Scientific paper
Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis

Presented in part at the 32nd Annual Critical Care Congress of the Society of Critical Care Medicine, San Antonio, Texas, January 31, 2003
https://doi.org/10.1016/j.amjsurg.2004.06.008Get rights and content

Abstract

Background

The Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial examined the safety and efficacy of drotrecogin alfa (activated) (Xigris) in adult patients with severe sepsis. A clinical evaluation committee examined clinical data for each patient enrolled in PROWESS. However, there were no surgeons on the committee, and thus questions remained regarding the safety and efficacy of drotrecogin alfa (activated) in surgical patients.

Methods

Masked to treatment, a Surgical Evaluation Committee adjudicated the presence and type of operation, timing of surgery, infection, and adequacy of source control of surgical patients included in PROWESS.

Results

Twenty-eight percent of PROWESS cases were confirmed as surgical. The absolute risk reduction for mortality in all surgical patients was 3.2% and 9.1% for patients undergoing intraabdominal procedures. Serious bleeding during the infusion and 28-day period was similar between surgical and nonsurgical patients.

Conclusions

Consistent with the overall PROWESS results, drotrecogin alfa (activated) has a favorable benefit/risk profile in surgical patients.

Section snippets

Methods

The PROWESS trial was a randomized, placebo-controlled trial that assessed efficacy and safety of drotrecogin alfa (activated) treatment for severe sepsis [13]. In the PROWESS investigation, details of which have been published previously, 850 patients were randomly assigned to drotrecogin alfa (activated) at 24 μg/kg per hour for 96 total hours and 840 patients were randomly assigned to placebo infusion in addition to best supportive care. Patients were eligible for the controlled trial if

Results

A total of 532 (31.5%) of the 1,690 patients enrolled in PROWESS met the initial selection criteria for adjudication by the SEC. The SEC confirmed that 474 of these patients had a protocol-defining operation and thus were considered the surgical cohort for the purpose of this study. Fifty-eight patients did not meet the criteria for inclusion in the surgical cohort. In 36 patients an operative procedure was not performed within the 30 days before meeting criteria for enrollment in PROWESS. In

Comments

We have concluded that 28% of the previously reported PROWESS study population were surgical patients who underwent an operative procedure within the 30-day period prior to study entry. Approximately two thirds of the surgical patients in this study had an intraabdominal operation, with substantially fewer patients having other types of surgery. There was an even distribution between preoperative and postoperative severe sepsis. Consistent with the overall PROWESS trial results, the 28-day

Acknowledgements

This study was supported by Eli Lilly and Company, Indianapolis, Indiana.

In addition to Drs. Barie, Lowry, and Fry, the following participated in the Surgical Evaluation Committee: Samir Awad, M.D., Department of Surgery, Baylor College of Medicine, Houston, TX; Gregory Beilman, M.D., Departments of Surgery and Anesthesia, University of Minnesota, Minneapolis, MN; William Cheadle, M.D., Department of Surgery, University of Louisville and VAMC, Louisville, KY; Mitchell Fink, M.D., Division of

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