William L. Macias

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BACKGROUND In November 2001, the Food and Drug Administration (FDA) approved drotrecogin alfa (activated) (DrotAA) for adults who had severe sepsis and a high risk of death. The FDA required a study to evaluate the efficacy of DrotAA for adults who had severe sepsis and a low risk of death. METHODS We randomly assigned adult patients with severe sepsis(More)
BACKGROUND There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who(More)
OBJECTIVE To provide further evidence for the efficacy and safety of drotrecogin alfa (activated) treatment in severe sepsis. DESIGN Single-arm, open-label, trial of drotrecogin alfa (activated) treatment in severe sepsis patients. Enrollment began in March 2001 and day-28 follow-up completed in January 2003. SETTING ENHANCE took place in 25 countries(More)
BACKGROUND Both clopidogrel and prasugrel require biotransformation to active metabolites by cytochrome P450 (CYP) enzymes. Among persons treated with clopidogrel, carriers of reduced-function CYP2C19 alleles have significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse cardiovascular events. The effect of(More)
INTRODUCTION Drotrecogin alfa (activated; recombinant activated protein C) was shown to reduce 28-day all-cause mortality in patients with severe sepsis and to have an acceptable safety profile in 1690 patients studied in the F1K-MC-EVAD (PROWESS) trial. We analyzed all available data on the safety of treatment with drotrecogin alfa (activated) in 2786(More)
OBJECTIVE Early identification and treatment of severe sepsis can significantly reduce mortality rate. We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to standard care should be significantly related to 28-day survival. DESIGN Analysis of organ dysfunction data from two placebo-controlled severe sepsis(More)
OBJECTIVES We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. BACKGROUND Prasugrel is superior to clopidogrel in preventing ischemic(More)
Acute kidney injury (AKI) is common in critically ill patients with severe sepsis (SS), and the predictors of AKI in this population have not been well characterized. The study group was the placebo group of the Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) data set. PROWESS is a prospective, randomized,(More)
RATIONALE Patients with severe sepsis frequently receive prophylactic heparin during drotrecogin alfa (activated) (DrotAA) treatment due to risk of venous thromboembolic events (VTEs). Biological plausibility exists for heparin to reduce DrotAA efficacy and/or increase bleeding. OBJECTIVES Primary: demonstrate in adult patients with severe sepsis(More)
BACKGROUND Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a(More)