—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.
—Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death.
—A total of 47 US referral hospitals.
—A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems.
—Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3,1.0, or 3.0 μg.kg-1.man-1) of deltibant. Concurrent therapy at the discretion of the treating physician.
Main Outcome Measure.
—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.
—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).
—Deltibant may have some effect on survival in patients with SIRS and gram-negative sepsis; however, additional studies would be required to prove this.