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.

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)