Activated Protein C and Corticosteroids for Human Septic Shock - Full Text View

Sponsor:	University of Versailles
Collaborators:	Assistance Publique - Hôpitaux de Paris Ministry of Health, France
Information provided by:	University of Versailles
ClinicalTrials.gov Identifier:	NCT00625209

Purpose

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

Condition	Intervention	Phase
Septic Shock	Drug: 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	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study
Official Title:	Phase III of Recombinant Human Activated Protein C and Low Dose of Hydrocortisone and Fludrocortisone in Adult Septic Shock

Resource links provided by NLM:

Drug Information available for: Hydrocortisone acetate Hydrocortisone Protein C Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Drotrecogin alfa Hydrocortisone 21-sodium succinate Fludrocortisone Hydrocortisone cypionate Fludrocortisone 21-acetate Cortisol succinate Cortisol 21-phosphate

U.S. FDA Resources

Further study details as provided by University of Versailles:

Primary Outcome Measures:

90-day mortality [ Time Frame: 90 day ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

mortality at 28 day [ Time Frame: 28-day ] [ Designated as safety issue: Yes ]
mortality at hospital discharge [ Time Frame: hospital discharge ] [ Designated as safety issue: Yes ]
mortality at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
decision to withhold or withdraw active treatments [ Time Frame: up to 90 days ] [ Designated as safety issue: No ]
Time to wean vasopressor therapy [ Time Frame: up to 90 days ] [ Designated as safety issue: No ]
time to achieve an SOFA score of less than 6 [ Time Frame: up to 90 days ] [ Designated as safety issue: No ]
Length of intensive care unit and hospital stay [ Time Frame: up to hospital discharge ] [ Designated as safety issue: Yes ]
acquisition of new infection [ Time Frame: up to 180 days ] [ Designated as safety issue: Yes ]
bleeding events [ Time Frame: up to 90 days ] [ Designated as safety issue: Yes ]
neurological sequels at intensive care unit discharge and at 90 and 180 days [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1280
Study Start Date:	March 2008
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator placebo of hydrocortisone, placebo of fludrocortisone and placebo of activated protein C	Drug: placebos placebo of hydrocortisone as an iv bolus every 6 hours for seven days plus placebo of fludrocortisone given through the nasogastric tube once a day for seven days plus placebo of activated protein C given as a continuous infusion for 96 hours
2: Active Comparator Hydrocortisone plus fludrocortisone and a placebo of activated protein C	Drug: hydrocortisone and fludrocortisone and placebo hydrocortisone will be given as 50mg iv bolus every 6 hours for seven days and a tablet of 50µg of fludrocortisone will be given once a day via the nasogastric tube for seven days and a placebo of activated protein C will be given as a continuous infusion for 96 hours
3: Active Comparator placebo of hydrocortisone, placebo of fludrocortisone and activated protein C	Drug: recombinant human activated protein C and placebos activated protein C will be given as a continuous infusion at a dose of 24 µg/kg/h four 96 hours and hydrocortisone placebo as an iv bolus every 6 hours and fludrocortisone placebo once a day through the gastric tube will be given for seven days
4: Active Comparator hydrocortisone plus fludrocortisone plus activated protein C	Drug: recombinant human activated protein C and hydrocortisone and fludrocortisone 96 hours continuous infusion of 24µg/kg/h of activated protein C plus seven day treatment with 50mg iv bolus of hydrocortisone every 6 hours and 50µg of fludrocortisone via the nasogastric tube once a day

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625209

Contacts

Contact: Djillali Annane, MD	33147107786	djillali.annane@rpc.aphp.fr
Contact: Christian Brun Buisson, MD	33149812386	christian.brun-buisson@hmn.aphp.fr

Locations

France
Raymond Poincaré Hospital	Recruiting
Garches, France, 92380
Contact: Djillali Annane, MD
Principal Investigator: Djillali Annane
Henri Mondor Hospital	Recruiting
Créteil, France, 94
Contact: Christian Brun Buisson
Principal Investigator: Christian Brun Buisson
Pitié Salpêtrière Hospital	Recruiting
Paris, France, 75
Contact: Jean Chastre
Principal Investigator: Jean Chastre
Saint Josef Hospital	Recruiting
Paris, France, 75
Contact: Benoit Misset
Principal Investigator: Benoit Misset

Sponsors and Collaborators

University of Versailles

Assistance Publique - Hôpitaux de Paris

Ministry of Health, France

Investigators

Principal Investigator:	Benoit Misset, MD	St. Joseph Hospital
Principal Investigator:	Claude Martin, MD	Assistance Publique Hopitaux de Marseille, hôpital Nord
Principal Investigator:	Alain Cariou, MD	Assistance Publique Hôpitaux de Paris, Hôpital Cochin
Principal Investigator:	Jean Carlet, MD	St. Joseph Hospital
Principal Investigator:	Christian Brun Buisson, MD	Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor
Principal Investigator:	Djillali Annane, MD	Assistance Publique Hôpitaux de Paris, Hôpital Raymond Poincaré

More Information

No publications provided

Responsible Party:	Assistance Publique Hôpitaux de Paris ( Djillali Annane )
Study ID Numbers:	P070128
Study First Received:	February 19, 2008
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00625209 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by University of Versailles:

septic shock
coagulation
immunomodulation
survival

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Systemic Inflammatory Response Syndrome
Anti-Infective Agents
Drotrecogin alfa activated
Anticoagulants
Hydrocortisone
Molecular Mechanisms of Pharmacological Action
Cortisol succinate
Hematologic Agents
Fibrinolytic Agents
Cardiovascular Agents
Infection

Pharmacologic Actions
Inflammation
Fibrin Modulating Agents
Sepsis
Pathologic Processes
Shock
Protein C
Therapeutic Uses
Shock, Septic
Fludrocortisone
Hydrocortisone acetate

ClinicalTrials.gov processed this record on February 08, 2010