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.
RCT Entities:
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.
Authors: Sara H Bengtson; Caroline Sandén; Matthias Mörgelin; Pauline F Marx; Anders I Olin; L M Fredrik Leeb-Lundberg; Joost C M Meijers; Heiko Herwald Journal: J Innate Immun Date: 2008-07-12 Impact factor: 7.349
Authors: Sara H Bengtson; Stephen B Phagoo; Anna Norrby-Teglund; Lisa Påhlman; Matthias Mörgelin; Bruce L Zuraw; L M Fredrik Leeb-Lundberg; Heiko Herwald Journal: Blood Date: 2006-05-30 Impact factor: 22.113