Administration of an antibody to E-selectin in patients with septic shock

Objectives: To determine the safety and pharmacokinetics of a murine monoclonal antibody to E-selectin in patients with newly developed septic shock. Design: Open-label, prospective, phase II pilot study with escalating doses of the antibody. Setting: Intensive care unit of a 900-bed university hospital. Patients: Nine patients who survived the first 24 hrs of septic shock. Interventions: 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). Measurements and Main Results: CY1787 was well tolerated in ail 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 Pao(2)/F10(2) 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.