Septic Shock
Conditions
Keywords
septic shock, adrenal insufficiency, glucose control, mineralocorticoids
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.
Interventions
intensive insulin therapy as a continuous infusion to maintain blood glucose levels between 4 and 6 mmol/l
DRUGhydrocortisone
50 mg as iv bolus every 6 hours for 7 days
DRUGfludrocortisone
50 µg once a day via a nasogastric tube for seven days
DRUGHydrocortisone
hydrocortisone 50mg q6 for 7 days
Sponsors
Assistance Publique - Hôpitaux de Paris
University of Versailles
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In-hospital mortality | Day 180 |
Secondary
| Measure | Time frame |
|---|---|
| 90-day and 180-day mortality. | Day 180 |
| Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation) | Day 180 |
| Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8 | Day 180 |
| Secondary outcomes : | Day 180 |
| Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion | Day 180 |
| Muscle weakness at discharge from intensive care unit, 90-day and 180-day | Day 180 |
| Post traumatic stress disorders | Day 180 |
| Hospital length of stay. | Day 180 |
Countries
France
Outcome results
None listed