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

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

• 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 ]
  

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.