Drotrecogin alfa activated: real-life use and outcomes for the UKReport as inadecuate

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Critical Care

, 12:R58

First Online: 22 April 2008Received: 13 August 2007Revised: 18 January 2008Accepted: 22 April 2008


IntroductionIn March 2001, the results of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis PROWESS study were published, which indicated a 6.1% absolute reduction in 28-day mortality. Drotrecogin alfa activated; DrotAA was subsequently approved for use in patients with severe sepsis.

MethodsIn December 2002, critical care units in England, Wales and Northern Ireland were invited to participate in an audit of DrotAA. Data for each infusion of DrotAA were linked to case mix and outcome data from a national audit. Use of DrotAA was described and a nonrandomized comparison of effectiveness was conducted.

Results1,292 infusions of DrotAA were recorded in 112 units; 61% commenced during the first 24 hours in the unit. The majority 77% of patients had three or more organs failing; lung 42% and abdomen 40% were the most common primary sites of infection. Crude hospital mortality was high 45%; at 28 days, only 18% had left acute hospital and 19% were still in the unit. For 30%, the full 96-hour infusion was not completed; 24% of infusions were interrupted; 8.1% experienced one or more serious adverse events, of which 77% were serious bleeding events. Of eight relative risks estimated from individually-matched 0.75 to 0.85 and propensity-matched 0.82 to 0.90 controls, seven were consistent with the results of PROWESS. Restricting the analysis to patients receiving DrotAA during the first 24 hours resulted in larger treatment effects relative risks 0.62 to 0.81. For all matches, similar patterns were seen across subgroups. No effect of DrotAA was seen for two organs failing or lower severity scores, compared with a significant mortality reduction for three or more organs failing or higher severity scores.

ConclusionUse of DrotAA was approximately one in 16 for admissions meeting the definition for severe sepsis and with two or more organs failing. Patients receiving DrotAA were younger and more severely ill but were less likely to have serious conditions in their past medical history. Nonrandomized estimates for the effectiveness of DrotAA were consistent with the findings of PROWESS. DrotAA appeared not to be effective in patients with less severe disease.

AbbreviationsCMPCase Mix Programme

DrotAAdrotrecogin alfa activated

ENHANCEExtended Evaluation of Recombinant Activated Protein C

FDAFood and Drug Administration

ICNARCIntensive Care National Audit and Research Centre

PROWESSRecombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis.

Electronic supplementary materialThe online version of this article doi:10.1186-cc6879 contains supplementary material, which is available to authorized users.

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Author: Kathryn M Rowan - Catherine A Welch - Emma North - David A Harrison

Source: https://link.springer.com/

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