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 microg x kg(-1) x 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.