Unblinding plan of PROWESS-SHOCK trial
Ospedale S. Giovanni Battista-Molinette, Università di Torino, Torino, Italy, .Intensive Care Medicine (Impact Factor: 7.21). 06/2011; 37(8):1384-5. DOI: 10.1007/s00134-011-2272-7
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ABSTRACT: Septic shock causing or complicating critical surgical illness results in high mortality. Drotrecogin alfa (activated), known also as recombinant human activated protein C (rhAPC) has become controversial as therapy, owing to persisting questions of efficacy and safety. We hypothesized rhAPC to be effective therapy for critically ill surgical patients with septic shock. Open-label therapy with rhAPC (by predefined criteria) of 108 critically ill surgical patients. Treated patients were matched individually in prospect for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE)-II and -III scores, site of infection, and organism (0-2 points each, maximum 12 points) with 108 patients from our 15,000-patient surgical intensive care unit database who did not receive rhAPC. No match was accepted if <6 points. Multiple organ dysfunction (MOD) scores and data regarding cortisol concentrations, bleeding complications, and transfusion requirements were collected. The primary endpoint was 28-day mortality, with mortality for hospitalization and resolution of organ dysfunction as secondary endpoints. Statistical analyses included ANOVA, c statistic, binary logistic regression, and Kaplan-Meier time-to-event and Cox proportional hazards analyses; α=0.05. The mean match score was 9.2±0.1 points (range, 6-12 points). Patients were well matched by all criteria, including baseline MOD score (9.5±0.7 vs. 9.8±0.3 points, p=0.66). Mean age was 68.1±1.1 years (p=0.49), Mean APACHE-III score was 99.6±1.5 points (p=0.87). Mean time to rhAPC administration was 25±3 h. Survival at 28 days after rhAPC was 71.3% vs. 49.1% (p=0.001); hospital survival was 57.4% vs. 40.7% (p=0.02). By logistic regression, rhAPC therapy resulted in improved 28-day survival (OR 2.57, 95% CI 1.46-4.52, p=0.001) (model χ2 11.244, p=0.001); and hospital survival (OR 1.96, 95% CI 1.14-3.36, p=0.015) (model χ2 6.03, p=0.014). The MOD score decreased significantly (p=0.012) during rhAPC therapy. Therapy with rhAPC appeared to improve survival in surgical ICU patients with life-threatening infection characterized by septic shock and organ dysfunction.Surgical Infections 12/2011; 12(6):443-9. DOI:10.1089/sur.2011.133 · 1.45 Impact Factor
Article: The Last Xigris (R) SurvivorSurgical Infections 12/2011; 12(6):423-5. DOI:10.1089/sur.2011.9909 · 1.45 Impact Factor
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ABSTRACT: Sepsis (a generalized blood stream infection) is common in neonates. Severe sepsis carries a high mortality and morbidity even with current critical care management. Activated Protein C (APC) is a protein formed within the human body to prevent formation of blood clots and helps in breaking down clots. Recombinant human APC (rhAPC) is a synthesized version of APC using recombinant technology. It has been shown to reduce mortality in severe sepsis in adults. The review authors investigated whether treatment of severe sepsis in newborn infants with rhAPC will help to reduce mortality and severe morbidity. The review authors found no controlled studies in this age group. On October 25, 2011 rhAPC (Xigris®) was withdrawn from the market by Eli Lilly due to side effect in adults. RhAPC should no longer be used in any age category and the product should be returned to the distributor.Cochrane database of systematic reviews (Online) 04/2012; 4(4):CD005385. DOI:10.1002/14651858.CD005385.pub3 · 6.03 Impact Factor
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