Platelet-associated Inflammation in Severe Sepsis (PlatISSep)

Sepsis represents a serious public health issue characterized by a complex inflammatory response. In addition to their hemostatic role, platelets display inflammatory functions by secreting a variety of immunomodulatory factors and interacting with circulating immune cells. The investigators postulate that, in severe sepsis, platelets become activated and release amounts of different soluble inflammatory molecules that contribute to sepsis-associated inflammation. First, the investigators propose to assess whether severe sepsis impairs the ability of platelets to release soluble CD40L (sCD40L), an powerful platelet-derived immunomodulatory molecule, in ICU patients with S. aureus documented infection, ICU patients with documented infection involving other bacterial species, compared to ICU patients with inflammation of noninfectious origin and healthy blood donors. Then, the investigators wish to assess whether the bacterial species affects the release of platelet sCD40L and by an extensive screening of platelet soluble factors, the investigators propose to set up profiles of inflammatory molecules associated with the type of infection. Finally, the investigators will analyze platelets' activation state and their association with circulating immune, according to the type of infection. Therefore, this project is expected to assess to which extent the platelet inflammatory function is super-activated in severe sepsis and to identify new platelet-related biomarkers of sepsis.

Study Overview

• Status: Completed
• Conditions: Severe Sepsis
• Intervention / Treatment: Other: Blood samples

• Study Type: Observational
• Enrollment (Actual): 127

Contacts and Locations

Study Locations

• France
  • Saint Etienne, France, 42055
    • CHU SAINT-ETIENNE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe sepsis

Description

Inclusion criteria

Common inclusion criteria for ICU patients : Signed informed consent, Patient affiliated or entitled to a social security, aged over 18 years,

• Criteria for blood donor voluntary : to weigh more than 50 kg
• Criteria for severe sepsis group : Sepsis with failure of at least one organ, severe sepsis for less than 72 hours, sepsis with bacteria S. aureus, S. pneumoniae or E. coli.
• Criteria for uninfectious inflammatory syndrome group : patients operate since less than 24 hours of hip or knee surgery, Absence of systemic infection

Exclusion Criteria

• failure to participate at the study
• Patients with a aspirin treatment has continued throughout severe sepsis
• Patients with an appropriate antibiotic therapy for more than 72 hours
• Patients with a platelet transfusion in the week before inclusion or 72 hours after a surgical gesture or the occurrence of sepsis
• Patients with the platelet account is less than 30 000 per cubic millimeter the day of the sampling
• Patients with a severe sepsis who had a surgical gesture previous week the inclusion
• All clinical sequelae or biological at the selection
• pregnant woman
• Patients with a treatment by platelet aggregation has continued throughout severe sepsis

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients with severe sepsis; Blood samples will be collected at inclusion.	Other: Blood samples; Blood samples will be collected at inclusion.
patients with inflammatory syndrome without sepsis; Blood samples will be collected at inclusion.	Other: Blood samples; Blood samples will be collected at inclusion.
blood donor voluntary; Blood samples will be collected.	Other: Blood samples; Blood samples will be collected at inclusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of proportion of CD40L between the 3 groups	Comparison of proportion of CD40L in Platelet-rich plasma (PRP) between the 3 groups by proteomics technique Luminex® stimulated by Thrombin Receptor Activator Peptide (TRAP)-6).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of proportion of CD40L between patients with severe sepsis and blood donor voluntary	Comparison of proportion of CD40L in Platelet poor plasma (PPP) between patients with severe sepsis and blood donor voluntary by proteomics technique Luminex® stimulated by Thrombin Receptor Activator Peptide (TRAP)-6).	1 year
Comparison of proportion of CD40Lbetween patients with severe sepsis and patients with inflammatory syndrome without sepsis	Comparison of proportion of CD40L in Platelet-rich plasma (PRP) between patients with severe sepsis and patients with inflammatory syndrome without sepsis by proteomics technique Luminex® stimulated by Thrombin Receptor Activator Peptide (TRAP)-6).	1 year
Proportion of CD40L	Proportion of CD40L of patients with severe sepsis according to the different infection (S. aureus , S. pneumoniae, E. coli)	1 year

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: National Research Agency, France
• Investigators: Principal Investigator: Phillipe BERTHELOT, MD PhD, CHU SAINT-ETIENNE

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): July 5, 2019
• Study Completion (Actual): July 5, 2019

Study Registration Dates

• First Submitted: January 20, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 10, 2020
• Last Update Submitted That Met QC Criteria: July 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: biomarkers; inflammation; Platelet; severe sepsis; S. aureus
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Sepsis; Toxemia; Inflammation
• Other Study ID Numbers: 1608110; ID-RCB (Other Identifier: 2023-A01937-38)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No