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Activated Protein C and Corticosteroids for Human Septic Shock

Information source: University of Versailles
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Septic Shock

Intervention: placebos (Drug); hydrocortisone and fludrocortisone and placebo (Drug); recombinant human activated protein C and placebos (Drug); recombinant human activated protein C and hydrocortisone and fludrocortisone (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: University of Versailles

Official(s) and/or principal investigator(s):
Benoit Misset, MD, Principal Investigator, Affiliation: St. Joseph Hospital Health Center
Claude Martin, MD, Principal Investigator, Affiliation: Assistance Publique Hopitaux de Marseille, hôpital Nord
Alain Cariou, MD, Principal Investigator, Affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Cochin
Jean Carlet, MD, Principal Investigator, Affiliation: St. Joseph Hospital Health Center
Christian Brun Buisson, MD, Principal Investigator, Affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor
Djillali Annane, MD, Principal Investigator, Affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Raymond Poincaré


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

Clinical Details

Official title: Phase III of Recombinant Human Activated Protein C and Low Dose of Hydrocortisone and Fludrocortisone in Adult Septic Shock

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 90-day mortality

Secondary outcome:

mortality at 28 day

mortality at hospital discharge

mortality at 6 months

decision to withhold or withdraw active treatments

Time to wean vasopressor therapy

time to achieve an SOFA score of less than 6

Length of intensive care unit and hospital stay

acquisition of new infection

bleeding events

neurological sequels at intensive care unit discharge and at 90 and 180 days

Detailed description: Septic shock still places a burden in the healthcare system round around the world. In the early 20ties, clinical trials suggested potential benefits from activated protein C in severe sepsis and of corticosteroids when given to adults with refractory shock. More recent studies suggested that patients with moderate sepsis or septic shock may not benefit from either activated protein C or corticosteroids. Therefore, current international guidelines suggest that physicians may consider using these drugs in the more severe cases of sepsis. The main risk associated with the use of activated protein C is bleeding and the main risk associated with the use of steroids is superinfection. It is paramount that a new adequately powered trial explores the benefit/risk ratio of these two drugs and of their combination in a population of adult patients with septic shock. After the withdrawal of Xigris in October 2011, the study was suspended and restarted in June 2012 to investigate the benefit to risk ratio of corticosteroids.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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

Locations and Contacts

Henri Mondor Hospital, Créteil 94, France

Raymond Poincaré Hospital, Garches 92380, France

Pitié Salpêtrière Hospital, Paris 75, France

Saint Josef Hospital, Paris 75, France

Additional Information

Starting date: March 2008
Last updated: August 2, 2015

Page last updated: August 23, 2015

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