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Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock (COIITSS)

This study has been completed.
Sponsor:
Collaborator:
Assistance Publique - Hôpitaux de Paris
Information provided by:
University of Versailles
ClinicalTrials.gov Identifier:
NCT00320099
First received: April 27, 2006
Last updated: April 5, 2010
Last verified: April 2010

April 27, 2006
April 5, 2010
January 2006
January 2009   (final data collection date for primary outcome measure)
In-hospital mortality [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
In-hospital mortality
Complete list of historical versions of study NCT00320099 on ClinicalTrials.gov Archive Site
  • Secondary outcomes : [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
  • 90-day and 180-day mortality. [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
  • Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation) [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
  • Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8 [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
  • Hospital length of stay. [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
  • Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
  • Muscle weakness at discharge from intensive care unit, 90-day and 180-day [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
  • Post traumatic stress disorders [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
  • Secondary outcomes :
  • 90-day and 180-day mortality.
  • Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation)
  • Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8
  • Hospital length of stay.
  • Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion
  • Muscle weakness at discharge from intensive care unit, 90-day and 180-day
  • Post traumatic stress disorders
Not Provided
Not Provided
 
Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock
Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock

This study will compare, in adults with septic shock, the safety and efficacy of a combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids. In addition, this study will compare the efficacy and safety of hydrocortisone alone versus hydrocortisone plus fludrocortisone

Objectives:

Comparison, in patients with septic shock, of efficacy and safety of the combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids; and of efficacy and safety of hydrocortisone alone versus hydrocortisone plus fludrocortisone Methods

Study design :

This is a multicenter, prospective, randomised trial on parallel groups

Study treatments :

Experimental arm A:

A1=50 mg iv every 6 hours of hydrocortisone (hemisuccinate), 50µg through the nasogastric tube of 9 alpha fludrocortisone, for 7 days AND strict control of blood glucose levels with a target of 4,4 to 6 mmol/L using continuous iv infusion of insulin up to intensive care unit discharge.

A2=50 mg iv every 6 hours of hydrocortisone (hemisuccinate) for 7 days AND strict control of blood glucose levels with a target of 4,4 to 6 mmol/L using continuous iv infusion of insulin up to intensive care unit discharge.

Control arm B:

B1:50 mg iv every 6 hours of hydrocortisone (hemisuccinate), 50µg through the nasogastric tube of 9 alpha fludrocortisone, for 7 days.

B2:50 mg iv every 6 hours of hydrocortisone (hemisuccinate)for 7 days. Study Primary outcome : In-hospital mortality

Sample size calculation :

The expected in-hospital mortality rate in the control group is 50%. To detect an absolute reduction in in-hospital mortality rate of 12.5 %, that is 37.5% in the experimental arm versus 50% in the control arm, and considering risk alpha of 0,05 and a risk beta of 0,20, 254 patients per treatment arms are needed, for a total of 508 patients.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Septic Shock
  • Drug: recombinant human insulin
    intensive insulin therapy as a continuous infusion to maintain blood glucose levels between 4 and 6 mmol/l
  • Drug: hydrocortisone
    50 mg as iv bolus every 6 hours for 7 days
  • Drug: fludrocortisone
    50 µg once a day via a nasogastric tube for seven days
  • Drug: Hydrocortisone
    hydrocortisone 50mg q6 for 7 days
  • Active Comparator: 1
    Hydrocortisone and convention glycemic control
    Interventions:
    • Drug: hydrocortisone
    • Drug: Hydrocortisone
  • Experimental: 2
    Hydrocortisone and fludrocortisone and conventional glucose control
    Interventions:
    • Drug: hydrocortisone
    • Drug: fludrocortisone
  • Experimental: 3
    Hydrocortisone and intensive insulin therapy
    Interventions:
    • Drug: recombinant human insulin
    • Drug: hydrocortisone
  • Experimental: 4
    hydrocortisone, fludrocortisone and intensive insulin therapy
    Interventions:
    • Drug: recombinant human insulin
    • Drug: hydrocortisone
    • Drug: fludrocortisone
COIITSS Study Investigators, Annane D, Cariou A, Maxime V, Azoulay E, D'honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santré C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec'h C, Mayaux J, Lejeune J, Chevret S. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):341-8. doi: 10.1001/jama.2010.2. Erratum in: JAMA. 2010 May 5;303(17):1698.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
508
February 2009
January 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

Patients admitted in intensive care units for septic shock and meeting all following criteria

  • Proven infection
  • Need for vasopressor to maintain systemic arterial tension above 90 mmHg
  • Multiple organ dysfunction as defined by a SOFA score ³ 8.
  • Need for treatment with moderate dose of corticosteroids

Exclusion Criteria:

One of the following :

  • Pregnancy
  • Less than 18 years old
  • Moribund (i.e. expected to die on day of intensive care unit admission)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00320099
AOM04100, P040421
Yes
Djillali Annane, AP-HP - University of Versailles SQY
University of Versailles
Assistance Publique - Hôpitaux de Paris
Study Chair: Djillali annane, MD, PhD Assistance Publique Hôpitaux de Paris - University of Versailles
University of Versailles
April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP