GM-CSF to Decrease ICU Acquired Infections

NCT02361528 | Completed Phase 3 DMC

• 1 other identifier: 2014.856
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 18

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

Keywords

Septic shock; Severe sepsis; GM-CSF; Immunosuppression; Hospital-acquired infections; ICU-acquired infections; HLA-DR; Monocytes

Outcome Measures

Primary Outcomes (1)

• 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.

  At Day 28 or ICU discharge.

Secondary Outcomes (4)

• Incidence and incidence density of pneumonia, catheter related infections, and urinary tract infections

  At Day 28 or ICU discharge.

• Survival at D28, end of ICU and hospital stay, and at 1 year

  At Day 28 or ICU discharge.

• Organ failure free days

  At Day 28 or ICU discharge.

• Number of serious adverse events and number of patients having presented at least one serious adverse event.

  At Day 28 or ICU discharge.

Study Arms (2)

Leukine

EXPERIMENTAL

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

Drug: Sargramostim: Leukine (Genzyme USA)

placebo

PLACEBO COMPARATOR

placebo, once per day during 5 days by subcutaneous route

Drug: Placebo

Interventions

Sargramostim: Leukine (Genzyme USA) DRUG

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

Leukine

Placebo DRUG

placebo subcutaneously, for 5 days

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ICU patients presenting a severe sepsis or a septic shock associated with a sepsis-induced immunosuppression.
• \- 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).
• \- AND Sepsis-induced immunosuppression: reduced mHLA-DR levels (\< 8,000 monoclonal antibodies (mAb) per cell at D3).

You may not qualify if:

• \- Therapeutic limitation
• Evolutive hemopathy, neutropenia \< 500/mm3, stemcell transplant
• Solid tumor with on-going chemotherapy or radiotherapy
• Human immunodeficiency virus (HIV) infection with CD 4 count \< 200 cell/mm3
• Immunosuppressive treatment (including corticosteroid at immunosuppressive dose : \> 10 mg equivalent prednisolone and cumulative dose \> 700 mg)
• Primary immunodeficiency .
• Extra corporeal circulation within one month
• Recent cardio-pulmonary resuscitation (within the current clinical episode)
• Patients admitted in ICU for extensive burns
• Contraindications to sargramostim
• Pregnant or lactating women
• Participation to another interventional study.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (18)

CHU Amiens Hopital SUD

Amiens, 80054, France

Location

CHU Estaing 1 place Lucie et Raymond Aubrac

Clermont-Ferrand, 63003, France

Location

CHU Gabriel MONTPIED

Clermont-Ferrand, 63003, France

Location

CHU de Grenoble- Hopital Michallon

Grenoble, 38043, France

Location

CHU de Grenoble-Hopital Michallon

Grenoble, 38043, France

Location

Hopital Edouard Herriot

Lyon, 69003, France

Location

Hopital de la Croix Rousse

Lyon, 69317, France

Location

APHM Hopital de la Timone

Marseille, 13005, France

Location

CHU la Conception

Marseille, 13005, France

Location

APHM Hopital Nord

Marseille, 13915, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

CHU de Nantes

Nantes, 44093, France

Location

PTMC CHU de Nantes

Nantes, 44093, France

Location

CHU de Nîmes

Nîmes, 30029, France

Location

Centre hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Saint-Etienne

Saint-Etienne, 42055, France

Location

CHU Hopital Nord

Saint-Etienne, 42055, France

Location

Related Publications (1)

• 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.

  PMID: 37267804 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2015
• First Posted: February 11, 2015
• Study Start: September 14, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: September 3, 2025

Record last verified: 2025-08

Locations

FR (18)