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GM-CSF to Decrease ICU Acquired Infections (GRID)

Primary Purpose

Septic Shock, Severe Sepsis

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Sargramostim: Leukine (Genzyme USA)
Placebo
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Septic shock, Severe sepsis, GM-CSF, Immunosuppression, Hospital-acquired infections, ICU-acquired infections, HLA-DR, Monocytes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU Amiens Hopital SUD
  • CHU Estaing 1 place Lucie et Raymond Aubrac
  • CHU Gabriel MONTPIED
  • CHU de Grenoble- Hopital Michallon
  • CHU de Grenoble-Hopital Michallon
  • Hopital Edouard Herriot
  • Hopital de la Croix Rousse
  • APHM Hopital de la Timone
  • CHU la Conception
  • APHM Hopital Nord
  • CHU Montpellier
  • Hopital Saint Eloi
  • CHU de Nantes
  • PTMC CHU de Nantes
  • CHU de Nîmes
  • Centre hospitalier Lyon Sud
  • CHU de Saint-Etienne
  • CHU Hopital Nord

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Leukine

placebo

Arm Description

Sargramostim: Leukine (Genzyme USA), 125µg/m2 , once per day during 5 days, by subcutaneous route

placebo, once per day during 5 days by subcutaneous route

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incidence and incidence density of pneumonia, catheter related infections, and urinary tract infections
Survival at D28, end of ICU and hospital stay, and at 1 year
Organ failure free days
Number of serious adverse events and number of patients having presented at least one serious adverse event.

Full Information

First Posted
February 6, 2015
Last Updated
October 31, 2019
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02361528
Brief Title
GM-CSF to Decrease ICU Acquired Infections
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
September 14, 2015 (Actual)
Primary Completion Date
June 1, 2018 (Actual)
Study Completion Date
June 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock, Severe Sepsis
Keywords
Septic shock, Severe sepsis, GM-CSF, Immunosuppression, Hospital-acquired infections, ICU-acquired infections, HLA-DR, Monocytes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
166 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Leukine
Arm Type
Experimental
Arm Description
Sargramostim: Leukine (Genzyme USA), 125µg/m2 , once per day during 5 days, by subcutaneous route
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo, once per day during 5 days by subcutaneous route
Intervention Type
Drug
Intervention Name(s)
Sargramostim: Leukine (Genzyme USA)
Intervention Description
Leukine: 125 µg/m² daily, subcutaneously, for 5 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo subcutaneously, for 5 days
Primary Outcome Measure Information:
Title
Number of patients presenting at least one ICU-acquired infection at D28 or ICU discharge.
Description
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.
Time Frame
At Day 28 or ICU discharge.
Secondary Outcome Measure Information:
Title
Incidence and incidence density of pneumonia, catheter related infections, and urinary tract infections
Time Frame
At Day 28 or ICU discharge.
Title
Survival at D28, end of ICU and hospital stay, and at 1 year
Time Frame
At Day 28 or ICU discharge.
Title
Organ failure free days
Time Frame
At Day 28 or ICU discharge.
Title
Number of serious adverse events and number of patients having presented at least one serious adverse event.
Time Frame
At Day 28 or ICU discharge.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
CHU Amiens Hopital SUD
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHU Estaing 1 place Lucie et Raymond Aubrac
City
Clermont-ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
CHU Gabriel MONTPIED
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
CHU de Grenoble- Hopital Michallon
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHU de Grenoble-Hopital Michallon
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hopital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
Hopital de la Croix Rousse
City
Lyon
ZIP/Postal Code
69317
Country
France
Facility Name
APHM Hopital de la Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
CHU la Conception
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
APHM Hopital Nord
City
Marseille
ZIP/Postal Code
13915
Country
France
Facility Name
CHU Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Saint Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
PTMC CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU de Nîmes
City
Nîmes
ZIP/Postal Code
30029
Country
France
Facility Name
Centre hospitalier Lyon Sud
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
CHU de Saint-Etienne
City
Saint-Etienne
ZIP/Postal Code
42055
Country
France
Facility Name
CHU Hopital Nord
City
Saint-Etienne
ZIP/Postal Code
42055
Country
France

12. IPD Sharing Statement

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GM-CSF to Decrease ICU Acquired Infections

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