Pediatric Immune Response to Infectious Shock

Not Applicable

Completed

• Conditions: Severe Pediatric Infectious Shock
• Interventions: Other: blood samples; Other: Collection of nosocomial infections

• Registration Number: NCT02848144
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Infectious shocks are associated with high mortality rates (20-40%). Anti-inflammatory strategies based on the postulate that mortality related to sepsis is mainly due to an overwhelming pro-inflammatory immune response have failed. Some patients surviving this initial phase can develop immune dysfunctions because the compensatory mechanisms become deleterious when they persist over time. The persistence of immunosuppression at day 3 or 5 is independently associated with more nosocomial infections and higher mortality rate. The clinical and laboratory evidence for sepsis induced immunosuppression have been recently reviewed by Hotchkiss et al. Apoptosis-induced depletion of immune effector and blood studies from septic patients showed decreased production of pro-inflammatory cytokines, decreased HLA-DR expression, increased percentage of regulatory T cells, and increased production of programmed cell death (PD)-1. Some small positive phase 2 trials of biomarker guided immune enhancing agents granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon γ (IFN γ) have been reported.

There are insufficient data showing that such an immunosuppression exists in children. Only one study performed in children with organ dysfunctions admitted to pediatric intensive care unit (PICU), showed that 34% of them developed immunosuppression. This study was performed on a heterogeneous population and immunological analyses were limited. Therefore, there is a crucial need of studies on septic patients with matched controls to provide more evidence that the same paradigm exists in children. The collaboration of laboratories with a high level of experience in this domain, and a clinical unit with a high potential of recruitment of children with severe infectious shock should allow us to perform the first prospective study specifically done in children with infectious shock.

The main hypothesis is that children with severe infectious shock developed sepsis-induced immunosuppression as shown in adults. This will be assessed by the expression of HLA-DR on monocytes' surface. We make the hypothesis that children who become immunosuppressed are more prone to develop secondary nosocomial infectious and stayed longer in PICU and in hospital.

Children aged from 1 month to 17 years, admitted to PICU at HFME Lyon-Bron are eligible if they have the criteria for severe sepsis or septic shock, defined by the "Surviving Sepsis Campaign 2012" or those of Toxic Shock Syndrome (TSS) (definitions of CDC - Center for Disease Control). An information leaflet will be issued to parents and children / adolescents and they will be informed of their right to object to the search. Are provided as part of this research:

* Immunological measures (mHLA -DR) in three stages: in the first 48 hours, between D3/5 and D7/9. The volume of collected blood will not exceed 2.4 ml / kg.

* The collection of nosocomial infections and status at D30 A control group of patients hospitalized for surgery without sepsis or toxic shock criteria will be recruited in the same hospital by ICU investigators and matched for age. Similarly controls will be given oral and written information and they will have the opportunity to deny inclusion. They will have the same exams as the first group of patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-26
• Study First Submitted: 2016-07-21
• Study First Submitted QC: 2016-07-25
• Study First Posted: 2016-07-28
• Primary Completion: 2018-08-04
• Study Completion: 2018-08-04
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-09
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Children with infectious shock	Collection of nosocomial infections	Children aged from 1 month to \<18 years. In 3 stratified groups : \<2 years, 2-8 years, and \>8 years. About one third of the patients are expected in each age-group.
Control group: healthy children	blood samples	Healthy children aged-matched to cases (same stratification group, about 20 per age group); They will be hospitalized for an elective surgery (dental, ENT, maxillofacial, urologic, hernia surgery, neurosurgery without massive hemorrhage) and without any infection.
Control group: healthy children	Collection of nosocomial infections	Healthy children aged-matched to cases (same stratification group, about 20 per age group); They will be hospitalized for an elective surgery (dental, ENT, maxillofacial, urologic, hernia surgery, neurosurgery without massive hemorrhage) and without any infection.
Children with infectious shock	blood samples	Children aged from 1 month to \<18 years. In 3 stratified groups : \<2 years, 2-8 years, and \>8 years. About one third of the patients are expected in each age-group.

Primary Outcome Measures

Name	Time	Method
proportion of patients with a mHLA-DR level significantly lower than healthy children.	in the pre-operative period	mHLA-DR is measured by flow cytometry
proportion of patients with a mHLA-DR level <30%	up to Day 9	mHLA-DR is measured by flow cytometry

Secondary Outcome Measures

Name	Time	Method
total lymphocytes	between Day 7 and day 9	From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
levels of CD4+	between Day 7 and day 9	From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
levels of T lymphocytes (Treg)	between Day 7 and day 9	From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
Number of nosocomial infections	up to Day 30
Length of vasoactive treatments	up to Day 30
Mortality	up to Day 30
levels of CD25+	between Day 7 and day 9	From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
dosage of cytokines	between Day 7 and day 9
Type of nosocomial infections	up to Day 30	bacteremia, ventilator-associated pneumonia, urinary tract infection, other sites.

Trial Locations

Locations (1)

Hospices Civils de Lyon; 🇫🇷 Lyon, France