Clinical trial NCT00320099: Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock
Official title: Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Septic Shock
Keywords: septic shock
adrenal insufficiency
glucose control
mineralocorticoids
Lead sponsor: University of Versailles
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
First posted: 2006-05-03
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: In-hospital mortality
timeFrame: Day 180
Secondary outcomes:
measure: Secondary outcomes :
timeFrame: Day 180
measure: 90-day and 180-day mortality.
timeFrame: Day 180
measure: Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation)
timeFrame: Day 180
measure: Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8
timeFrame: Day 180
measure: Hospital length of stay.
timeFrame: Day 180
measure: Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion
timeFrame: Day 180
measure: Muscle weakness at discharge from intensive care unit, 90-day and 180-day
timeFrame: Day 180
measure: Post traumatic stress disorders
timeFrame: Day 180
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Grenoble
country: France
facility: CHU Grenoble
city: Nancy
country: France
facility: Hôpital central
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Bichat Claude Bernard
city: Paris
country: France
facility: hôpital Cochin
city: Saint Denis
country: France
facility: Hôpital Delafontaine
Study officials:
affiliation: Assistance Publique Hôpitaux de Paris - University of Versailles
name: Djillali annane, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.