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Administration of an antibody to E-selectin in patients with septic shock
G Friedman1, S Jankowski, M Shahla
1Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
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 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.