Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial.

Abstract

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.

• Authors: Enlimomab Acute Stroke Trial Investigators
• Journal: Neurology (Neurology) Vol. 57 Issue 8 Pg. 1428-34 (Oct 23 2001) ISSN: 0028-3878 [Print] United States
• PMID: 11673584 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Intercellular Adhesion Molecule-1

Topics

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Brain Ischemia (mortality, therapy)
• Disease-Free Survival
• Female
• Humans
• Intercellular Adhesion Molecule-1 (immunology)
• Male
• Middle Aged
• Stroke (mortality, therapy)