Activated Protein C and Corticosteroids for Human Septic Shock

Inclusion Criteria: * hospitalized in intensive care unit for less than 7 days * septic shock for less than 24 hours * at least one proven site of infection * at least 2 organ dysfunction as defined by a SOFA score =or\> to 3 for at least 6 consecutive hours * need for vasopressor (dopamine =or\>15µg/kg/min or epinephrine/norepinephrine at =or\>0,25 µg/kg/min for at least 6 consecutive hours, to maintain systolic arterial pressure at 90 mmHg or more OR mean arterial pressure at 6( mmHg or more * informed consent Exclusion Criteria: * pregnancy or breath feeding * decision not to resuscitate * underlying disease with an estimated life expectancy of less than 1 month * formal indication for corticosteroids * recent surgery (ie within the past 72 hours) or a surgery at high risk of bleeding * gastro-intestinal bleeding within the past 6 weeks * chronic liver disease (Child C) * recent trauma (ie within the past 72 hours) * intracranial process * history of stroke, CNS bleeding or traumatic brain injury within the past 3 months * platelet counts of less than 30000 per cubic millimeter * formal indication for curative anticoagulant; prophylactic use of heparin is allowed * any condition of high risk of bleeding as per patient's primary physicians * hypersensitivity of activated drotrecogin alpha or any other component of the drug * no affiliation to a social security Amendments to eligibility criteria were: On 27/03/2008: Changes in following exclusion criteria : * "surgical procedure in the past 7 days" was changed for "surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h". * "chronic liver disease" was clarified as "chronic liver disease with Child score C". * "severe thrombopenia" was clarified "as severe thrombopenia (\<30,000/mm3, before transfusion). On 25/08/2009: The exclusion criteria: surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h" was changed for "surgical procedure within 12 hours, or any surgery associated with high risk of bleeding On 11/06/2010: the inclusion criteria: admitted to the ICU for \< 7 days was removed; and a new exclusion criteria was added: "patients who had a previous episode of sepsis during the same hospital stay On 18/04/2012: following the withdrawal of DAA from the market: the following exclusion criteria (only related to DAA) were removed : 1. any surgery in the past 12 hours, or any surgery associated with high risk of bleeding; 2. chronic liver disease with a Child score C; 3. recent trauma; 4. any intracranial mass, or stroke or head injury in the past 3 months; 5. severe thrombocytopenia (\< 30.000 /mm3, before platelet transfusion); 6. formal indication for anticoagulation, or any other condition associated with increased risk of bleeding, as appreciated by the patient's physician.