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

University of Versailles

Status and phase: Completed; Phase 3

Conditions: Septic Shock

Treatments: Drug: recombinant human insulin; Drug: fludrocortisone; Drug: hydrocortisone; Drug: Hydrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT00320099

AOM04100

P040421

Details and patient eligibility

About

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

Full 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.

Enrollment: 508 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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508 participants in 4 patient groups

1

Active Comparator group

Description:

Hydrocortisone and convention glycemic control

Treatment:

Drug: hydrocortisone

2

Experimental group

Description:

Hydrocortisone and fludrocortisone and conventional glucose control

Treatment:

Drug: hydrocortisone

Drug: fludrocortisone

3

Experimental group

Description:

Hydrocortisone and intensive insulin therapy

Treatment:

Drug: hydrocortisone

Drug: recombinant human insulin

4

Experimental group

Description:

hydrocortisone, fludrocortisone and intensive insulin therapy

Treatment:

Drug: hydrocortisone

Drug: recombinant human insulin

Drug: fludrocortisone