GM-CSF to Decrease ICU Acquired Infections (GRID)

A Double-Blind, Randomized, Placebo-controlled Multicenter Trial of GRanulocyte-Macrophage Colony-stimulating Factor Administration to Decrease ICU Acquired Infections in Sepsis-induced ImmunoDepression

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 Overview

• Status: Completed
• Conditions: Septic Shock; Severe Sepsis
• Intervention / Treatment: Drug: Sargramostim: Leukine (Genzyme USA); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU Amiens Hopital Sud
  • Clermont-Ferrand, France, 63003
    • Chu Gabriel Montpied
  • Clermont-Ferrand, France, 63003
    • CHU Estaing 1 place Lucie et Raymond Aubrac
  • Grenoble, France, 38043
    • CHU de Grenoble- Hopital Michallon
  • Grenoble, France, 38043
    • CHU de Grenoble-Hopital Michallon
  • Lyon, France, 69003
    • Hôpital Edouard Herriot
  • Lyon, France, 69317
    • Hopital de la croix rousse
  • Marseille, France, 13005
    • CHU la Conception
  • Marseille, France, 13005
    • APHM Hopital de la Timone
  • Marseille, France, 13915
    • APHM Hôpital Nord
  • Montpellier, France, 34295
    • Hopital Saint Eloi
  • Montpellier, France, 34295
    • CHU Montpellier
  • Nantes, France, 44093
    • CHU de Nantes
  • Nantes, France, 44093
    • PTMC CHU de Nantes
  • Nîmes, France, 30029
    • CHU de Nîmes
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Saint-Etienne, France, 42055
    • Chu de Saint-Etienne
  • Saint-Etienne, France, 42055
    • CHU Hopital Nord

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leukine; Sargramostim: Leukine (Genzyme USA), 125µg/m2 , once per day during 5 days, by subcutaneous route	Drug: Sargramostim: Leukine (Genzyme USA); Leukine: 125 µg/m² daily, subcutaneously, for 5 days.
Placebo Comparator: placebo; placebo, once per day during 5 days by subcutaneous route	Drug: Placebo; placebo subcutaneously, for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: February 6, 2015
• First Submitted That Met QC Criteria: February 10, 2015
• First Posted (Estimated): February 11, 2015

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Immunosuppression; Septic shock; Monocytes; GM-CSF; Severe sepsis; HLA-DR; Hospital-acquired infections; ICU-acquired infections
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Shock, Septic; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 2014.856; 2014-001894-15 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No