Use of anti-ICAM-1 therapy in ischemic stroke
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- 23 October 2001
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 57 (8), 1428-1434
- https://doi.org/10.1212/wnl.57.8.1428
Abstract
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. 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. 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. 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.Keywords
This publication has 21 references indexed in Scilit:
- Anti–Intercellular Adhesion Molecule–1 Antibody Reduces Ischemic Cell Damage After Transient But Not Permanent Middle Cerebral Artery Occlusion in the Wistar RatStroke, 1995
- Spontaneous Middle Cerebral Artery Reperfusion in Ischemic StrokeStroke, 1995
- Leucocyte-endothelial interactions and regulation of leucocyte migrationThe Lancet, 1994
- Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke.Stroke, 1992
- Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons.Stroke, 1991
- Adhesion receptors of the immune systemNature, 1990
- Early Polymorphonuclear Leukocyte Accumulation Correlates with the Development of Posttraumatic Cerebral Edema in RatsJournal of Neurotrauma, 1990
- Measurements of acute cerebral infarction: a clinical examination scale.Stroke, 1989
- Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration.JCI Insight, 1988
- Leukocyte counts and cerebrovascular diseaseJournal of Chronic Diseases, 1982