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

Neurology. 2001 Oct 23;57(8):1428-34. doi: 10.1212/wnl.57.8.1428.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antibodies, Monoclonal
  • Intercellular Adhesion Molecule-1