Septic Shock Data Show Why Drug Pulled (CME/CE)
The compound, a recombinant version of human activated protein C, was initially approved in 2011 after a major trial showed a survival benefit.
But subsequent studies failed to deliver similar results, and a new trial – dubbed PROWESS-SHOCK -- was ordered to test the hypothesis that the compound would reduce mortality compared with placebo in patients with septic shock.
That study, Thompson and colleagues reported, included data on 1,697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors.
They were randomly assigned to get drotrecogin alfa or placebo for 96 hours, and the primary outcome of the study was death from any cause after 28 days.
But, they found, at 28 days: 223 of 846 patients in the active treatment group and 202 of 834 in the placebo group had died – 26.4% versus 24.2%.
At 90 days, the pattern was similar -- 34.1% in the active arm and 32.7% in the placebo arm (RR 1.04), which again was not significant.
Among patients with severe protein C deficiency at baseline, 28.7% in the drotrecogin alfa group were dead after 28 days, compared with 30.8% in the placebo group.
"The fact that we found no benefit in any of the prespecified subgroups should reassure clinicians" who no longer have access to the drug, Thompson and colleagues concluded.
The study also "should end any further pursuit of a niche for (drotrecogin alfa) in the treatment of sepsis," argued Richard Wenzel, MD, and Michael Edmond, MD, both of Virginia Commonwealth University in Richmond, Va.
In an editorial accompanying the journal publication, they said the findings are a "setback" but should prompt renewed efforts to find effective treatments for sepsis.
An important weakness of the study, they argued, was that it did not achieve its planned statistical power of 80% because it was based on a sample size that was too small.