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

Clin Infect Dis. 1999 Apr;28(4):770-7. doi: 10.1086/515184.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Endotoxins / blood
  • Endotoxins / immunology*
  • Female
  • Humans
  • Infant
  • Male
  • Meningococcal Infections / drug therapy*
  • Meningococcal Infections / microbiology
  • Meningococcal Infections / mortality
  • Neisseria meningitidis / isolation & purification
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Endotoxins
  • nebacumab