Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock

Phase 3

Completed

• Conditions: Septic Shock
• Interventions: Drug: recombinant human insulin; Drug: Hydrocortisone; Drug: fludrocortisone

• Registration Number: NCT00320099
• Lead Sponsor: University of Versailles

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.

Study Timeline

• Study Start: 2006-01
• Study First Submitted: 2006-04-27
• Study First Submitted QC: 2006-04-27
• Study First Posted: 2006-05-03
• Primary Completion: 2009-01
• Study Completion: 2009-02
• Status Verified: 2010-04
• Last Update Submitted: 2010-04-05
• Last Update Posted: 2010-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 508

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
3	recombinant human insulin	Hydrocortisone and intensive insulin therapy
4	recombinant human insulin	hydrocortisone, fludrocortisone and intensive insulin therapy
1	Hydrocortisone	Hydrocortisone and convention glycemic control
2	Hydrocortisone	Hydrocortisone and fludrocortisone and conventional glucose control
2	fludrocortisone	Hydrocortisone and fludrocortisone and conventional glucose control
3	Hydrocortisone	Hydrocortisone and intensive insulin therapy
4	Hydrocortisone	hydrocortisone, fludrocortisone and intensive insulin therapy
4	fludrocortisone	hydrocortisone, fludrocortisone and intensive insulin therapy

Primary Outcome Measures

Name	Time	Method
In-hospital mortality	Day 180

Secondary Outcome Measures

Name	Time	Method
Secondary outcomes :	Day 180
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
Hospital length of stay.	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

Trial Locations

Locations (8)

Hôpital Jean Verdier; 🇫🇷 Bondy, France

Hôpital central; 🇫🇷 Nancy, France

Hôpital Avicenne; 🇫🇷 Bobigny, France

CHU Grenoble; 🇫🇷 Grenoble, France

Hôpital Saint Louis; 🇫🇷 Paris, France

hôpital Cochin; 🇫🇷 Paris, France

Hôpital Bichat Claude Bernard; 🇫🇷 Paris, France

Hôpital Delafontaine; 🇫🇷 Saint Denis, France