Sepsis Drug Fails to Help Patients at Low Risk of Death
WEDNESDAY, Sept. 28 (HealthDay News) -- A drug approved in the United States for treating severe sepsis, an often-fatal blood infection accompanied by acute organ failure, does not benefit patients at low risk of death.
For less severely ill septic patients, drotrecogin alfa (activated) -- the first bioengineered drug therapy for the treatment of sepsis -- appears to be no more effective than a placebo in reducing death. It also poses a serious risk of bleeding and should not be used, an international research team has concluded.
The multi-center trial to test the effects of the drug in low death-risk patients was terminated early when an interim analysis of data showed little chance it would reduce the risk of death.
"Here's a drug that's potentially harmful, that causes increased bleeding episodes in patients, and if there's no evidence of any benefit, really the appropriate thing to do is to stop the study," explained lead author Dr. Edward Abraham, co-head of the division of pulmonary sciences and critical care medicine at the University of Colorado Health Sciences Center in Denver.
The findings appear in the Sept. 29 issue of the New England Journal of Medicine.
Severe sepsis kills 215,000 people in the United States each year, according to the Society of Critical Care Medicine. It often develops from infections associated with pneumonia, trauma, surgery, burns, or cancer, and can cause clotting and inflammation in the blood vessels.
Drotrecogin alfa (activated) is a genetically engineered version of the activated protein C, a naturally occurring substance that regulates blood clotting, controls inflammation, and helps break down clots, the society explained.
Sold under the brand name Xigris, Eli Lilly and Co.'s sepsis treatment has been the focus of intense scrutiny since the U.S. Food and Drug Administration approved it in November 2001, despite an FDA advisory panel's split decision on whether or not to recommend approval.
As part of its decision, the FDA required Lilly to conduct a number of additional trials, including this current study of adult patients with severe sepsis who were at low risk of death.
Patients were randomly assigned to receive either an intravenous infusion of a placebo or the sepsis drug for 96 hours. Neither clinicians nor patients knew which treatment an individual would receive.
Investigators originally intended to enroll 11,444 patients in the study. At the time of the study's termination, only 2,640 were enrolled. Researchers collected data for 2,613 patients, roughly split between the placebo and sepsis treatment groups.
Based on that data, researchers found no statistically significant differences between the two groups in either hospital deaths or deaths 28 days after the start of infusion therapy.
The rate of serious bleeding, though, was greater in the treatment group than the placebo group during both the infusion and the 28-day study period.
"So, I think the overall message of this study is that one should not use this drug in less severely ill septic patients," Abraham said.
In light of the new findings, Dr. Joseph E. Parrillo, head of cardiovascular disease and critical care medicine at Cooper Health System in Camden, N.J., concluded in an accompanying editorial that the FDA made the right call when it approved the drug.
Infectious disease specialist Dr. Richard Wenzel, chairman of the department of internal medicine at Virginia Commonwealth University in Richmond, said the study also confirms the appropriateness of the FDA's decision to limit the drug's approval to only high-risk patients.
"My own interim conclusion is that the drug should be reserved for patients with septic shock criteria and organ failure, should be given by experts in the ICU, given very early in the course of disease, and withheld from patients with risks of bleeding or who are recently recovering from surgery," he said.
That leaves a gap in therapeutic options for patients with severe sepsis, even among people at high risk of death, Abraham noted.
"There is a need for additional drugs for this population -- both the less severely ill and the more severely ill," he said. "Because even with this drug in the more severely ill, there's still a substantial percentage of the patients who die."
The Society of Critical Care Medicine can tell you more about how sepsis is treated.