GM-CSF to Decrease ICU Acquired Infections (GRID)

Civil Hospices of Lyon

Status and phase: Completed; Phase 3

Conditions: Severe Sepsis; Septic Shock

Treatments: Drug: Sargramostim: Leukine (Genzyme USA); Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02361528

2014.856

Details and patient eligibility

About

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.

Enrollment: 166 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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166 participants in 2 patient groups, including a placebo group

Leukine

Experimental group

Description:

Sargramostim: Leukine (Genzyme USA), 125µg/m2 , once per day during 5 days, by subcutaneous route

Treatment:

Drug: Sargramostim: Leukine (Genzyme USA)

placebo

Placebo Comparator group

Description:

placebo, once per day during 5 days by subcutaneous route

Treatment:

Drug: Placebo