Clinical trial NCT02361528: GM-CSF to Decrease ICU Acquired Infections
Official title: A Double-Blind, Randomized, Placebo-controlled Multicenter Trial of GRanulocyte-Macrophage Colony-stimulating Factor Administration to Decrease ICU Acquired Infections in Sepsis-induced ImmunoDepression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Septic Shock
Severe Sepsis
Keywords: Septic shock
Severe sepsis
GM-CSF
Immunosuppression
Hospital-acquired infections
ICU-acquired infections
HLA-DR
Monocytes
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2015-02-11
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of patients presenting at least one ICU-acquired infection at D28 or ICU discharge.
timeFrame: At Day 28 or ICU discharge.
Secondary outcomes:
measure: Incidence and incidence density of pneumonia, catheter related infections, and urinary tract infections
timeFrame: At Day 28 or ICU discharge.
measure: Survival at D28, end of ICU and hospital stay, and at 1 year
timeFrame: At Day 28 or ICU discharge.
measure: Organ failure free days
timeFrame: At Day 28 or ICU discharge.
measure: Number of serious adverse events and number of patients having presented at least one serious adverse event.
timeFrame: At Day 28 or ICU discharge.
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Hopital SUD
city: Clermont-ferrand
country: France
facility: CHU Estaing 1 place Lucie et Raymond Aubrac
city: Clermont-Ferrand
country: France
facility: CHU Gabriel MONTPIED
city: Grenoble
country: France
facility: CHU de Grenoble- Hopital Michallon
city: Grenoble
country: France
facility: CHU de Grenoble-Hopital Michallon
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Marseille
country: France
facility: APHM Hopital de la Timone
city: Marseille
country: France
facility: CHU la Conception
city: Marseille
country: France
facility: APHM Hopital Nord
city: Montpellier
country: France
facility: CHU Montpellier
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: CHU de Nantes
city: Nantes
country: France
facility: PTMC CHU de Nantes
city: Nîmes
country: France
facility: CHU de Nîmes
city: Pierre Benite
country: France
facility: Centre hospitalier Lyon Sud
city: Saint-Etienne
country: France
facility: CHU de Saint-Etienne
city: Saint-Etienne
country: France
facility: CHU Hopital Nord
Study officials:
References: