GM-CSF to Decrease ICU Acquired Infections

Hospices Civils de Lyon166 enrolled

Overview

The concept of acquired immunodeficiency after a first severe infection in the ICU is widely described in the literature. There is a dual risk: increased mortality and increased secondary infections. Several approaches of immunostimulatory treatments have been proposed in the literature. The treatment proposed by this study consists of the administration of Granulocyte-macrophage colony-stimulating factor (GM-CSF), colony stimulating factor widely used particularly in the USA where it is marketed. A phase 2 clinical trial was conducted in Germany in 2009. The main objective is to measure the incidence of ICU-acquired infections in 2 groups of patients treated by GM-CSF or placebo. ICU patients at risk are defined as surviving at D3 from a severe sepsis or septic shock and presenting a sepsis associated immunodepression. The detection of immunosuppressed patients will be achieved by measuring the HLA-DR (Human Leucocyte Antigen DR)with a threshold of less to 8000 sites. Our hypothesis is that the number of secondary infections (primary endpoint) will be significantly reduced in the treated group.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

166

Conditions

Septic Shock Severe Sepsis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: ICU patients presenting a severe sepsis or a septic shock associated with a sepsis-induced immunosuppression. 1. \- Severe sepsis OR septic shock defined by the association of: at least 2 criteria of Systemic Inflammation Response Syndrome (SIRS) a clinically or microbiologically defined infection and respectively at least one organ failure (level ≥ 2 in one organ failure of the SOFA score) OR the need of a vasopressor treatment (epinephrine or norepinephrine ≥ 0,25mg/kg/min for at least 6 hrs to maintain a systolic pressure ≥ 90 mmHg or a mean arterial pressure ≥ 65 mmHg). 2. \- AND Sepsis-induced immunosuppression: reduced mHLA-DR levels (\< 8,000 monoclonal antibodies (mAb) per cell at D3). Exclusion Criteria: 1. \- Therapeutic limitation 2. Evolutive hemopathy, neutropenia \< 500/mm3, stemcell transplant 3. Solid tumor with on-going chemotherapy or radiotherapy 4. Human immunodeficiency virus (HIV) infection with CD 4 count \< 200 cell/mm3 5. Immunosuppressive treatment (including corticosteroid at immunosuppressive dose : \> 10 mg equivalent prednisolone and cumulative dose \> 700 mg) 6. Primary immunodeficiency . 7. Extra corporeal circulation within one month 8. Recent cardio-pulmonary resuscitation (within the current clinical episode) 9. Patients admitted in ICU for extensive burns 10. Contraindications to sargramostim 11. Pregnant or lactating women 12. Participation to another interventional study.

Locations (18)

CHU Amiens Hopital SUD

Amiens, France

CHU Estaing 1 place Lucie et Raymond Aubrac

Clermont-Ferrand, France

CHU Gabriel MONTPIED

Clermont-Ferrand, France

CHU de Grenoble- Hopital Michallon

Grenoble, France

CHU de Grenoble-Hopital Michallon

Grenoble, France

Hopital Edouard Herriot

Lyon, France

Hopital de la Croix Rousse

Lyon, France

APHM Hopital de la Timone

Marseille, France

CHU la Conception

Marseille, France

APHM Hopital Nord

Marseille, France

...and 8 more locations

Outcomes

Primary Outcomes

Number of patients presenting at least one ICU-acquired infection at D28 or ICU discharge.

ICU-acquired infections will be recorded in accordance with the definitions of the European CDC used in the French network of IAI surveillance Rea Raisin. An independent committee blinded to treatment group will ensure the classification of hospital-acquired infections.