E5 Murine Monoclonal Antiendotoxin Antibody in Gram-Negative Sepsis: A Randomized Controlled Trial
2000
ContextKnowledge and understanding of gram-negative sepsis have grown over
the past 20 years, but the ability to treat severe sepsis successfully has
not.ObjectiveTo assess the efficacy and safety of E5 in the treatment of patients
with severe gram-negative sepsis.DesignA 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.SettingIntensive care units at university medical centers, Veterans Affairs
medical centers, and community hospitals.PatientsAdults aged 18 years or older, with signs and symptoms consistent with
severe sepsis and documented or probable gram-negative infection.InterventionPatients 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 MeasuresThe 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.ResultsThe 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.ConclusionsDespite 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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
30
References
221
Citations
NaN
KQI