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
- Alan M. Fein, MD;
- Gordon R. Bernard, MD;
- Gerard J. Criner, MD;
- Eugene C. Fletcher, MD;
- James T. Good, Jr, MD;
- William A. Knaus, MD;
- Howard Levy, MD;
- George M. Matuschak, MD;
- Harvey M. Shanies, PhD, MD;
- Robert W. Taylor, Jr, MD;
- Timothy C. Rodell, MD
- for the CP-0127 SIRS and Sepsis Study Group
- From the Winthrop-University Hospital, Mineola, NY (Dr Fein); Vanderbilt University, Nashville, Tenn (Dr Bernard); Temple University Hospital, Philadelphia, Pa (Dr Criner); Houston Veterans Affairs Medical Center, Houston, Tex (Dr Fletcher); University of Louisville Hospital and the Louisville Veterans Affairs Medical Center, Louisville, Ky (Dr Fletcher); Porter and Swedish Hospitals, Denver, Colo (Dr Good); George Washington University, Washington, DC (Dr Knaus); University of New Mexico, Albuquerque (Dr Levy); Saint Louis University Medical Center, St Louis, Mo (Dr Matuschak); Elmhurst Hospital Center, Elmhurst, NY (Dr Shanies); St John's Mercy Medical Center, St Louis, Mo; (Dr Taylor); and Cortech, Inc, Denver, Colo (Dr Rodell).
Abstract
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 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.
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.
Footnotes
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A complete list of the members of the CP-0127 SIRS and Sepsis Study Group appears at the end of this article.
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Dr Rodell was an employee of and continues to be a shareholder in and consultant to Cortech, Inc, Denver, Colo, the inventor and owner of deltibant. Dr Knaus is a director and shareholder in APACHE Medical Systems, Washington, DC, which had a contract from Cortech, Inc, for risk model development and analysis of trial data. Dr Bernard has received compensation for consulting services from Cortech, Inc.
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Reprints: Alan M. Fein, MD, Winthrop-University Hospital, 222 Station Plaza N, Mineola, NY 11501.
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Concepts in Emergency and Critical Care section editor:Roger C. Bone, MD, Consulting Editor, JAMA.
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Advisory Panel: Bart Chernow, MD, Baltimore, Md; David Dantzker, MD, New Hyde Park, NY; Jerrold Leiken, MD, Chicago, III; Joseph E. Parrillo, MD, Chicago, III; William J. Sibbald, MD, London, Ontario; and Jean-Louis Vincent, MD, PhD, Brussels, Belgium.
