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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00320099
Recruitment Status : Completed
First Posted : May 3, 2006
Last Update Posted : April 6, 2010
Sponsor:
Collaborator:
Assistance Publique - Hôpitaux de Paris
Information provided by:
University of Versailles

Tracking Information
First Submitted Date  ICMJE April 27, 2006
First Posted Date  ICMJE May 3, 2006
Last Update Posted Date April 6, 2010
Study Start Date  ICMJE January 2006
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2007)
In-hospital mortality [ Time Frame: Day 180 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 27, 2006)
In-hospital mortality
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2007)
  • Secondary outcomes : [ Time Frame: Day 180 ]
  • 90-day and 180-day mortality. [ Time Frame: Day 180 ]
  • Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation) [ Time Frame: Day 180 ]
  • Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8 [ Time Frame: Day 180 ]
  • Hospital length of stay. [ Time Frame: Day 180 ]
  • Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion [ Time Frame: Day 180 ]
  • Muscle weakness at discharge from intensive care unit, 90-day and 180-day [ Time Frame: Day 180 ]
  • Post traumatic stress disorders [ Time Frame: Day 180 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2006)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock
Official Title  ICMJE Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock
Brief Summary 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
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Septic Shock
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * COIITSS Study Investigators; Annane D, Cariou A, Maxime V, Azoulay E, D'honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santre 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 27, 2006)
508
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00320099
Other Study ID Numbers  ICMJE AOM04100
P040421
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Djillali Annane, AP-HP - University of Versailles SQY
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE University of Versailles
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Assistance Publique - Hôpitaux de Paris
Investigators  ICMJE
Study Chair: Djillali annane, MD, PhD Assistance Publique Hôpitaux de Paris - University of Versailles
PRS Account University of Versailles
Verification Date April 2010

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