—To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis.
—Double-blind, randomized, placebo-controlled trial.
—Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals.
—Hospitalized adults with signs of gram-negative infection and a systemic septic response.
—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.
—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.
—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)
Greenman RL, Schein RMH, Martin MA, Wenzel RP, Maclntyre NR, Emmanuel G, Chmel H, Kohler RB, McCarthy M, Plouffe J, Russell JA, Hollender E, Immerman R, Pfaller M, Sheetz C, Jebson P, Houston A, Rehak D, Empson P, Ireland J, Narain S, Rashkin JE, Jacobs RA, Octavio J, Coleman R, Kenyon VS, Yangco BG, Toney JF, Edwards J, Crislip M, Quenzer RW, Trenholme GM, Schmitt BA, Grossman JE, Daley CL, Chambers HF, Iannini PB, Graziano T, Dandurand R, Schieiter G, Kunkel M, Pankey GA, Mayeur B, Abadie-Kemmerly S, Zachery J, Meadors M, Coco J, Sanders CV, George WL, Gardner S, Finegold S, Bernard GR, Bogden P, Bello E, Ellrodt AG, Dauer J, Riedinger MS, Meyers BR, Iberti T, Rissing JP, Nelson D, Luu Q, Campbell GD, Olsen K, Carvalho A, Brown AE, Schmitt HJ, Brown S, Schentag JJ, Wels PB, Wing PE, Welage LS, Quintiliani R, Chandrasekar PH, Ratzan KR, Dunn DL, Gorelick K, Wedel N, Saks S, Hannigan J, Ackerman SK, Scannon PJ, Salsburg D, Webb CD. A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis. JAMA. 1991;266(8):1097–1102. doi:10.1001/jama.1991.03470080067031