Ask the Experts - Use of Protein C in Sepsis
Is protein C in use in the United States for sepsis, and what are the indications?

Aziz ur Rahman, MBBS

Activated Protein C (APC) is now under expedited review by the Food and Drug Administration (FDA) in the United States. Their review is based on preclinical data, and primarily on The Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study recently published in TheNew England Journal of Medicine (NEJM). Bernard and colleagues found that treatment with APC reduced absolute mortality by 6% and relative risk of death by 19%. This effect appeared consistent in all groups studied.

A more recently published article in NEJM confirmed the mechanism of action of APC in patients with meningococcal sepsis. In this subsequent study, Faust and coworkers found that activation of native protein C was impaired in this patient population.

The indications for the administration of APC will likely initially be based on the inclusion criteria of the PROWESS study, which included patients with sepsis syndrome and single organ dysfunction; however, the majority of patients had at least 2 organ system dysfunctions, with respiratory failure the most common.

The FDA is expected to complete its review of APC in September or October 2001.