Use of anti-ICAM-1 therapy in ischemic stroke

Results of the enlimomab acute stroke trial

D. Sherman, A. Bes, J. D. Easton, W. Hacke, M. Kaste, S. H. Polmar, J. A. Zivin, W. Clark, D. Schneider, J. Whisnant, C. Fieschi, P. Miller, D. Schoenfeld, J. Street, G. Albers, R. Atkinson, J. Biller, Askiel Bruno, D. Carpenter, T. DeGraba & 57 others P. Driscoll, J. Ellis, Jr Greenlee R., David C Hess, D. R. Horowitz, J. Davenport, C. Hsu, S. Starkman, K. Madden, C. Pettigrew, D. Rosenbaum, J. Schim, G. Tietjen, H. Mansbach, K. Edwards, R. Webb, E. Crisostomo, J. Wilterdrink, J. Rothrock, R. Zweifler, J. Dexter, S. Horowitz, N. Futrell, M. Alter, A. Ferbert, H. Prange, M. Wiersbitzky, T. Büttner, A. Schwartz, O. Busse, J. Klingelhöfer, M. Kaste, T. Erilä, J. Sivenius, K. Sotaniemi, J. Liukkonen, C. Hedman, A. Muuronen, A. Rissanen, V. Larrue, J. M. Blard, J. P. Caussanel, J. R. Feve, T. Moulin, M. H. Mahagne, G. Rancurel, P. Trouillas, M. Weber, L. Thomassen, Rosjø, H. J. Johnsen, L. Kjällman, J. Petersson, G. Ferrari, A. Lagi, A. Mamoli, G. Re

Research output: Contribution to journalArticle

356 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1428-1434
Number of pages7
JournalNeurology
Volume57
Issue number8
DOIs
StatePublished - Oct 23 2001
Externally publishedYes

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Intercellular Adhesion Molecule-1
Stroke
Placebos
Therapeutics
Fever
enlimomab
Reperfusion
Leukocytes
Clinical Trials
Inflammation
Survival
Antibodies
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sherman, D., Bes, A., Easton, J. D., Hacke, W., Kaste, M., Polmar, S. H., ... Re, G. (2001). Use of anti-ICAM-1 therapy in ischemic stroke: Results of the enlimomab acute stroke trial. Neurology, 57(8), 1428-1434. https://doi.org/10.1212/WNL.57.8.1428

Use of anti-ICAM-1 therapy in ischemic stroke : Results of the enlimomab acute stroke trial. / Sherman, D.; Bes, A.; Easton, J. D.; Hacke, W.; Kaste, M.; Polmar, S. H.; Zivin, J. A.; Clark, W.; Schneider, D.; Whisnant, J.; Fieschi, C.; Miller, P.; Schoenfeld, D.; Street, J.; Albers, G.; Atkinson, R.; Biller, J.; Bruno, Askiel; Carpenter, D.; DeGraba, T.; Driscoll, P.; Ellis, J.; Greenlee R., Jr; Hess, David C; Horowitz, D. R.; Davenport, J.; Hsu, C.; Starkman, S.; Madden, K.; Pettigrew, C.; Rosenbaum, D.; Schim, J.; Tietjen, G.; Mansbach, H.; Edwards, K.; Webb, R.; Crisostomo, E.; Wilterdrink, J.; Rothrock, J.; Zweifler, R.; Dexter, J.; Horowitz, S.; Futrell, N.; Alter, M.; Ferbert, A.; Prange, H.; Wiersbitzky, M.; Büttner, T.; Schwartz, A.; Busse, O.; Klingelhöfer, J.; Kaste, M.; Erilä, T.; Sivenius, J.; Sotaniemi, K.; Liukkonen, J.; Hedman, C.; Muuronen, A.; Rissanen, A.; Larrue, V.; Blard, J. M.; Caussanel, J. P.; Feve, J. R.; Moulin, T.; Mahagne, M. H.; Rancurel, G.; Trouillas, P.; Weber, M.; Thomassen, L.; Rosjø; Johnsen, H. J.; Kjällman, L.; Petersson, J.; Ferrari, G.; Lagi, A.; Mamoli, A.; Re, G.

In: Neurology, Vol. 57, No. 8, 23.10.2001, p. 1428-1434.

Research output: Contribution to journalArticle

Sherman, D, Bes, A, Easton, JD, Hacke, W, Kaste, M, Polmar, SH, Zivin, JA, Clark, W, Schneider, D, Whisnant, J, Fieschi, C, Miller, P, Schoenfeld, D, Street, J, Albers, G, Atkinson, R, Biller, J, Bruno, A, Carpenter, D, DeGraba, T, Driscoll, P, Ellis, J, Greenlee R., J, Hess, DC, Horowitz, DR, Davenport, J, Hsu, C, Starkman, S, Madden, K, Pettigrew, C, Rosenbaum, D, Schim, J, Tietjen, G, Mansbach, H, Edwards, K, Webb, R, Crisostomo, E, Wilterdrink, J, Rothrock, J, Zweifler, R, Dexter, J, Horowitz, S, Futrell, N, Alter, M, Ferbert, A, Prange, H, Wiersbitzky, M, Büttner, T, Schwartz, A, Busse, O, Klingelhöfer, J, Kaste, M, Erilä, T, Sivenius, J, Sotaniemi, K, Liukkonen, J, Hedman, C, Muuronen, A, Rissanen, A, Larrue, V, Blard, JM, Caussanel, JP, Feve, JR, Moulin, T, Mahagne, MH, Rancurel, G, Trouillas, P, Weber, M, Thomassen, L, Rosjø, Johnsen, HJ, Kjällman, L, Petersson, J, Ferrari, G, Lagi, A, Mamoli, A & Re, G 2001, 'Use of anti-ICAM-1 therapy in ischemic stroke: Results of the enlimomab acute stroke trial', Neurology, vol. 57, no. 8, pp. 1428-1434. https://doi.org/10.1212/WNL.57.8.1428
Sherman D, Bes A, Easton JD, Hacke W, Kaste M, Polmar SH et al. Use of anti-ICAM-1 therapy in ischemic stroke: Results of the enlimomab acute stroke trial. Neurology. 2001 Oct 23;57(8):1428-1434. https://doi.org/10.1212/WNL.57.8.1428
Sherman, D. ; Bes, A. ; Easton, J. D. ; Hacke, W. ; Kaste, M. ; Polmar, S. H. ; Zivin, J. A. ; Clark, W. ; Schneider, D. ; Whisnant, J. ; Fieschi, C. ; Miller, P. ; Schoenfeld, D. ; Street, J. ; Albers, G. ; Atkinson, R. ; Biller, J. ; Bruno, Askiel ; Carpenter, D. ; DeGraba, T. ; Driscoll, P. ; Ellis, J. ; Greenlee R., Jr ; Hess, David C ; Horowitz, D. R. ; Davenport, J. ; Hsu, C. ; Starkman, S. ; Madden, K. ; Pettigrew, C. ; Rosenbaum, D. ; Schim, J. ; Tietjen, G. ; Mansbach, H. ; Edwards, K. ; Webb, R. ; Crisostomo, E. ; Wilterdrink, J. ; Rothrock, J. ; Zweifler, R. ; Dexter, J. ; Horowitz, S. ; Futrell, N. ; Alter, M. ; Ferbert, A. ; Prange, H. ; Wiersbitzky, M. ; Büttner, T. ; Schwartz, A. ; Busse, O. ; Klingelhöfer, J. ; Kaste, M. ; Erilä, T. ; Sivenius, J. ; Sotaniemi, K. ; Liukkonen, J. ; Hedman, C. ; Muuronen, A. ; Rissanen, A. ; Larrue, V. ; Blard, J. M. ; Caussanel, J. P. ; Feve, J. R. ; Moulin, T. ; Mahagne, M. H. ; Rancurel, G. ; Trouillas, P. ; Weber, M. ; Thomassen, L. ; Rosjø ; Johnsen, H. J. ; Kjällman, L. ; Petersson, J. ; Ferrari, G. ; Lagi, A. ; Mamoli, A. ; Re, G. / Use of anti-ICAM-1 therapy in ischemic stroke : Results of the enlimomab acute stroke trial. In: Neurology. 2001 ; Vol. 57, No. 8. pp. 1428-1434.
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title = "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.",
author = "D. Sherman and A. Bes and Easton, {J. D.} and W. Hacke and M. Kaste and Polmar, {S. H.} and Zivin, {J. A.} and W. Clark and D. Schneider and J. Whisnant and C. Fieschi and P. Miller and D. Schoenfeld and J. Street and G. Albers and R. Atkinson and J. Biller and Askiel Bruno and D. Carpenter and T. DeGraba and P. Driscoll and J. Ellis and {Greenlee R.}, Jr and Hess, {David C} and Horowitz, {D. R.} and J. Davenport and C. Hsu and S. Starkman and K. Madden and C. Pettigrew and D. Rosenbaum and J. Schim and G. Tietjen and H. Mansbach and K. Edwards and R. Webb and E. Crisostomo and J. Wilterdrink and J. Rothrock and R. Zweifler and J. Dexter and S. Horowitz and N. Futrell and M. Alter and A. Ferbert and H. Prange and M. Wiersbitzky and T. B{\"u}ttner and A. Schwartz and O. Busse and J. Klingelh{\"o}fer and M. Kaste and T. Eril{\"a} and J. Sivenius and K. Sotaniemi and J. Liukkonen and C. Hedman and A. Muuronen and A. Rissanen and V. Larrue and Blard, {J. M.} and Caussanel, {J. P.} and Feve, {J. R.} and T. Moulin and Mahagne, {M. H.} and G. Rancurel and P. Trouillas and M. Weber and L. Thomassen and Rosj{\o} and Johnsen, {H. J.} and L. Kj{\"a}llman and J. Petersson and G. Ferrari and A. Lagi and A. Mamoli and G. Re",
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TY - JOUR

T1 - Use of anti-ICAM-1 therapy in ischemic stroke

T2 - Results of the enlimomab acute stroke trial

AU - Sherman, D.

AU - Bes, A.

AU - Easton, J. D.

AU - Hacke, W.

AU - Kaste, M.

AU - Polmar, S. H.

AU - Zivin, J. A.

AU - Clark, W.

AU - Schneider, D.

AU - Whisnant, J.

AU - Fieschi, C.

AU - Miller, P.

AU - Schoenfeld, D.

AU - Street, J.

AU - Albers, G.

AU - Atkinson, R.

AU - Biller, J.

AU - Bruno, Askiel

AU - Carpenter, D.

AU - DeGraba, T.

AU - Driscoll, P.

AU - Ellis, J.

AU - Greenlee R., Jr

AU - Hess, David C

AU - Horowitz, D. R.

AU - Davenport, J.

AU - Hsu, C.

AU - Starkman, S.

AU - Madden, K.

AU - Pettigrew, C.

AU - Rosenbaum, D.

AU - Schim, J.

AU - Tietjen, G.

AU - Mansbach, H.

AU - Edwards, K.

AU - Webb, R.

AU - Crisostomo, E.

AU - Wilterdrink, J.

AU - Rothrock, J.

AU - Zweifler, R.

AU - Dexter, J.

AU - Horowitz, S.

AU - Futrell, N.

AU - Alter, M.

AU - Ferbert, A.

AU - Prange, H.

AU - Wiersbitzky, M.

AU - Büttner, T.

AU - Schwartz, A.

AU - Busse, O.

AU - Klingelhöfer, J.

AU - Kaste, M.

AU - Erilä, T.

AU - Sivenius, J.

AU - Sotaniemi, K.

AU - Liukkonen, J.

AU - Hedman, C.

AU - Muuronen, A.

AU - Rissanen, A.

AU - Larrue, V.

AU - Blard, J. M.

AU - Caussanel, J. P.

AU - Feve, J. R.

AU - Moulin, T.

AU - Mahagne, M. H.

AU - Rancurel, G.

AU - Trouillas, P.

AU - Weber, M.

AU - Thomassen, L.

AU - Rosjø,

AU - Johnsen, H. J.

AU - Kjällman, L.

AU - Petersson, J.

AU - Ferrari, G.

AU - Lagi, A.

AU - Mamoli, A.

AU - Re, G.

PY - 2001/10/23

Y1 - 2001/10/23

N2 - 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.

AB - 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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DO - 10.1212/WNL.57.8.1428

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EP - 1434

JO - Neurology

JF - Neurology

SN - 0028-3878

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