Following of Myeloid-derived Suppressor Cells (MDSC) in Severe Sepsis: What Relationship With Systemic Inflammatory Syndrome?

Terminated

• Conditions: Inflammatory Response Syndrome, Systemic; Severe Sepsis
• Interventions: Biological: Residue of blood further to preoperative workup; Biological: Residue of blood further to NFS; Biological: Bone marrow collected during a myelogram carried out for hematological pathology workup; Biological: Bone marrow collected during myelogram routinely performed during hospitalization in ICU

• Registration Number: NCT02903082
• Lead Sponsor: University Hospital, Limoges

Brief Summary

Sepsis remains a major cause of death in developed countries. A better understanding of the mechanisms involved in the regulation of inflammatory and immune response of patients with severe sepsis is an important step that could open the way for new therapeutic approaches.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2016-09-02
• Study First Submitted QC: 2016-09-12
• Study First Posted: 2016-09-16
• Primary Completion: 2018-01
• Study Completion: 2018-01
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-25
• Last Update Posted: 2019-01-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

• Patient ≥18 years old

• Patient with two criteria of systemic inflammatory response syndrome and one of the four following criteria within 24 hours of hospitalization in ICU:

  • Lactate >4 mmol/L
  • PaO2 / FiO2 <200 in the presence of lung disease as infectious source
  • Vasopressor: adrenaline or noradrenaline ≥0.25 µg/kg/min for at least 6 hours to maintain a systolic blood pressure ≥90 mmHg or mean arterial pressure ≥65 mmHg
  • Thrombocytopenia linked to sepsis with platelet count <100,000 / ml or a decrease ≤50% within 48 hours

Exclusion Criteria

• Pregnancy
• progressive solid cancer
• HIV infection
• History of blood or inflammatory disease
• long-term immunosuppressive treatment
• Prior episode of Sepsis in the previous month
• Chronic Dialysis Patient
• Patient under guardianship
• Patient not affiliated with a social security system

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control	Residue of blood further to preoperative workup	10 Patients hospitalized for a hematologic pathology workup considered normal by two haematologists and 10 patients hospitalized for a preoperative workup.
Control	Bone marrow collected during a myelogram carried out for hematological pathology workup	10 Patients hospitalized for a hematologic pathology workup considered normal by two haematologists and 10 patients hospitalized for a preoperative workup.
Case	Residue of blood further to NFS	Patient hospitalized in intensive care for sepsis evolving for less than 48 hours with two criteria of systemic inflammatory response syndrome
Case	Bone marrow collected during myelogram routinely performed during hospitalization in ICU	Patient hospitalized in intensive care for sepsis evolving for less than 48 hours with two criteria of systemic inflammatory response syndrome

Primary Outcome Measures

Name	Time	Method
Change in Peripheral Blood MDSC concentration during ICU hospitalization for Severe Sepsis	Average 30 days - Patients will be followed up until hospital discharge	Number of patients showing an increase of Myeloid derived suppressive cells from baseline at Day 30.; Kinetic of Myeloid derived suppressive cells through weekly measures of Absolute Cell Counts (using flow cytometry)

Secondary Outcome Measures

Name	Time	Method
MDSCs presence in the blood and bone marrow.	Day 0	Concentration of MDSC in the blood determined by flow cytometry
Assessment of MDSC functional status	Day 0 vs Days 3, 7, 14, 21, 28	Inhibition of T cell proliferation capacity (co-culture assay in vitro)MDSC cell culture
Incidence of hospital acquired secondary infections at Day 28	Day 28	Incidence of hospital acquired secondary infections at Day 28
Immuno- inflammatory status	Day 0, Day3, Day 7 and once a week until the intensive care unit discharge	Pro-inflammatory cytokines determined by flow cytometry
Assessment of MDSC specific gene expressions	Day 0 vs Days 3, 7, 14, 21, 28	Measurement of MDSC activation by real-time qRT-PCRMDSC cell culture
Mortality	Day 28 and Day 90	Dead or alive
SOFA score	Day 0, Day3, Day 7 and once a week until the intensive care unit discharge	Calculating of SOFA score

Trial Locations

Locations (1)

CHU de LIMOGES; 🇫🇷 Limoges, France