News Release

Sepsis drug fights infection, decreases hospital care over two year study

DAA, or Xigris, is underused, raising questions of age bias in medicine

Peer-Reviewed Publication

Vanderbilt University Medical Center

A study in the July 15 issue of the journal "Clinical Infectious Diseases" shows that people 75 and older who were treated for severe sepsis with the drug drotrecogin alpha activated (DAA) had markedly higher survival rates, spent less time on ventilators and in intensive care units and had no more risk of side effects than their younger counterparts -- patients 65 to 74 -- treated with the same drug.

Unfortunately, the study author, Dr. Wes Ely of Vanderbilt University Medical Center, says the drug is highly underutilized. "Conservatively, I would say that fewer than one in four of the older patients who are candidates for this potentially life-saving drug actually receive it," said Ely, associate professor of allergy, pulmonary and critical care medicine and the director of research for the Geriatric Research Education and Clinical Center (GRECC) for the VA Tennessee Valley Health Care System.

The study raises concerns about an age bias in medicine. "The medical community as a whole hasn't fully embraced this type of medical therapy for severe sepsis because of concerns about resource use and safety in older patients and questions about their subsequent quality of life," Ely said. "On one hand some older patients receive overly aggressive life support without benefit, but in the case of this new drug, physicians seem to practice ageism and don't use the available therapy to patients' full advantage.

"When patients are relatively healthy and active, we should take age out of the medical equation. Older patients need research specific to their outcomes and they need advocates," he said.

More than 2,000 people are diagnosed with severe sepsis every day, and this disease kills as many people as heart attacks -- 750 each day in the United States.. The problem continues to grow as the population ages. More than half of all ICU days are occupied by people 65 and older; the number of days per year spent in an ICU are seven-times greater for people over 75 than for those younger than 65.

The study builds on a previous study, the Protein C Worldwide Evaluation of Severe Sepsis (PROWESS), which ended in June 2000 when DAA (also known as activated protein C, or by its trade name Xigris) was approved by the Food and Drug Administration. In that study, 850 patients 65 years and older were randomized to receive placebo or DAA in a continuous intravenous drip for 96 hours to determine the drug's efficacy and safety when used to treat severe sepsis.

For the current study, Ely and colleagues followed a subset of 386 patients PROWESS, who were 75 years old and older at the time of drug administration, for an additional two years. Patients in that age group were eligible if they had a known or suspected site of infection, three or more signs of systemic inflammation and at least one sepsis-induced organ dysfunction.

One of the more common concerns among clinicians treating older patients is that DAA, an anti-inflammation, anti-thrombotic drug, is associated with a higher rate of bleeding (2.21 percent vs. 3.9 percent) as a side effect, Ely said. (DDA replaces a natural protein, "C", that is lost during sepsis, and thereby helps the body's ability to recover from the many abnormalities that occur during sepsis.) The study, however, showed that 65 patients could be treated with DAA before one serious bleeding event would occur, and that the rate of bleeding was similar among the young and old patients . Moreover, patients on DAA had "significant increases" in the number of days alive and off of the ventilator and out of the ICU and hospital. They had lower 28-day all-cause mortality (33.7 percent vs. 49.2 percent on placebo) and lower in-hospital mortality (36.9 percent vs. 52.5 percent on placebo), which translates into one life saved for every six to seven patients treated with DAA. The mortality benefit also remained significant even at two-year followup evaluation.

Ely writes in the study, "Although older ICU patients could potentially require more interventions and consume more health care resources, recent studies have shown that older patients actually receive less-aggressive care than do younger patients."

Age will continue to be a point of debate in the argument for health care rationing. But, Ely said, "we should strongly consider using drugs like DAA, when it's appropriate and safe, and when patients have an opportunity to have a high quality of life after fighting sepsis.

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