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Recombinant Human Activated Protein C for Adults with Septic Shock: a Randomized Controlled Trial.
Am J Respir Crit Care Med. 2013 Mar 22;
Authors: Annane D, Timsit JF, Megarbane B, Martin C, Misset B, Mourvillier B, Siami S, Chagnon JL, Constantin JM, Petitpas F, Souweine B, Amathieu R, Forceville X, Charpentier C, Tesniere A, Chastre J, Bohe J, Colin G, Cariou A, Renault A, Brun-Buisson C, Eric B, for The APROCCHSS Trial Investigators
Abstract
BACKGROUND: A decade after drotrecogin alfa activated (DAA) was released on the market worldwide, its benefit-to-risk ratio remains a matter of debate. OBJECTIVE: The current investigator-led trial was designed to evaluate the efficacy and safety of DAA, in combination with low-dose steroids, in adults with persistent septic shock. METHODS: This was a multicenter (24 intensive care units), placebo-controlled, double-blind, 2x2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were randomly assigned to DAA alone (24 microgram per kilogram per hour for 96 hours), hydrocortisone and fludrocortisone alone, their respective combinations or their respective placebos. Primary outcome was mortality rate at day-90. MEASUREMENTS AND RESULTS: On October 25 2011, the trial was suspended following the withdrawal from the market of DAA. The Scientific Committee decided to continue the trial according to a two-parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension. At the time trial was suspended, 411 patients had been recruited, 208 had received DAA and 203 had received its placebo. There was no significant interaction between DAA and low-dose steroids (P=0.47). At day-90, there were 99/208 (47.6%) deaths in patients with DAA and 94/203 (46.3%) deaths in patients with its placebo (P=0.79). There was no evidence for a difference between DAA and its placebo for any secondary outcomes or serious adverse events. CONCLUSION: In adults with established and severe septic shock, DAA showed no evidence of benefit or harm. Clinical trial registration information available at www.clinicaltrials.gov, i.d. NCT00625209.
PMID: 23525934 [PubMed - as supplied by publisher]