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Pediatric Immune Response to Infectious Shock (PedIRIS)

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ClinicalTrials.gov Identifier: NCT02848144
Recruitment Status : Completed
First Posted : July 28, 2016
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Severe Pediatric Infectious Shock Other: blood samples Other: Collection of nosocomial infections Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pediatric Immune Response to Infectious Shock
Actual Study Start Date : September 26, 2014
Actual Primary Completion Date : August 4, 2018
Actual Study Completion Date : August 4, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Children with infectious shock
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.
Other: blood samples
Other: Collection of nosocomial infections
Control group: healthy children
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.
Other: blood samples
Other: Collection of nosocomial infections



Primary Outcome Measures :
  1. proportion of patients with a mHLA-DR level <30% [ Time Frame: up to Day 9 ]
    mHLA-DR is measured by flow cytometry

  2. proportion of patients with a mHLA-DR level significantly lower than healthy children. [ Time Frame: in the pre-operative period ]
    mHLA-DR is measured by flow cytometry


Secondary Outcome Measures :
  1. total lymphocytes [ Time Frame: Day 1 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  2. total lymphocytes [ Time Frame: between Day 3 and day 5 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  3. total lymphocytes [ Time Frame: 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

  4. levels of CD4+ [ Time Frame: Day 1 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  5. levels of CD4+ [ Time Frame: between Day 3 and day 5 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  6. levels of CD4+ [ Time Frame: 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

  7. levels of CD25+ [ Time Frame: day 1 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  8. levels of CD25+ [ Time Frame: between Day 3 and day 5 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  9. levels of CD25+ [ Time Frame: 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

  10. levels of T lymphocytes (Treg) [ Time Frame: Day 1 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  11. levels of T lymphocytes (Treg) [ Time Frame: between Day 3 and day 5 ]
    From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies

  12. levels of T lymphocytes (Treg) [ Time Frame: 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

  13. dosage of cytokines [ Time Frame: Day 1 ]
  14. dosage of cytokines [ Time Frame: between Day 3 and day 5 ]
  15. dosage of cytokines [ Time Frame: between Day 7 and day 9 ]
  16. Number of nosocomial infections [ Time Frame: up to Day 30 ]
  17. Type of nosocomial infections [ Time Frame: up to Day 30 ]
    bacteremia, ventilator-associated pneumonia, urinary tract infection, other sites.

  18. Mortality [ Time Frame: up to Day 30 ]
  19. Length of vasoactive treatments [ Time Frame: up to Day 30 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria Infectious shock group:

  • Children aged from 1 month to <18 years
  • Diagnosis of severe infectious shock at PICU or within the first 24 hours following PICU admission: severe sepsis or septic shock, defined by Surviving Sepsis Campaign 2012, or Toxic Shock Syndrome, defined by CDC criteria.

Inclusion Criteria Control group:

  • Healthy children aged matched to cases
  • Hospitalized for an elective surgery (dental, ENT, maxillofacial, urologic, hernia surgery, neurosurgery without massive hemorrhage)
  • Without any criteria of infection.

Exclusion Criteria (both groups):

  • Chronic inflammatory disease;
  • Immunodeficiency;
  • Long-term corticosteroids;
  • Ongoing immunosuppressive treatment;
  • Transplanted patients;
  • Tumors, hematological diseases;
  • No health insurance coverage;
  • Refusal to participate (from parents and/or patient) or inability to understand information.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02848144


Locations
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France
Hospices Civils de Lyon
Lyon, France
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Etienne JAVOUHEY Hospices Civils de Lyon

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02848144     History of Changes
Other Study ID Numbers: 69HCL16_0478
First Posted: July 28, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Hospices Civils de Lyon:
Immunoparalysis
immune response
sepsis
toxic shock syndrome

Additional relevant MeSH terms:
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Shock
Communicable Diseases
Infection
Pathologic Processes