GM-CSF to Decrease ICU Acquired Infections

Phase 3

Completed

• Conditions: Septic Shock; Severe Sepsis
• Interventions: Drug: Placebo

• Registration Number: NCT02361528
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-02-06
• Study First Submitted QC: 2015-02-10
• Study First Posted: 2015-02-11
• Study Start: 2015-09-14
• Primary Completion: 2018-06-01
• Study Completion: 2018-06-01
• Status Verified: 2018-09
• Last Update Submitted: 2019-10-31
• Last Update Posted: 2019-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 166

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	placebo, once per day during 5 days by subcutaneous route

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (18)

Hopital Edouard Herriot; 🇫🇷 Lyon, France

APHM Hopital Nord; 🇫🇷 Marseille, France

CHU de Nantes; 🇫🇷 Nantes, France

CHU Montpellier; 🇫🇷 Montpellier, France

PTMC CHU de Nantes; 🇫🇷 Nantes, France

CHU de Saint-Etienne; 🇫🇷 Saint-Etienne, France

Hopital de la Croix Rousse; 🇫🇷 Lyon, France

CHU la Conception; 🇫🇷 Marseille, France

CHU de Nîmes; 🇫🇷 Nîmes, France

Centre hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

CHU Amiens Hopital SUD; 🇫🇷 Amiens, France

CHU de Grenoble- Hopital Michallon; 🇫🇷 Grenoble, France

CHU Estaing 1 place Lucie et Raymond Aubrac; 🇫🇷 Clermont-ferrand, France

CHU Gabriel MONTPIED; 🇫🇷 Clermont-Ferrand, France

APHM Hopital de la Timone; 🇫🇷 Marseille, France

CHU de Grenoble-Hopital Michallon; 🇫🇷 Grenoble, France

Hopital Saint Eloi; 🇫🇷 Montpellier, France

CHU Hopital Nord; 🇫🇷 Saint-Etienne, France