PedIMOD: Pediatric Immune Response to Multi-Organ Dysfunction

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Recruiting

CT.gov ID

NCT04438460

Collaborator

(none)

210

Enrollment

Locations

Arms

Anticipated Duration (Months)

105

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Organ Dysfunction Syndrome	Biological: Blood test	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

210 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Pediatric Immune Response to Multi-Organ Dysfunction

Actual Study Start Date :

Jul 29, 2020

Anticipated Primary Completion Date :

Sep 29, 2023

Anticipated Study Completion Date :

Sep 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patient group 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 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.
Other: Control group 60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study	Biological: Blood test 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.

Arm

Intervention/Treatment

Experimental: Patient group

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

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.

Other: Control group

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

Biological: Blood test

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.

Outcome Measures

Primary Outcome Measures

mHLA-DR measurement [Day 3]
The proportion of children with mHLA-DR < 8000 sites / cells on Day 3 - Day 5 will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months. The diagnosis of secondary acquired infection will be made by an independent committee.

Secondary Outcome Measures

blood counts : Characterization of alterations in the myeloid lineage [Day 1]
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
mHLA-DR expression : Characterization of alterations in the myeloid lineage [Day 1]
mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months
transcriptome : Characterization of alterations in the myeloid lineage [Day 1]
Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
plasma cytokines : Characterization of alterations in the myeloid lineage [Day 1]
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
blood counts : Characterization of alterations in the myeloid lineage [Day 3]
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months
mHLA-DR expression : Characterization of alterations in the myeloid lineage [Day 3]
mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
transcriptome : Characterization of alterations in the myeloid lineage [Day 3]
Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
plasma cytokines : Characterization of alterations in the myeloid lineage [Day 3]
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
blood counts : Characterization of alterations in the myeloid lineage [Day 60]
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
mHLA-DR expression : Characterization of alterations in the myeloid lineage [Day 60]
mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
transcriptome : Characterization of alterations in the myeloid lineage [Day 60]
Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
plasma cytokines : Characterization of alterations in the myeloid lineage [Day 60]
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Secondary acquired infection [Day 60]
The incidence of secondary acquired infections occurring within 2 months will be compared between the groups "immunosuppression" and "no immunosuppression".
mHLA-DR measurement [Day 60]
Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient Group:

1 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:

1 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

Exclusion Criteria:

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)

Control Group:

Weight < 5 kg
Known immunosuppression
Prolonged corticotherapy
Chronic inflammatory disease
Malignant pathology with ongoing treatment
Ongoing infection
Organ failure
Hepatic cirrhosis
PCR SARS-CoV-2 positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)