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E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.

Publication ,  Journal Article
Angus, DC; Birmingham, MC; Balk, RA; Scannon, PJ; Collins, D; Kruse, JA; Graham, DR; Dedhia, HV; Homann, S; MacIntyre, N
Published in: JAMA
April 5, 2000

CONTEXT: Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. OBJECTIVE: To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. DESIGN: A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. SETTING: Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. PATIENTS: Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. INTERVENTION: Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). MAIN OUTCOME MEASURES: The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. RESULTS: The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. CONCLUSIONS: Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.

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Published In

JAMA

DOI

ISSN

0098-7484

Publication Date

April 5, 2000

Volume

283

Issue

13

Start / End Page

1723 / 1730

Location

United States

Related Subject Headings

  • Survival Analysis
  • Sepsis
  • Prospective Studies
  • Middle Aged
  • Male
  • Humans
  • Gram-Negative Bacterial Infections
  • General & Internal Medicine
  • Female
  • Double-Blind Method
 

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Angus, D. C., Birmingham, M. C., Balk, R. A., Scannon, P. J., Collins, D., Kruse, J. A., … MacIntyre, N. (2000). E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators. JAMA, 283(13), 1723–1730. https://doi.org/10.1001/jama.283.13.1723
Angus, D. C., M. C. Birmingham, R. A. Balk, P. J. Scannon, D. Collins, J. A. Kruse, D. R. Graham, H. V. Dedhia, S. Homann, and N. MacIntyre. “E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.JAMA 283, no. 13 (April 5, 2000): 1723–30. https://doi.org/10.1001/jama.283.13.1723.
Angus DC, Birmingham MC, Balk RA, Scannon PJ, Collins D, Kruse JA, et al. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators. JAMA. 2000 Apr 5;283(13):1723–30.
Angus, D. C., et al. “E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.JAMA, vol. 283, no. 13, Apr. 2000, pp. 1723–30. Pubmed, doi:10.1001/jama.283.13.1723.
Angus DC, Birmingham MC, Balk RA, Scannon PJ, Collins D, Kruse JA, Graham DR, Dedhia HV, Homann S, MacIntyre N. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators. JAMA. 2000 Apr 5;283(13):1723–1730.
Journal cover image

Published In

JAMA

DOI

ISSN

0098-7484

Publication Date

April 5, 2000

Volume

283

Issue

13

Start / End Page

1723 / 1730

Location

United States

Related Subject Headings

  • Survival Analysis
  • Sepsis
  • Prospective Studies
  • Middle Aged
  • Male
  • Humans
  • Gram-Negative Bacterial Infections
  • General & Internal Medicine
  • Female
  • Double-Blind Method