Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock

Septic Shock Clinical Trial

— COIITSS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00320099
• Other study ID #: AOM04100
• Secondary ID: P040421
• Status: Completed
• Phase: Phase 3
• First received: April 27, 2006
• Last updated: April 5, 2010
• Start date: January 2006
• Est. completion date: February 2009

Study information

• Verified date: April 2010
• Source: University of Versailles
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: February 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• recombinant human insulin
intensive insulin therapy as a continuous infusion to maintain blood glucose levels between 4 and 6 mmol/l
• hydrocortisone
50 mg as iv bolus every 6 hours for 7 days
• fludrocortisone
50 µg once a day via a nasogastric tube for seven days
• Hydrocortisone
hydrocortisone 50mg q6 for 7 days

Locations

Country	Name	City	State
France	Hôpital Avicenne	Bobigny
France	Hôpital Jean Verdier	Bondy
France	CHU Grenoble	Grenoble
France	Hôpital central	Nancy
France	Hôpital Bichat Claude Bernard	Paris
France	hôpital Cochin	Paris
France	Hôpital Saint Louis	Paris
France	Hôpital Delafontaine	Saint Denis

Sponsors (2)

Lead Sponsor	Collaborator
University of Versailles	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

COIITSS Study Investigators, Annane D, Cariou A, Maxime V, Azoulay E, D'honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santré C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec'h C, Mayaux J, Lejeune J, Chevret S. Corticosteroid treatment — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In-hospital mortality		Day 180	Yes
Secondary	Secondary outcomes :		Day 180	Yes
Secondary	90-day and 180-day mortality.		Day 180	Yes
Secondary	Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation)		Day 180	Yes
Secondary	Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8		Day 180	No
Secondary	Hospital length of stay.		Day 180	No
Secondary	Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion		Day 180	Yes
Secondary	Muscle weakness at discharge from intensive care unit, 90-day and 180-day		Day 180	Yes
Secondary	Post traumatic stress disorders		Day 180	Yes