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.
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.
Fein
A M
AM
Winthrop-University Hospital, Mineola, NY 11501, USA.
Bernard
G R
GR
Criner
G J
GJ
Fletcher
E C
EC
Good
J T
JT
Knaus
W A
WA
Levy
H
H
Matuschak
G M
GM
Shanies
H M
HM
Taylor
R W
RW
Rodell
T C
TC
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
D065168:Bradykinin Receptor Antagonists; D010455:Peptides; C071326:deltibant