Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis

This chapter provides a summary of the landmark study known as the PROWESS Study. Does treatment with DAA reduce the rate of death from any cause among patients with severe sepsis? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The PROWESS trial demonstrated a mortality benefit for DAA among patients with severe sepsis. However, the subsequent ADDRESS, RESOLVE, and PROWESS-SHOCK trials did not demonstrate a benefit of the medication, thus calling the results of PROWESS into question.

Il trattamento di pazienti con sepsi grave mediante drotrecogin alfa: una valutazione economica con riferimento all’Italia

Sepsis can be defined as a spectrum of clinical conditions caused by the immune response of a host to infection or trauma and characterized by systemic inflammation and coagulation. Particularly in elderly, immunocompromised and critically ill patients, sepsis is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. In the US, sepsis is the leading cause of death in noncoronary ICU patients. Drotrecogin alfa, or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. Recently in a phase III trial (PROWESS), Drotrecogin alfa demonstrated significantly reduced mortality in severe sepsis patients at 28 days. In this trial important value factors for the assessment of costs and outcomes of severe sepsis were also considered. The purpose of the present study is to determine the economic burden of the treatment with Drotrecogin alfa, according to a cost-effectiveness analysis based on the data of the PROWESS trial. The study has been adapted to the italian health environment. As regards to the costs per surviving patient and costs per QALY (Quality Adjusted Life Year), the predicted cost-effectiveness ratio of drotrecogin alfa in severe sepsis patients is much lower than the standard values considered as acceptable in the international litterature.