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

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

doi:10.1001/jama.1991.03470080067031

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

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

Wright State University

Research output: Contribution to journal › Article › peer-review

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

Original language	American English
Journal	JAMA: The Journal of the American Medical Association
Volume	266
DOIs	https://doi.org/10.1001/jama.1991.03470080067031
State	Published - Aug 28 1991

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Medical Specialties
Medicine and Health Sciences
Surgery

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Greenman, R. L., Schein, R. M. H., Martin, M. A., Wenzel, R. P., MacIntyre, N. R., Emmanuel, G., Chmel, H., Kohler, R., McCarthy, M. C., Plouffe, J., Russell, J. A., Hollender, E., Immerman, R., Pfaller, M., Sheetz, C., Jebson, P., Houston, A., Rehak, D., Empson, P., ... Webb, D. (1991). A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis. JAMA: The Journal of the American Medical Association, 266. https://doi.org/10.1001/jama.1991.03470080067031

Greenman, RL, Schein, RMH, Martin, MA, Wenzel, RP, MacIntyre, NR, Emmanuel, G, Chmel, H, Kohler, R, McCarthy, MC, 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, P, 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, D 1991, 'A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis', JAMA: The Journal of the American Medical Association, vol. 266. https://doi.org/10.1001/jama.1991.03470080067031

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

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",

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

year = "1991",

month = aug,

day = "28",

doi = "10.1001/jama.1991.03470080067031",

language = "American English",

volume = "266",

journal = "JAMA: The Journal of the American Medical Association",

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TY - JOUR

T1 - A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis

AU - Greenman, Richard L.

AU - Schein, Roland M.H.

AU - Martin, Michael A.

AU - Wenzel, Richard P.

AU - MacIntyre, Neil R.

AU - Emmanuel, George

AU - Chmel, Herman

AU - Kohler, Richard

AU - McCarthy, Mary C.

AU - Plouffe, Joseph

AU - Russell, Jane A.

AU - Hollender, Elena

AU - Immerman, Richard

AU - Pfaller, Michael

AU - Sheetz, Carol

AU - Jebson, Peter

AU - Houston, Alison

AU - Rehak, Dawn

AU - Empson, Patricia

AU - Ireland, Jill

AU - Narain, Shakti

AU - Rashkin, Jack E.

AU - Jacobs, Richard A.

AU - Octavio, Jacqueline

AU - Coleman, Rebecca

AU - Kenyon, Vicki S.

AU - Yangco, Bienvenido G.

AU - Toney, John F.

AU - Edwards, John

AU - Crislip, Mark

AU - Quenzer, Ronald W.

AU - Trenholme, Gordon M.

AU - Schmitt, Barbara A.

AU - Grossman, Jeffrey E.

AU - Daley, Charles L.

AU - Chambers, Henry F.

AU - Iannini, Paul B.

AU - Graziano, Thomas

AU - Dandurand, Ronald

AU - Schieiter, Gary

AU - Kunkel, Mark

AU - Pankey, George A.

AU - Mayeur, Brenda

AU - Abadie-Kemmerly, Sandra

AU - Zachery, James

AU - Meadors, Michael

AU - Coco, Jeffrey

AU - Sanders, Charles V.

AU - George, W. Lance

AU - Gardner, Steven

AU - Finegold, Sydney

AU - Bernard, Gordon R.

AU - Bogden, Paul

AU - Bello, Erlaine

AU - Ellrodt, A. Gray

AU - Dauer, Jan

AU - Riedinger, Mary S.

AU - Meyers, Burt R.

AU - Iberti, Thomas

AU - Rissing, Peter

AU - Nelson, Donald

AU - Luu, Quyen

AU - Campbell, G. Douglas

AU - Olsen, Keith

AU - Carvalho, Alex

AU - Brown, Arthur E.

AU - Schmitt, Heinz J.

AU - Brown, Sheldon

AU - Schentag, Jerome J.

AU - Wels, Philip B.

AU - Wing, Patricia E.

AU - Welage, Lynda S.

AU - Quintiliani, Richard

AU - Chandrasekar, P. H.

AU - Ratzan, Kenneth R.

AU - Dunn, David L.

AU - Gorelick, Kenneth

AU - Wedel, Nancy

AU - Saks, Samuel

AU - Hannigan, John

AU - Ackerman, Samuel K.

AU - Scannon, Patrick J.

AU - Salsburg, David

AU - Webb, Douglas

PY - 1991/8/28

Y1 - 1991/8/28

N2 - 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

AB - 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

UR - https://corescholar.libraries.wright.edu/surg/546

U2 - 10.1001/jama.1991.03470080067031

DO - 10.1001/jama.1991.03470080067031

M3 - Article

VL - 266

JO - JAMA: The Journal of the American Medical Association

JF - JAMA: The Journal of the American Medical Association

ER -

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

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