title: Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group.
abstract: OBJECTIVE
  To compare the effectiveness of 100 mg of HA-1A and placebo in reducing the 14-day all-cause mortality rate in patients with septic shock and gram-negative bacteremia in the Centocor: HA-1A Efficacy in Septic Shock (CHESS) trial, and to assess the safety of 100 mg of HA-1A given to patients with septic shock who did not have gram-negative bacteremia.
  
  
  METHODS
  Large, simple, group-sequential, randomized, double-blind, multicenter, placebo-controlled trial.
  
  
  METHODS
  603 investigators at 513 community and university-affiliated hospitals in the United States.
  
  
  METHODS
  Within 6 hours before enrollment, the patients had been in shock with a systolic blood pressure of less than 90 mm Hg after adequate fluid challenge or had received vasopressors to maintain blood pressure. These episodes of shock began within 24 hours of enrollment. A presumptive clinical diagnosis of gram-negative infection as the cause of the shock episode and a commitment from the patients' physicians to provide full supportive care were required.
  
  
  METHODS
  Blood cultures were obtained within 48 hours of enrollment, and death at day 14 after treatment was recorded. Adverse events occurring within 14 days after enrollment were also tabulated.
  
  
  RESULTS
  2199 patients were enrolled; 621 (28.2%) met all enrollment criteria, received HA-1A or placebo, and had confirmed gram-negative bacteremia. Mortality rates in this group were as follows: placebo, 32% (95 and HA-1A, 33% (109 of 328) (P = 0.864, Fisher exact test, two-tailed; 95% CI for the difference, -6.2% to 8.6%). Mortality rates in the patients without gram-negative bacteremia were as follows: placebo, 37% (292 of 793) and HA-1A, 41% (318 of 785) (P = 0.073, Fisher exact test, one-tailed; CI, -0.8% to 8.8%).
  
  
  CONCLUSIONS
  In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria.
authors.affiliation: Centocor, Inc., Malvern, Pennsylvania.
authors.forename: R V
authors.initials: RV
authors.lastname: McCloskey
authors.forename: R C
authors.initials: RC
authors.lastname: Straube
authors.forename: C
authors.initials: C
authors.lastname: Sanders
authors.forename: S M
authors.initials: SM
authors.lastname: Smith
authors.forename: C R
authors.initials: CR
authors.lastname: Smith
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016470:Bacteremia / Q000628:therapy*; D004311:Double-Blind Method; D004731:Endotoxins / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000628:therapy*; D006801:Humans; D009026:Mortality; D011446:Prospective Studies; D012772:Shock, Septic / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004731:Endotoxins; C068069:nebacumab