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

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. Design.-Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death. Setting.-A total of 47 US referral hospitals. Patients.-A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems. Interventions.-Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3, 1.0, or 3.0 mu g . kg(-1). min(-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. 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.