Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal Septic Shock Trial Study Group.
Meningococcal septic shock has a rapid onset and characteristic skin hemorrhages that allow bedside diagnosis. Initial plasma endotoxin levels are high and correlate closely with clinical outcome. In a double-blind, randomized, placebo-controlled trial (planned, n = 270; actual, n = 269), we compared the effectiveness of HA-1A (6 mg/kg of body weight iv; maximum, 100 mg), a human monoclonal antibody to endotoxin, and placebo in reducing the 28-day all-cause mortality rate among children with a presumptive clinical diagnosis of meningococcal septic shock. Treatment groups were well balanced for baseline characteristics and prespecified prognostic variables. In this trial no significant benefit of HA-1A could be demonstrated. The 28-day mortality rates in the intention-to-treat analysis were as follows: placebo, 28%; HA-1A, 18%; reduction in mortality, 33% (P = .11, per Fisher's exact test, two-tailed; odds ratio = 0.59; 95% confidence interval for the difference, 0.31-1.05). All patients tolerated HA-1A well, and no antibodies to HA-1A were detected.
Derkx
B
B
Academic Medical Center, University of Amsterdam, Emma Children's Hospital AMC, Department of Pediatrics, The Netherlands. h.h.derkx@amc.uva.nl
Wittes
J
J
McCloskey
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004731:Endotoxins / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D009345:Neisseria meningitidis / Q000302:isolation & purification; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004731:Endotoxins; C068069:nebacumab