Corticosteroid Therapy of Septic Shock - Corticus

This study has been completed.
Sponsor:
Collaborators:
European Society of Intensive Care Medicine
International Sepsis Forum
The Gorham Foundation
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT00147004
First received: September 6, 2005
Last updated: April 23, 2008
Last verified: April 2008
  Purpose

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


Condition Intervention Phase
Shock, Septic
Drug: hydrocortisone sodium succinate
Drug: Placebo
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 500
Study Start Date: March 2002
Study Completion Date: November 2005
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Placebo
Drug: Placebo

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.

  Eligibility

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

Inclusion Criteria:

  1. Clinical evidence of infection within the previous 72 hours (may be present longer than 72 hours) (a, b, c, or d - only 1 required)

    1. Presence of polymorphonuclear cells in a normally sterile body fluid (excluding blood);
    2. Culture or Gram stain of blood, sputum, urine or normally sterile body fluid positive for a pathogenic micro-organism;
    3. 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);
    4. Other clinical evidence of infection - treated community acquired pneumonia, purpura fulminans, necrotising fascitis, etc.
  2. 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.

    1. Fever (temperature >38.3°C) or hypothermia (rectal temperature < 35.6°C);
    2. Tachycardia (heart rate of >90 beat/min);
    3. Tachypnea (respiratory rate > 20 breaths/min, PaC02<32 mmHg) or patient requires invasive mechanical ventilation;
    4. Alteration of the WBC count >12,000 cells/mm3, <4,000 cells/mm3 or >10% immature neutrophils (bands).
  3. Evidence of shock defined by (A + B- both required within the previous 72 hours (may NOT be present longer than 72 hours).

A. A systolic blood pressure < 90 mmHg or a decrease in SBP of more than 50 mmHg from baseline in previous hypertensive patients (for at least one hour) despite adequate fluid replacement OR need for vasopressors for at least one hour (infusion of dopamine ≥ 5 mcg/kg/min or any dose of adrenaline, noradrenaline, phenylephrine or vasopressin) to maintain a SBP ≥ 90 mmHg;

B. Hypoperfusion or organ dysfunction which is not the result of underlying diseases or drugs, but is attributable to sepsis, including one of the following:

  1. Sustained oliguria (urine output < 0.5 ml/kg/hr for a minimum of 1 hour)
  2. Metabolic acidosis [pH of < 7.3, or a base deficit of > or = 5.0 mmol/L, or an increased lactic acid concentration (> 2 mmol/L)].
  3. Arterial hypoxemia (Pa02/FI02<280 in the absence of pneumonia)(Pa02/FI02<200 in the presence of pneumonia).
  4. Thrombocytopenia - platelet count ≤ 100,000 cells/mm3.
  5. Acute altered mental status (Glasgow Coma Scale < 14 or acute change from baseline).

4. Informed Consent

5. Cortisol level at baseline and 60 minutes after 0.25 mg cosyntropin

Exclusion Criteria:

  1. Pregnancy
  2. Age less than 18.
  3. Underlying disease with a prognosis for survival of less than 3 months.
  4. Cardiopulmonary resuscitation within 72 hours before study.
  5. Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4 weeks before the study.
  6. 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.
  7. HIV positivity.
  8. Presence of an advanced directive to withhold or withdraw life sustaining treatment (i.e. DNR).
  9. Advanced cancer with a life expectancy less than 3 months.
  10. Acute myocardial infarction or pulmonary embolus.
  11. Another experimental drug study within the last 30 days.
  12. Moribund patients likely to die within 24 hours.
  13. Patients in the ICU for more than 2 months at the time of the start of septic shock.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00147004

  Show 57 Study Locations
Sponsors and Collaborators
Hadassah Medical Organization
European Society of Intensive Care Medicine
International Sepsis Forum
The Gorham Foundation
Investigators
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Charles Sprung, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT00147004     History of Changes
Other Study ID Numbers: QLK2-CT-2000-00589, EC- QLK2-CT-2000-00589
Study First Received: September 6, 2005
Last Updated: April 23, 2008
Health Authority: Austria: Federal Ministry for Health and Women
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Hadassah Medical Organization:
Septic shock
Steroids
Hydrocortisone
Mortality
Reversal of shock
Adrenal insufficiency

Additional relevant MeSH terms:
Shock
Shock, Septic
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on August 28, 2014