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Article
August 28, 1991

A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis

Richard L. Greenman, MD; Roland M. H. Schein, MD; Michael A. Martin, MD; et al Richard P. Wenzel, MSc, MD; Neil R. Maclntyre, MD; George Emmanuel, MD; Herman Chmel, MD; Richard B. Kohler, MD; Mary McCarthy, MD; Joseph Plouffe, MD; Jane A. Russell, RN; Elena Hollender, MD; Richard Immerman, MD; Michael Pfaller, MD; Carol Sheetz, RN; Peter Jebson, MD; Alison Houston, MT, ASCP; Dawn Rehak, RN; Patricia Empson, RN; Jill Ireland, RRT; Shakti Narain, MD; Jack E. Rashkin, MD; Richard A. Jacobs, MD; Jacqueline Octavio, RN; Rebecca Coleman, PharmD; Vicki S. Kenyon, RN; Bienvenido G. Yangco, MD; John F. Toney, MD; John Edwards, MD; Mark Crislip, MD; Ronald W. Quenzer, MD; Gordon M. Trenholme, MD; Barbara A. Schmitt, RN; Jeffrey E. Grossman, MD; Charles L. Daley, MD; Henry F. Chambers, MD; Paul B. Iannini, MD; Thomas Graziano, MD; Ronald Dandurand, MD; Gary Schieiter, MD; Mark Kunkel, MD; George A. Pankey, MD; Brenda Mayeur, RN; Sandra Abadie-Kemmerly, MD; James Zachery, MD; Michael Meadors, MD; Jeffrey Coco, MD; Charles V. Sanders, MD; W. Lance George, MD; Steven Gardner, MD; Sydney Finegold, MD; Gordon R. Bernard, MD; Paul Bogden, MD; Erlaine Bello, MD; A. Gray Ellrodt, MD; Jan Dauer, MD; Mary S. Riedinger, RN; Burt R. Meyers, MD; Thomas Iberti, MD; J. Peter Rissing, MD; Donald Nelson, MD; Quyen Luu, MD; G. Douglas Campbell, MD; Keith Olsen, PharmD; Alex Carvalho, MD; Arthur E. Brown, MD; Heinz J. Schmitt, MD; Sheldon Brown, MD; Jerome J. Schentag, PharmD; Philip B. Wels, MD; Patricia E. Wing, RN; Lynda S. Welage, PharmD; Richard Quintiliani, MD; P. H. Chandrasekar, MD; Kenneth R. Ratzan, MD; David L. Dunn, MD, PhD; Kenneth Gorelick, MD; Nancy Wedel, MD; Samuel Saks, MD; John Hannigan, MS; Samuel K. Ackerman, MD; Patrick J. Scannon, MD, PhD; David Salsburg, PhD; C. Douglas Webb, PhD
Author Affiliations

Miami (Fla) Veterans Affairs Medical Center and University of Miami.; University of Iowa, Iowa City; Duke University, Durham, NC; Bay Pines Veterans Affairs Medical Center and University of South Florida, Tampa.; University of California, San Francisco, Moffett Hospital.; University of South Florida, Tampa.; University of California, Los Angeles.; University of New Mexico, Albuquerque.; Rush-Presbyterian-St Lukes Medical Center, Chicago, Ill.; University of Wisconsin-Madison; University of California, San Francisco, San Francisco General Hospital; Danbury Hospital; Ochsner Clinic.; Louisiana State University.; Veterans Affairs Medical Center, Los Angeles, Calif.; Vanderbilt University, Nashville, Tenn.; University of Hawaii, Honolulu.; Cedars-Sinai Medical Center.; The Mount Sinai Medical Center, New York, NY.; Medical College of Georgia.; Veterans Affairs Medical Center, Little Rock, Ark.; Memorial Sloan-Kettering Cancer Center.; SUNY at Buffalo and The Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital.; Hartford (Conn) Hospital.; Wayne State University, Detroit.; Mount Sinai Medical Center, Miami, Fla.; University of Minnesota, Minneapolis.; XOMA Corporation, Berkeley, Calif.; Pfizer Inc.
From the Department of Medicine, Miami (Fla) Veterans Affairs Medical Center and University of Miami School of Medicine (Drs Greenman and Schein); Department of Medicine, University of Iowa College of Medicine, Iowa City (Drs Martin and Wenzel); Department of Medicine, Duke University School of Medicine, Durham, NC (Dr Maclntyre); Department of Internal Medicine, Bay Pines Veterans Affairs Medical Center and University of South Florida College of Medicine, Tampa (Drs Emmanuel and Chmel); Departments of Medicine (Dr Kohler) and Surgery (Dr McCarthy), Indiana University School of Medicine, Indianapolis; and Department of Medicine, Ohio State University School of Medicine, Columbus (Dr Plouffe and Ms Russell). Dr Martin is currently with the Department of Medicine, University of Maryland School of Medicine, Baltimore.

Miami (Fla) Veterans Affairs Medical Center and University of Miami.; University of Iowa, Iowa City; Duke University, Durham, NC; Bay Pines Veterans Affairs Medical Center and University of South Florida, Tampa.; University of California, San Francisco, Moffett Hospital.; University of South Florida, Tampa.; University of California, Los Angeles.; University of New Mexico, Albuquerque.; Rush-Presbyterian-St Lukes Medical Center, Chicago, Ill.; University of Wisconsin-Madison; University of California, San Francisco, San Francisco General Hospital; Danbury Hospital; Ochsner Clinic.; Louisiana State University.; Veterans Affairs Medical Center, Los Angeles, Calif.; Vanderbilt University, Nashville, Tenn.; University of Hawaii, Honolulu.; Cedars-Sinai Medical Center.; The Mount Sinai Medical Center, New York, NY.; Medical College of Georgia.; Veterans Affairs Medical Center, Little Rock, Ark.; Memorial Sloan-Kettering Cancer Center.; SUNY at Buffalo and The Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital.; Hartford (Conn) Hospital.; Wayne State University, Detroit.; Mount Sinai Medical Center, Miami, Fla.; University of Minnesota, Minneapolis.; XOMA Corporation, Berkeley, Calif.; Pfizer Inc.
From the Department of Medicine, Miami (Fla) Veterans Affairs Medical Center and University of Miami School of Medicine (Drs Greenman and Schein); Department of Medicine, University of Iowa College of Medicine, Iowa City (Drs Martin and Wenzel); Department of Medicine, Duke University School of Medicine, Durham, NC (Dr Maclntyre); Department of Internal Medicine, Bay Pines Veterans Affairs Medical Center and University of South Florida College of Medicine, Tampa (Drs Emmanuel and Chmel); Departments of Medicine (Dr Kohler) and Surgery (Dr McCarthy), Indiana University School of Medicine, Indianapolis; and Department of Medicine, Ohio State University School of Medicine, Columbus (Dr Plouffe and Ms Russell). Dr Martin is currently with the Department of Medicine, University of Maryland School of Medicine, Baltimore.

JAMA. 1991;266(8):1097-1102. doi:10.1001/jama.1991.03470080067031
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.(JAMA. 1991;266:1097-1102)

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