Corticosteroid Therapy of Septic Shock - Corticus (Corticus)
Drug: hydrocortisone sodium succinate
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Corticosteroid Therapy of Septic Shock - Corticus. A Multi-National, Prospective, Double-Blind, Randomized, Placebo-Controlled Study|
- 28 day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- 28 day all cause mortality in the total group. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- 28 day all cause mortality in responders. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- One year mortality in nonresponders, total and responders. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- ICU and hospital mortality. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- Organ system failure reversal, especially shock. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- Duration of ICU and total hospitalisation. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2002|
|Study Completion Date:||November 2005|
|Primary Completion Date:||November 2005 (Final data collection date for primary outcome measure)|
hydrocortisone sodium succinate
Drug: hydrocortisone sodium succinate
50 mg intravenous bolus every six hours for 5 days, then tapered to 50 mg intravenously every 12 hours for days 6-8, 50 mg every 24 hours for days 9-11 and then stopped
Placebo Comparator: 2
The use of steroids in septic shock remains controversial. The purpose of this study is to determine whether hydrocortisone decreases 28-day mortality in patients with septic shock. The primary end point will be 28-day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH). Secondary endpoints will be 28 day all cause mortality in the total group and in responders, ICU and hospital mortality, one year mortality, organ system failure reversal especially shock, and duration of ICU and total hospitalisation.
In a double-blinded fashion (randomized on a 1:1 basis), patients receive 50 mg intravenously every 6 hours for 5 days. After 5 days, treatment will be tapered with 50 mg given intravenously every 12 hours for days 6-8, then 50 mg every 24 hours for days 9-11, and then stopped.
All concomitant treatments, including antibiotics, fluids, vasopressors and ancillary therapies will be given at the discretion of the primary care physician. Evidence-based guidelines for the management of severe sepsis and septic shock by the International Sepsis Forum (Intensive Care Med 2001;27:S124-S134) are encouraged to be followed.
All serious adverse events (SAE) which occur between days 0 and 28, which are unexpected and/or considered possibly or probably related to the study medication, must be documented and reported within 24 hours to the Safety and Efficacy Monitoring Committee. Non-serious adverse events will be listed on the case report form if they are unexpected and believed to be related to the study drug during days 0 to 14.
Specific adverse events which will be monitored closely because of their relationship to corticosteroids and shock are:
- Use of corticosteroids, i.e. gastrointestinal bleeding and superinfection; hyperglycemia, hypernatremia, muscular weakness, etc.
- Shock and use of vasopressors, i.e. stroke, acute myocardial infarction and peripheral ischemia.
In addition, substudies will include harmonization of cortisol by comparing cortisol levels measured in local laboratories and a central laboratory, immune and neuro-endocrine interactions, neuromuscular weakness and cytokines.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00147004
Show 57 Study Locations
|Study Chair:||Charles L Sprung, MD||Hadasah Medical Organization|
|Study Director:||Djillali Annane, MD||Hopital Raymond Poincare|
|Study Director:||Josef Briegel, MD||Ludwig-Maximilian-Universitaet Muenchen|
|Study Director:||Didier Keh, MD||Charite Campus Virchow-Klinikum|
|Study Director:||Rui Moreno, MD||Hospital de St. António dos Capuchos|
|Study Director:||Didier Pittet, MD||University Hospital, Geneva|
|Study Director:||Mervyn Singer, MD||University College, London|