Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock

Condition(s) targeted: Septic Shock

Intervention: recombinant human insulin (Drug); hydrocortisone (Drug); fludrocortisone (Drug); Hydrocortisone (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Versailles

Official(s) and/or principal investigator(s):
Djillali annane, MD, PhD, Study Chair, Affiliation: Assistance Publique Hôpitaux de Paris - University of Versailles

Overall contact:
Djillali annane, MD, PhD, Phone: 331 47 10 77 87, Email: djillali.annane@rpc.aphp.fr

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

Official title: Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock

Study design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome: In-hospital mortality

Secondary outcome:

Secondary outcomes :

90-day and 180-day mortality.

Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation)

Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8

Hospital length of stay.

Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion

Muscle weakness at discharge from intensive care unit, 90-day and 180-day

Post traumatic stress disorders

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

Djillali annane, MD, PhD, Phone: 331 47 10 77 87, Email: djillali.annane@rpc.aphp.fr

Hôpital Delafontaine, Saint Denis 93, France; Recruiting
Christophe ADRIE
Christophe ADRIE, Principal Investigator

Hôpital Saint Louis, Paris 75, France; Recruiting
Elie Azoulay
Elie Azoulay, Principal Investigator

hôpital Cochin, Paris, France; Recruiting
Alain Cariou
Alain Cariou, Principal Investigator

Hôpital Avicenne, Bobigny, France; Recruiting
Yves Cohen
Yves Cohen, Principal Investigator

Hôpital Bichat Claude Bernard, Paris, France; Recruiting
Michel Wolf
Michel Wolf, Principal Investigator

Hôpital central, Nancy, France; Recruiting
Pierre Edouard Bollaert
Pierre Edouard Bollaert, Principal Investigator

Hôpital Jean Verdier, Bondy, France; Recruiting
Gilles Dhonneur
Gilles Dhonneur, Principal Investigator

CHU Grenoble, Grenoble, France; Recruiting
Jean François Timsit
Jean François Timsit, Principal Investigator

Starting date: January 2006
Ending date: January 2009
Last updated: June 17, 2008