Treatment of Gram-Negative Bacteremia and Septic Shock with HA-1A Human Monoclonal Antibody against Endotoxin

Background. HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia. Methods. To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A(in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol. Results. Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and sho...