GRID: GM-CSF to Decrease ICU Acquired Infections

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT02361528

Collaborator

(none)

166

Enrollment

Locations

Arms

32.6

Actual Duration (Months)

9.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Severe Sepsis	Drug: Sargramostim: Leukine (Genzyme USA) Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 14, 2015

Actual Primary Completion Date :

Jun 1, 2018

Actual Study Completion Date :

Jun 1, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ICU patients presenting a severe sepsis or a septic shock associated with a sepsis-induced immunosuppression.

- 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).
- AND Sepsis-induced immunosuppression: reduced mHLA-DR levels (< 8,000 monoclonal antibodies (mAb) per cell at D3).

Exclusion Criteria:

- Therapeutic limitation
Evolutive hemopathy, neutropenia < 500/mm3, stemcell transplant
Solid tumor with on-going chemotherapy or radiotherapy
Human immunodeficiency virus (HIV) infection with CD 4 count < 200 cell/mm3
Immunosuppressive treatment (including corticosteroid at immunosuppressive dose : > 10 mg equivalent prednisolone and cumulative dose > 700 mg)
Primary immunodeficiency .
Extra corporeal circulation within one month
Recent cardio-pulmonary resuscitation (within the current clinical episode)
Patients admitted in ICU for extensive burns
Contraindications to sargramostim
Pregnant or lactating women
Participation to another interventional study.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Amiens Hopital SUD	Amiens	France	80054
2	CHU Estaing 1 place Lucie et Raymond Aubrac	Clermont-ferrand	France	63003
3	CHU Gabriel MONTPIED	Clermont-Ferrand	France	63003
4	CHU de Grenoble- Hopital Michallon	Grenoble	France	38043
5	CHU de Grenoble-Hopital Michallon	Grenoble	France	38043
6	Hopital Edouard Herriot	Lyon	France	69003
7	Hopital de la Croix Rousse	Lyon	France	69317
8	APHM Hopital de la Timone	Marseille	France	13005
9	CHU la Conception	Marseille	France	13005
10	APHM Hopital Nord	Marseille	France	13915
11	CHU Montpellier	Montpellier	France	34295
12	Hopital Saint Eloi	Montpellier	France	34295
13	CHU de Nantes	Nantes	France	44093
14	PTMC CHU de Nantes	Nantes	France	44093
15	CHU de Nîmes	Nîmes	France	30029
16	Centre hospitalier Lyon Sud	Pierre Benite	France	69495
17	CHU de Saint-Etienne	Saint-Etienne	France	42055
18	CHU Hopital Nord	Saint-Etienne	France	42055