Activated Protein C and Corticosteroids for Human Septic Shock

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This study aims at comparing the efficacy and safety of recombinant human activated protein C to that of low dose of corticosteroids and at investigating the interaction between these drugs in the management of septic shock

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Versailles
• Collaborators: Assistance Publique - Hôpitaux de Paris; Ministry of Health, France
• Treatments: Cortisol succinate; Drotrecogin alfa activated; Fludrocortisone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Protein C

Criteria

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.