A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis

Richard L. Greenman, Roland Schein, Michael A. Martin, Richard P. Wenzel, Neil R. Maclntyre, George Emmanuel, Herman Chmel, Richard B. Kohler, Mary McCarthy, Joseph Plouffe, Jane A. Russell

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Abstract

Objective. - To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. Design. - Double-blind, randomized, placebo-controlled trial. Setting. - Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. Patients. - Hospitalized adults with signs of gram-negative infection and a systemic septic response. Intervention. - Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. Main Outcome Measures. - Mortality over the 30-day study period, resolution of organ failures, and safety. Results. - Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n=137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; (P=.01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P=.05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. Conclusions. - Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.

Original languageEnglish
Pages (from-to)1097-1102
Number of pages6
JournalJournal of the American Medical Association
Volume266
Issue number8
StatePublished - Aug 28 1991

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  • Medicine(all)

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Greenman, R. L., Schein, R., Martin, M. A., Wenzel, R. P., Maclntyre, N. R., Emmanuel, G., Chmel, H., Kohler, R. B., McCarthy, M., Plouffe, J., & Russell, J. A. (1991). A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. Journal of the American Medical Association, 266(8), 1097-1102.