Administration of an antibody to E-selectin in patients with septic shock.
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.
Friedman
G
G
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
Jankowski
S
S
Shahla
M
M
Goldman
M
M
Rose
R M
RM
Kahn
R J
RJ
Vincent
J L
JL
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
D000911:Antibodies, Monoclonal; D019040:E-Selectin