Drotrecogin alfa (Xigris®) for severe sepsis

Findings by SBU Alert

Version: 1

Technology and target group

Sepsis is a life-threatening condition characterized by a systemic inflammatory response to infection. The condition is classified as severe sepsis if at least one vital organ system ceases to function. Septic shock is diagnosed when low arterial blood pressure that does not resolve with adequate fluid resuscitation occurs. Mortality is approximately 20 percent in cases of severe sepsis and 45 percent in cases of septic shock. Drotrecogin alfa (Xigris®) is a new drug approved August 2002 in Sweden as an adjunct to standard treatment of severe sepsis in adults. The estimated size of the target group is below 500 patients per year.

Patient benefits and risks

One randomized, placebo-controlled, double-blind, multicenter trial that compared drotrecogin alfa (Xigris®) to placebo was identified. The trial included 1 690 patients from 11 countries. Mortality at 28 days after the start of treatment was 30.8 percent in the placebo group and 24.7 percent in the treatment group, ie, an absolute risk reduction of 6.1 percentage units. The benefit was shown only for the most severely ill patients according to a severity of disease classification system (APACHE II). This suggests that 1 death per 16 treated patients could be avoided (NNT=16). The risk for severe hemorrhage in conjunction with treatment was 1.5 percent.

Economic aspects

The drug cost of drotrecogin alfa (Xigris®) is 85 000 Swedish kronor (SEK) per patient. Two studies have estimated cost effectiveness. Both of these studies have estimated the cost per life-year gained to be approximately 260 000 SEK and the cost per quality-adjusted life-year (QALY) to be approximately 400 000 SEK. If the calculation is based only on data for the most severely ill patients, the cost per life-year gained is estimated to be approximately 160 000 SEK and the cost per quality-adjusted life-year approximately 240 000 SEK.

Scientific evidence

Currently there is moderate* scientific evidence that show positive effects of drotrecogin alfa on survival in patients with severe sepsis. There is moderate* scientific evidence of its cost effectiveness. Results from long-term followup on the risks and benefits of treatment have yet to be published. Therefore, it is essential to systematically monitor clinical experiences at the national level.

*This assessment by SBU Alert uses a 4-point scale to grade the quality and evidence of the scientific documentation. The grades indicate: (1) good, (2) moderate, (3) poor, or (4) no scientific evidence on the subject.

This summary is based on a report prepared at SBU in collaboration with Sten Walther, MD, Örebro University Hospital and Thomas Nolin, MD, Centralsjukhuset, Kristianstad. It has been reviewed by Bengt Ljungberg, MD, Medical Products Agency.

The complete report is available only in Swedish.

SBU Alert is a service provided by SBU in collaboration with the Medical Products Agency, the National Board of Health and Welfare, and the Federation of Swedish County Councils.

References

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13. Anti-Infective Advisory Committee. Drotrecogin alfa (activated) [recombinant human activated protein C (rhAPC)] XigrisT. U.S. Food and Drug Administration. 2001. FDA briefing document.
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