A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.
OBJECTIVE
To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis.


METHODS
Double-blind, randomized, placebo-controlled trial.


METHODS
Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals.


METHODS
Hospitalized adults with signs of gram-negative infection and a systemic septic response.


METHODS
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.


METHODS
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.
Greenman
R L
RL
Department of Medicine, Miami (Fla) Veterans Affairs Medical Center.
Schein
R M
RM
Martin
M A
MA
Wenzel
R P
RP
MacIntyre
N R
NR
Emmanuel
G
G
Chmel
H
H
Kohler
R B
RB
McCarthy
M
M
Plouffe
J
J
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002985:Clinical Protocols; D004311:Double-Blind Method; D004731:Endotoxins / Q000276:immunology*; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000401:mortality / Q000517:prevention & control; D011446:Prospective Studies; D018805:Sepsis / Q000401:mortality / Q000628:therapy*; D012772:Shock, Septic / Q000401:mortality / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007075:Immunoglobulin M