Phase II multicenter clinical study of the platelet-activating factor receptor antagonist BB-882 in the treatment of sepsis.
OBJECTIVE
To evaluate the safety and efficacy of the platelet-activating factor receptor antagonist BB-882 in the treatment of patients with sepsis.


METHODS
Double-blind, placebo-controlled, randomized, multi-centered study.


METHODS
Thirty-four European intensive care units.


METHODS
One hundred fifty-two patients with clinical suspicion of infection and a mean APACHE II score between 15 and 35 in the 24 hrs before entry into the trial.


METHODS
Patients received either a loading dose of 4 mg of BB-882 on the first day, followed by an intravenous infusion of 96 mg/24 hrs for up to 120 hrs, or placebo.


METHODS
Hemodynamic, respiratory and oxygen transport variables, blood lactate concentrations, interleukin-6, interleukin-8, tumor necrosis factor (TNF)-alpha, soluble TNF receptor concentrations, organ failure score, 28-day mortality rate, Acute Physiology And Chronic Health Evaluation (APACHE) II score within 24 hrs of entry.


RESULTS
Sixty-nine patients (42 male, 27 female) received placebo and 83 (59 male, 24 female) received BB-882. Patients ranged in age from 16 to 89 yrs (mean, 60 yrs). No important differences existed between the two groups in terms of gender distribution, age, or initial APACHE II score. Sepsis was identified as Gram-positive in 49 patients, Gram-negative in 40, mixed in 37, and unknown in 26. No important differences were shown in hemodynamic, respiratory, or oxygen transport variables between groups during the study. Organ failure scores were similar in the two groups throughout the study. Cytokine concentrations were not significantly different in the two groups. Within 28 days of entering the study, 75 patients died, including 31 (45%) in the placebo group and 44 (53%) in the treatment group, p = .32. The median time to death in the placebo group was 6.0 days, and in the treatment group, it was 4.5 days (p = .30).


CONCLUSIONS
Treatment of sepsis with the platelet-activating factor antagonist BB-882 offers no advantage over placebo on survival, hemodynamic status, respiratory function, or organ failure scores.
Vincent
J L
JL
Department of Intensive Care of Erasme University Hospital, Free University of Brussels, Belgium. jlvincen@ulb.ac.be
Spapen
H
H
Bakker
J
J
Webster
N R
NR
Curtis
L
L
D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010980:Platelet Membrane Glycoproteins / Q000627:therapeutic use*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012129:Respiratory Function Tests; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis
C094498:BB 882; D016207:Cytokines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D019344:Lactic Acid; D007930:Leucine