title: Administration of an antibody to E-selectin in patients with septic shock.
abstract: OBJECTIVE
  To determine the safety and pharmacokinetics of a murine monoclonal antibody to E-selectin in patients with newly developed septic shock.
  
  
  METHODS
  Open-label, prospective, phase II pilot study with escalating doses of the antibody.
  
  
  METHODS
  Intensive care unit of a 900-bed university hospital.
  
  
  METHODS
  Nine patients who survived the first 24 hrs of septic shock.
  
  
  METHODS
  In addition to standard therapy, an intravenous bolus of a murine monoclonal antibody to E-selectin, CY1787, was given at doses of 0.1 mg/kg (n = 3), 0.33 mg/kg (n = 3), and 1.0 mg/kg (n = 3).
  
  
  RESULTS
  CY1787 was well tolerated in all patients. Signs of shock resolved in all patients, and organ failure entirely reversed in eight patients. All patients survived the 28-day follow-up. Administration of CY1787 was associated with an early and brisk increase in PaO2/FIO2 ratio (p < .001), from 146 +/- 38 mm Hg (19.5 +/- 5.1 kPa) to 205 +/- 45 mm Hg (27.3 +/- 6.0 kPa) after 2 hrs, and 250 +/- 58 mm Hg (33.3 +/- 7.7 kPa) after 12 hrs. A dose-related effect of CY1787 was suggested by an earlier weaning from catecholamine therapy and a faster resolution of organ failure in the high-dose group. Development of antimouse antibodies was documented in eight patients.
  
  
  CONCLUSIONS
  This pilot study indicates that this antibody to E-selectin appears to be safe and may represent a promising form of therapy in septic shock.
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Friedman
authors.forename: S
authors.initials: S
authors.lastname: Jankowski
authors.forename: M
authors.initials: M
authors.lastname: Shahla
authors.forename: M
authors.initials: M
authors.lastname: Goldman
authors.forename: R M
authors.initials: RM
authors.lastname: Rose
authors.forename: R J
authors.initials: RJ
authors.lastname: Kahn
authors.forename: J L
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001784:Blood Gas Analysis; D019040:E-Selectin / Q000276:immunology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012772:Shock, Septic / Q000276:immunology / Q000628:therapy*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D019040:E-Selectin