GM-CSF to Decrease ICU Acquired Infections

Conditions

Septic Shock, Severe Sepsis

Keywords

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

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.

Estelle Peronnet, Sophie Blein, Fabienne Venet, Elisabeth Cerrato, Aurore Fleurie et al. (16 authors)

Critical Care Medicine2023-03-1411 citations

10.1097/ccm.0000000000005832

Monocyte HLA-DR Assessment by a Novel Point-of-Care Device Is Feasible for Early Identification of ICU Patients With Complicated Courses—A Proof-of-Principle Study

Sandra Tamulyte, Jessica Kopplin, Thorsten Brenner, Markus Weigand, Florian Uhle

Frontiers in Immunology2019-03-1231 citations

10.3389/fimmu.2019.00432

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study.

Conway Morris A, Datta D, Shankar-Hari M, Stephen J, Weir CJ, Rennie J, Antonelli J, Bateman A, Warner N, Judge K, Keenan J, Wang A, Burpee T, Brown KA, Lewis SM, Mare T, Roy AI, Hulme G, Dimmick I, Rossi AG, Simpson AJ, Walsh TS.

2018-05-0190 citations

10.1007/s00134-018-5247-0

Occurrence of marked sepsis-induced immunosuppression in pediatric septic shock: a pilot study.

Remy S, Kolev-Descamps K, Gossez M, Venet F, Demaret J, Javouhey E, Monneret G.

2018-03-1331 citations

10.1186/s13613-018-0382-x

Interventions

DRUGSargramostim: Leukine (Genzyme USA)

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

DRUGPlacebo

placebo subcutaneously, for 5 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of patients presenting at least one ICU-acquired infection at D28 or ICU discharge.	At Day 28 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.

Secondary

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.

Countries

France

Outcome results

None listed