title: A phase II, double-blind, placebo-controlled, ascending-dose study of Eritoran (E5564), a lipid A antagonist, in patients undergoing cardiac surgery with cardiopulmonary bypass.
abstract: BACKGROUND
  Lipid A, the toxic moiety of endotoxin, is linked to multiple complications after cardiac surgery, including fever, vasodilation, and pulmonary and renal dysfunction. The lipid A antagonist eritoran (or E5564) prevents endotoxin-induced systemic inflammation in animals and humans. In this study we assessed the safety of eritoran administration in patients undergoing cardiac surgery and obtained preliminary efficacy data for the prophylaxis of endotoxin-mediated surgical complications.
  
  
  METHODS
  A double-blind, randomized, ascending-dose, placebo-controlled study was conducted at nine hospitals. Patients undergoing coronary artery bypass graft and/or cardiac valvular surgery with cardiopulmonary bypass were enrolled. Patients received a 4-h infusion of placebo (n = 78) vs 2 mg (n = 24), 12 mg (n = 26), or 28 mg (n = 24) of eritoran initiated approximately 1 h before cardiopulmonary bypass.
  
  
  RESULTS
  No significant safety concerns were identified with continuous safety monitoring, and enrollment continued to the highest prespecified dose (28 mg). No statistically significant differences were observed in most variables related to systemic inflammation or organ dysfunction/injury.
  
  
  CONCLUSIONS
  This Phase II safety study suggests that the administration of the novel lipid A antagonist, eritoran, is not associated with overt toxicity in cardiac surgical patients. Blocking lipid A with eritoran does not appear to confer any clear benefit to elective cardiac surgical patients.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. elliott.bennettguerrero@duke.edu
authors.forename: Elliott
authors.initials: E
authors.lastname: Bennett-Guerrero
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Grocott
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Stierer
authors.forename: Charles W
authors.initials: CW
authors.lastname: Hogue
authors.forename: Albert T
authors.initials: AT
authors.lastname: Cheung
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.forename: Alison A
authors.initials: AA
authors.lastname: Carter
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Rossignol
authors.forename: Charles D
authors.initials: CD
authors.lastname: Collard
mesh_terms: D000368:Aged; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control; D011446:Prospective Studies
chemical_list: C404742:E5564; D008050:Lipid A