Pediatric Immune Response to Multi-Organ Dysfunction

NCT04438460 | Completed

• 2 other identifiers: 69HCL20_00682020-A00343-36
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 2

Brief Summary

Multiple organ dysfunction (MOD) is defined by the association of at least two failures of vital organs, with various etiologies (septic shock, polytrauma, acute respiratory distress syndrome, etc.). Associated mortality remains high in children (between 20 and 50%). In septic shock, one of the main causes of MOD, induced immunosuppression can occur, with immune alterations affecting all cells of immunity. This induced immunosuppression is associated with an additional risk of secondary acquired infections and death in adults. Among all the cells and all the markers studied, the expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the surface of the monocyte (mHLA-DR, expressed in number of sites per cell) appeared as one of the best biomarkers of this induced immunosuppression. Decreased expression of monocyte Human Leukocyte Antigen - DR isotype (mHLA-DR) in adults is linked to an increased risk of developing secondary infection and death. These results were confirmed by team in the context of pediatric septic shock, with an attack of innate immunity in the foreground. Persistent lowering of mHLA-DR for more than 3 days after onset of shock was associated with the occurrence of secondary acquired infections: 50% of children had mHLA-DR of less than 8000 sites / cells on D3, of which 60 % developed secondary infection within 30 days. No child with mHLA-DR greater than 8000 sites / cells had secondary infection. Such immune alterations appear to be non-specific for septic shock, as they have also been described after multiple trauma or severe respiratory infections. The hypothesize is that multi-systemic aggression leading to multi-visceral failure syndrome could also lead to significant immunosuppression, regardless of the etiology of this MOD. At present, the proportion of persistent immunosuppression induced by MOD, all etiologies combined, is poorly documented in pediatrics. Estimating this proportion in a large pediatric cohort, while exploring as fully as possible the associated immune alterations and acquired secondary infections, would improve the pathophysiological understanding and pediatric specificities of this phenomenon.

Conditions

Multiple Organ Dysfunction Syndrome

Keywords

Multiple organ dysfunction; Immunosuppression; mHLA-DR; Pediatrics; Secondary infection

Outcome Measures

Primary Outcomes (1)

• Secondary acquired infection (SAI)

  This criterion will be related to the duration of follow-up and expressed as an incidence of SAI occurrence.This incidence will be calculated in the two groups "Presence of immunosuppression" and "Absence of immunosuppression", defined from the value of mHLA-DR at D3-D5: "Presence of immunosuppression" if mHLA-DR \< 8000 sites/cells and "Absence of immunosuppression" if mHLA-DR ≥ 8000 sites/cells. The diagnosis of secondary acquired infection will be made by an independent committee.

  Day 60

Secondary Outcomes (23)

• blood counts : Characterization of alterations in the myeloid lineage

  Day 1

• mHLA-DR expression : Characterization of alterations in the myeloid lineage

  Day 1

• transcriptome : Characterization of alterations in the myeloid lineage

  Day 1

• plasma cytokines : Characterization of alterations in the myeloid lineage

  Day 1

• blood counts : Characterization of alterations in the myeloid lineage

  Day 3

Study Arms (2)

Patient group

EXPERIMENTAL

150 children aged 1 month to 12 years with multi-visceral failure syndrome within 48 hours of hospitalization in pediatric resuscitation will be included in this study

Biological: Blood test

Control group

OTHER

60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study

Biological: Blood test

Interventions

Blood test BIOLOGICAL

For patient group, blood tests will be performed at day 1-2, day 3-5 and day 60. For control group, blood test will be performed the day of elective surgery.

Control group; Patient group

Eligibility Criteria

• Age: 1 Month - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patient Group:
• month \< Age \< 12 years
• Multiple organ dysfunction within 48 hours following intensive care unit admission
• Beneficiary of a social security scheme.
• Consent signed by at least one parent / holder of parental authority
• Control Group:
• month \< Age \< 12 years
• Hospitalized for simple elective surgery
• Beneficiary of a social security scheme.
• Consent signed by at least one parent / holder of parental authority

You may not qualify if:

• Patient Group:
• Weight \< 5 kg
• Known immunosuppression
• Prolonged corticotherapy
• Chronic inflammatory disease
• Malignant pathology with ongoing treatment
• Hepatic cirrhosis
• Polymerase Chain Reaction (PCR) Severe acute respiratory syndrome coronavirus (SARS-CoV-2) positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)
• Pediatric inflammatory multisystem syndrome (PIMS)
• Control Group:
• Weight \< 5 kg
• Known immunosuppression
• Prolonged corticotherapy
• Chronic inflammatory disease
• Malignant pathology with ongoing treatment

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Hôpital Femme Mère Enfant

Bron, 69500, France

Location

Hopital Mère Enfant

Nantes, 44093, France

Location

MeSH Terms

Conditions

Multiple Organ Failure; Coinfection

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 18, 2020
• Study Start: July 29, 2020
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Locations

FR (2)