GM-CSF to Decrease ICU Acquired Infections

NCT ID: NCT02361528

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-14
• Study Completion Date: 2018-06-01

Brief Summary

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.

Conditions

Septic Shock; Severe Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Leukine

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

Group Type: EXPERIMENTAL

Sargramostim: Leukine (Genzyme USA)

Intervention Type: DRUG

Leukine: 125 µg/m² daily, subcutaneously, for 5 days.

placebo

placebo, once per day during 5 days by subcutaneous route

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo subcutaneously, for 5 days

Interventions

Sargramostim: Leukine (Genzyme USA)

Leukine: 125 µg/m² daily, subcutaneously, for 5 days.

Intervention Type: DRUG

Placebo

placebo subcutaneously, for 5 days

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

CHU Montpellier

Montpellier, , France

Hopital Saint Eloi

Montpellier, , France

CHU de Nantes

Nantes, , France

PTMC CHU de Nantes

Nantes, , France

CHU de Nîmes

Nîmes, , France

Centre hospitalier Lyon Sud

Pierre-Bénite, , France

CHU de Saint-Etienne

Saint-Etienne, , France

CHU Hopital Nord

Saint-Etienne, , France

Countries

France

References

Vacheron CH, Lepape A, Venet F, Monneret G, Gueyffier F, Boutitie F, Vallin H, Schwebel C, Maucort-Boulch D, Friggeri A; GRID Study Group. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients presenting sepsis-induced immunosuppression: The GRID randomized controlled trial. J Crit Care. 2023 Dec;78:154330. doi: 10.1016/j.jcrc.2023.154330. Epub 2023 May 31.

Reference Type: BACKGROUND

PMID: 37267804 (View on PubMed)

Other Identifiers

2014.856

Identifier Type: -

Identifier Source: org_study_id