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 f actor receptor antagonist BB-882 in the treatment of patients with sepsis. Design: Double-blind, placebo-controlled, randomized, multicentered study. Setting: Thirty-four European intensive care units. Patients: One hundred fifty-two patients with clinical suspicion of infecti on and a mean APACHE II score between 15 and 35 in the 24 hrs before entry into the trial. Interventions: Patients received either a loading dose of 4 mg of BB-882 an the first day, followed by an intravenous infusion of 96 mg/24 hrs far up to 120 hrs, or placebo. Measurements: Hemodynamic, respiratory and oxygen transport variables, bloo d lactate concentrations, interleukin-6, interleukin-8, tumor necrosis fact or (TNF)-alpha, soluble TNF receptor concentrations, organ failure score, 2 8-day mortality rate, Acute Physiology And Chronic Health Evaluation (APACH E) II score within 24 hrs of entry. Results: Sixty-nine patients (42 mate, 27 female) received placebo and 83 ( 59 male, 24 female) received BB-882. Patients ranged in age from 16 to 89 y rs (mean, 60 yrs). No important differences existed between the two groups in terms of gender distribution, age, or initial APACHE II score. Sepsis wa s 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 me dian time to death in the placebo group was 6.0 days, and in the treatment group, it was 4.5 days (p = .30). Conclusion: Treatment of sepsis with the platelet-activating factor antagon ist BB-882 offers no advantage over placebo on survival, hemodynamic status , respiratory function, or organ failure scores.