GM-CSF to Decrease ICU Acquired Infections

Septic Shock Clinical Trial

— GRID  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02361528
• Other study ID #: 2014.856
• Status: Completed
• Phase: Phase 3
• Start date: September 14, 2015
• Est. completion date: June 1, 2018

Study information

• Verified date: September 2018
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: June 1, 2018
• Est. primary completion date: June 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infection
• Sepsis
• Septic Shock
• Severe Sepsis
• Shock, Septic

Intervention

Drug:
• Sargramostim: Leukine (Genzyme USA)
Leukine: 125 µg/m² daily, subcutaneously, for 5 days.
• Placebo
placebo subcutaneously, for 5 days

Locations

Country	Name	City	State
France	CHU Amiens Hopital SUD	Amiens
France	CHU Estaing 1 place Lucie et Raymond Aubrac	Clermont-ferrand
France	CHU Gabriel MONTPIED	Clermont-Ferrand
France	CHU de Grenoble- Hopital Michallon	Grenoble
France	CHU de Grenoble-Hopital Michallon	Grenoble
France	Hopital de la Croix Rousse	Lyon
France	Hopital Edouard Herriot	Lyon
France	APHM Hopital de la Timone	Marseille
France	APHM Hopital Nord	Marseille
France	CHU la Conception	Marseille
France	CHU Montpellier	Montpellier
France	Hopital Saint Eloi	Montpellier
France	CHU de Nantes	Nantes
France	PTMC CHU de Nantes	Nantes
France	CHU de Nîmes	Nîmes
France	Centre hospitalier Lyon Sud	Pierre Benite
France	CHU de Saint-Etienne	Saint-Etienne
France	CHU Hopital Nord	Saint-Etienne

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence and incidence density of pneumonia, catheter related infections, and urinary tract infections		At Day 28 or ICU discharge.
Secondary	Survival at D28, end of ICU and hospital stay, and at 1 year		At Day 28 or ICU discharge.
Secondary	Organ failure free days		At Day 28 or ICU discharge.
Secondary	Number of serious adverse events and number of patients having presented at least one serious adverse event.		At Day 28 or ICU discharge.