medicine, Tokyo (H.Y.)
(Japan).
Correspondence to Takenori Yamaguchi, MD, Cerebrovascular Division, National Cardiovascular Center, 5–7-1, Fujishirodai, Suita-shi, Osaka 565, Japan.
Background and Purpose—The
effect of ebselen, a seleno-organic compound with antioxidant activity
through a glutathione peroxidase–like action, on the outcome of acute
ischemic stroke was evaluated in a multicenter,
placebo-controlled, double-blind clinical trial.
Methods—Patients diagnosed as having acute ischemic
stroke who could receive drug treatment within 48 hours of stroke onset
were enrolled. Oral administration of ebselen granules suspended in
water (150 mg BID) or placebo was started immediately after admission
and was continued for 2 weeks. The major end points were the Glasgow
Outcome Scale scores at 1 month and 3 months after the start of
treatment. The modified Mathew Scale and modified Barthel Index scores
at 1 month and 3 months were also studied as secondary outcome
measures.
Results—Three hundred two patients were enrolled in the
trial. Intent-to-treat analysis of 300 patients (151 given
ebselen and 149 given placebo) revealed that ebselen treatment achieved
a significantly better outcome than placebo at 1 month
(P=.023, Wilcoxon rank sum test) but not at 3
months (P=.056, Wilcoxon rank sum test). The
improvement was significant in patients who started ebselen within 24
hours of stroke onset but not in those who started treatment after 24
hours. There was a corresponding improvement in the modified Mathew
Scale and modified Barthel Index scores.
Conclusions—Early treatment with ebselen improved the
outcome of acute ischemic stroke. Ebselen may be a promising
neuroprotective agent.
© 1998 American Heart Association, Inc.
Original Contributions
Ebselen in Acute Ischemic Stroke
A Placebo-Controlled, Double-blind Clinical Trial
Key Words: clinical trials • neuroprotection • stroke outcome
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