Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock - Full Text View

Sponsor:	University of Versailles
Collaborator:	Assistance Publique - Hôpitaux de Paris
Information provided by:	University of Versailles
ClinicalTrials.gov Identifier:	NCT00320099

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 III

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:

MedlinePlus related topics: Diabetes Medicines Shock

Drug Information available for: Hydrocortisone acetate Hydrocortisone Insulin Insulin beef Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Hydrocortisone 21-sodium succinate Fludrocortisone Hydrocortisone cypionate Fludrocortisone 21-acetate Cortisol succinate Cortisol 21-phosphate

U.S. FDA Resources

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

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 Saint Louis
Paris, France, 75
hôpital Cochin
Paris, France
Hôpital Bichat Claude Bernard
Paris, France
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:

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, Mayaud 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.

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 - French Health Products Safety Agency

Keywords provided by University of Versailles:

septic shock
adrenal insufficiency
glucose control
mineralocorticoids

Additional relevant MeSH terms:

Shock
Shock, Septic
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Cortisol succinate
Hydrocortisone acetate

Fludrocortisone
Hydrocortisone
Insulin
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012