title: Treatment of severe systemic inflammatory response syndrome and sepsis with a novel bradykinin antagonist, deltibant (CP-0127). Results of a randomized, double-blind, placebo-controlled trial. CP-0127 SIRS and Sepsis Study Group.
abstract: OBJECTIVE
  To test the effect of a novel bradykinin antagonist, deltibant (CP-0127), on survival, organ dysfunction, and other outcomes in patients with the systemic inflammatory response syndrome (SIRS) and presumed sepsis.
  
  
  METHODS
  Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death.
  
  
  METHODS
  A total of 47 US referral hospitals.
  
  
  METHODS
  A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems.
  
  
  METHODS
  Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3, 1.0, or 3.0 microg x kg(-1) x min(-1)) of deltibant. Concurrent therapy at the discretion of the treating physician.
  
  
  METHODS
  Risk-adjusted, 28-day, log-normal intent-to-treat survival analysis. Risk adjustment was performed using a study-specific risk model derived from the APACHE III database.
  
  
  RESULTS
  Deltibant had no significant effect on risk-adjusted 28-day survival. In a posthoc analysis, risk-adjusted 7-day survival showed a nonsignificant trend toward improvement (P=.09). The 28-day risk-adjusted survival in the prospectively defined subset of patients with gram-negative infections showed a statistically significant improvement (P=.005).
  
  
  CONCLUSIONS
  Deltibant may have some effect on survival in patients with SIRS and gram-negative sepsis; however, additional studies would be required to prove this.
authors.affiliation: Winthrop-University Hospital, Mineola, NY 11501, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Fein
authors.forename: G R
authors.initials: GR
authors.lastname: Bernard
authors.forename: G J
authors.initials: GJ
authors.lastname: Criner
authors.forename: E C
authors.initials: EC
authors.lastname: Fletcher
authors.forename: J T
authors.initials: JT
authors.lastname: Good
authors.forename: W A
authors.initials: WA
authors.lastname: Knaus
authors.forename: H
authors.initials: H
authors.lastname: Levy
authors.forename: G M
authors.initials: GM
authors.lastname: Matuschak
authors.forename: H M
authors.initials: HM
authors.lastname: Shanies
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: T C
authors.initials: TC
authors.lastname: Rodell
mesh_terms: D018806:APACHE; D065168:Bradykinin Receptor Antagonists; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007022:Hypotension / Q000209:etiology; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy / Q000503:physiopathology; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D065168:Bradykinin Receptor Antagonists; D010455:Peptides; C071326:deltibant