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Neurology 2001;57:1428-1434
© 2001 American Academy of Neurology
Articles

Use of anti-ICAM-1 therapy in ischemic stroke

Results of the Enlimomab Acute Stroke Trial

Enlimomab Acute Stroke Trial Investigators

*See the Appendix on page 1433 for a list of group members.

Address correspondence and reprint requests to Dr. D. Sherman, Department of Medicine, Mail Code 7883, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900; e-mail: sherman{at}uthscsa.edu

Background: — There has been recent interest in the possible role of reperfusion-induced inflammation with neuronal injury after stroke. Enlimomab, a murine intercellular adhesion molecule-1 (ICAM-1) antibody, reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of the current clinical trial was to evaluate the use of enlimomab after ischemic stroke.

Methods: — A total of 625 patients with ischemic stroke were randomized to receive either enlimomab (n = 317) or placebo (n = 308) within 6 hours of stroke onset. Treatment was given over 5 days. Patients were evaluated at baseline and on days 5 and 90 after initiation of treatment; long-term assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Scale; other endpoints included Barthel Index (BI) and NIH Stroke Scale and survival.

Results: — At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outcome or die.

Conclusions: — The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.




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