TREATMENT OF SEVERE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME AND SEPSIS WITH A NOVEL BRADYKININ ANTAGONIST, DELTIBANT (CP-0127) - RESULTS OFA RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective.-To test the effect of a novel bradykinin antagonist, deltib ant (CP-0127), on survival, organ dysfunction, and other outcomes in p atients with the systemic inflammatory response syndrome (SIRS) and pr esumed sepsis. Design.-Multicenter, randomized, placebo-controlled, do uble-blind, parallel, dose-ranging trial. Follow-up for 28 days or unt il death. Setting.-A total of 47 US referral hospitals. Patients.-A to tal of 504 patients with SIRS and documented evidence of infection plu s 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, Concurr ent therapy at the discretion of the treating physician. Main Outcome Measure.-Risk-adjusted, 28-day, log-normal intent-to-treat survival an alysis. Risk adjustment was performed using a study-specific risk mode l derived from the APACHE III database. Results.-Deltibant had no sign ificant effect on risk-adjusted 28-day survival. In a posthoc analysis , risk-adjusted 7-day survival showed a nonsignificant trend toward im provement (P=.09). The 28-day risk-adjusted survival in the prospectiv ely 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-negat ive sepsis; however, additional studies would be required to prove thi s.