Corticosteroid Therapy of Septic Shock - Corticus. A Multi-National, Prospective, Double-Blind, Randomized, Placebo-Controlled Study

Hadassah Medical Organization57 sites in 9 countries500 target enrollmentMarch 2002

ConditionsShock, Septic

Interventionshydrocortisone sodium succinate Placebo

Drugshydrocortisone sodium succinate Placebo

Overview

Phase: Phase 3
Intervention: hydrocortisone sodium succinate
Conditions: Shock, Septic
Sponsor: Hadassah Medical Organization
Enrollment: 500
Locations: 57
Primary Endpoint: 28 day mortality in all the non-responders to ACTH (< or = 9 mcg/dl or 250 nmol/L post ACTH)
Status: Completed
Last Updated: 18 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of the study is to determine whether steroids decrease 28-day mortality in patients with septic shock.

Detailed Description

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: 1. Use of corticosteroids, i.e. gastrointestinal bleeding and superinfection; hyperglycemia, hypernatremia, muscular weakness, etc. 2. 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.

Registry

clinicaltrials.gov

Start Date

March 2002

End Date

November 2005

Last Updated

18 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hadassah Medical Organization

Eligibility Criteria

Inclusion Criteria

•Clinical evidence of infection within the previous 72 hours (may be present longer than 72 hours) (a, b, c, or d - only 1 required)
•Presence of polymorphonuclear cells in a normally sterile body fluid (excluding blood);
•Culture or Gram stain of blood, sputum, urine or normally sterile body fluid positive for a pathogenic micro-organism;
•Focus of infection identified by visual inspection (e.g. ruptured bowel with the presence of free air or bowel contents in the abdomen found at the time of surgery, wound with purulent drainage);
•Other clinical evidence of infection - treated community acquired pneumonia, purpura fulminans, necrotising fascitis, etc.
•Evidence of a systemic response to infection as defined by the presence of two or more of the following signs within the previous 24 hours. These signs may be present longer than 72 hours.
•Fever (temperature \>38.3°C) or hypothermia (rectal temperature \< 35.6°C);
•Tachycardia (heart rate of \>90 beat/min);
•Tachypnea (respiratory rate \> 20 breaths/min, PaC02\<32 mmHg) or patient requires invasive mechanical ventilation;
•Alteration of the WBC count \>12,000 cells/mm3, \<4,000 cells/mm3 or \>10% immature neutrophils (bands).

Exclusion Criteria

•Age less than
•Underlying disease with a prognosis for survival of less than 3 months.
•Cardiopulmonary resuscitation within 72 hours before study.
•Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4 weeks before the study.
•Administration of chronic corticosteroids in the last 6 months or acute steroid therapy (any dose) within 4 weeks (including inhaled steroids). Topical steroids are not exclusions.
•HIV positivity.
•Presence of an advanced directive to withhold or withdraw life sustaining treatment (i.e. DNR).
•Advanced cancer with a life expectancy less than 3 months.
•Acute myocardial infarction or pulmonary embolus.
•Another experimental drug study within the last 30 days.