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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
  Purpose

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


Condition Intervention Phase
Septic Shock
Drug: recombinant human insulin
Drug: hydrocortisone
Drug: fludrocortisone
Drug: Hydrocortisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock

Resource links provided by NLM:


Further study details as provided by University of Versailles:

Primary Outcome Measures:
  • In-hospital mortality [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 508
Study Start Date: January 2006
Study Completion Date: February 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Hydrocortisone and convention glycemic control
Drug: hydrocortisone
50 mg as iv bolus every 6 hours for 7 days
Drug: Hydrocortisone
hydrocortisone 50mg q6 for 7 days
Experimental: 2
Hydrocortisone and fludrocortisone and conventional glucose control
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
Experimental: 3
Hydrocortisone and intensive insulin therapy
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
Experimental: 4
hydrocortisone, fludrocortisone and intensive insulin therapy
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

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.

  Eligibility

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

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)
  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: NCT00320099

Locations
France
Hôpital Avicenne
Bobigny, France
Hôpital Jean Verdier
Bondy, France
CHU Grenoble
Grenoble, France
Hôpital central
Nancy, France
Hôpital Bichat Claude Bernard
Paris, France
hôpital Cochin
Paris, France
Hôpital Saint Louis
Paris, France, 75
Hôpital Delafontaine
Saint Denis, France, 93
Sponsors and Collaborators
University of Versailles
Assistance Publique - Hôpitaux de Paris
Investigators
Study Chair: Djillali annane, MD, PhD Assistance Publique Hôpitaux de Paris - University of Versailles
  More Information

Publications:
Responsible Party: Djillali Annane, AP-HP - University of Versailles SQY
ClinicalTrials.gov Identifier: NCT00320099     History of Changes
Other Study ID Numbers: AOM04100, P040421
Study First Received: April 27, 2006
Last Updated: April 5, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University of Versailles:
septic shock
adrenal insufficiency
glucose control
mineralocorticoids

Additional relevant MeSH terms:
Shock
Shock, Septic
Infection
Inflammation
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Cortisol succinate
Fludrocortisone
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Insulin
Insulin, Globin Zinc
Anti-Inflammatory Agents
Dermatologic Agents
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014