Decreasing mortality withdrotrecogin alfa in high riskseptic patientsA meta-analysis ofrandomized trials in adultpatients with multiple organfailure and mortality

ABSTRACT

Objective. Sepsis is a complex inflammatory disease, rising in response to infection. Drotrecogin alfa, approved in 2001 forsevere sepsis, has been withdrawn from the market. The aim of this study was to assess if drotrecogin alfa-activated canreduce mortality in the more severe septic patients.Methods. We searched PubMed, Embase, Scopus, BioMedCentral, and in Clinicaltrials. gov databases to identify everyrandomized study performed on drotrecogin alfa-activated in any clinical setting in humans, without restrictions on dose ortime of administration. Our primary end-point was mortality rate in high risk patients. Secondary endpoints were mortality inall patients, in patients with an Acute Physiology and Chronic Health Evaluation (APACHE) 2 score ≥ 25 and in those withan APACHE 2 score ≤25.Results. Five trials were identified and included in the analysis. They randomized 3196 patients to drotrecogin alfa and 3111to the control group. Drotrecogin alfa was associated with a reduction in mortality (99/263 [37.6%] vs 115/244 [47.1%], riskratios (RR) = 0.80[0.65; 0.98], p = 0.03) in patients with multiple organ failure and a mortality risk in the control group of>40%, but not in the overall population or in lower risk populations.Conclusions. In high risk populations of patients with multiple organ failure and a mortality of >40% in the control group,Drotrecogin alfa may still have a role as a lifesaving treatment. No beneficial effect in low risk patients was found. An individualpatient meta-analysis including all randomized controlled trial on sepsis is warranted, along with new studies on similardrugs such as protein C zymogen.