Multiple Organ Dysfunction SyndromePedIMODNCT04438460
Pediatric Immune Response to Multi-Organ Dysfunction
A study testing Blood test in people with Multiple Organ Dysfunction Syndrome, run by Hospices Civils de Lyon at 2 sites in France.
Trial 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%). Read more about this study
- Who is it for?
- Ages 1 month to 12 years
- Conditions the study is for
- Multiple Organ Dysfunction Syndrome
- What is being tested?
- Blood test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 2 sitesFrance
- Study dates
- 29 Jul 2020to 16 Apr 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
Show all 10Show fewer
- 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
Who cannot join
- Patient Group:
- Weight < 5 kg
- Known immunosuppression
- Prolonged corticotherapy
- Chronic inflammatory disease
- Malignant pathology with ongoing treatment
Show all 20Show fewer
- 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
- Ongoing infection
- Organ failure
- Hepatic cirrhosis
- PCR SARS-CoV-2 positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)
- Pediatric inflammatory multisystem syndrome (PIMS)
Trial locations and contacts
2 sites in 1 country.
France2 sites
Hôpital Femme Mère Enfant
Bron, 69500
Hopital Mère Enfant
Nantes, 44093
About this study
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.
Read more
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
- Being tested
- Blood test
- Keywords
- Multiple organ dysfunction, Immunosuppression, mHLA-DR, Pediatrics, Secondary infection
- Medical subject headings
- Multiple Organ Failure, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood testBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: Blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 60
Secondary outcomes (23)
blood counts : Characterization of alterations in the myeloid lineage
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Measured: Day 1
mHLA-DR expression : Characterization of alterations in the myeloid lineage
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
Measured: Day 1
transcriptome : Characterization of alterations in the myeloid lineage
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.
Measured: Day 1
plasma cytokines : Characterization of alterations in the myeloid lineage
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Measured: Day 1
blood counts : Characterization of alterations in the myeloid lineage
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months
Measured: Day 3
mHLA-DR expression : Characterization of alterations in the myeloid lineage
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.
Measured: Day 3
transcriptome : Characterization of alterations in the myeloid lineage
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.
Measured: Day 3
plasma cytokines : Characterization of alterations in the myeloid lineage
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Measured: Day 3
blood counts : Characterization of alterations in the myeloid lineage
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Measured: Day 60
mHLA-DR expression : Characterization of alterations in the myeloid lineage
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.
Measured: Day 60
transcriptome : Characterization of alterations in the myeloid lineage
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.
Measured: Day 60
plasma cytokines : Characterization of alterations in the myeloid lineage
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Measured: Day 60
mHLA-DR measurement
Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.
Measured: Day 60
Myeloid Derived Suppressor Cells (MDSC) measurement
Characterization of MDSC will be measured and compared between patient and control
Measured: Day 1
Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte
Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte. It will be compared between patient and control.
Measured: Day 1
MDSC measurement
Characterization of MDSC will be measured
Measured: Day 3
Intra-cellular production of TNFα by the monocyte
Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte.
Measured: Day 3
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.
Measured: Day 1
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.
Measured: Day 1
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized
Measured: Day 3
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized
Measured: Day 3
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized
Measured: Day 60
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized
Measured: Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start29 Jul 2020
- Primary completion16 Apr 2024
- Study completion16 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Organ Dysfunction SyndromeStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04438460
- Sponsor's protocol ID
- 69HCL20_0068
- Other IDs
- 2020-A00343-36
- Acronym
- PedIMOD
- Status last verified
- May 2024
- First submitted
- 28 May 2020
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric Immune Response to Multi-Organ Dysfunction
- ClinicalTrials.gov ID
- NCT04438460
- Acronym / sponsor ID
- PedIMOD / 69HCL20_0068
- Conditions
- Multiple Organ Dysfunction Syndrome
- Keywords
- Multiple organ dysfunction, Immunosuppression, mHLA-DR, Pediatrics, Secondary infection
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 29 Jul 2020 (actual)
- Primary completion
- 16 Apr 2024 (actual)
- Study completion
- 16 Apr 2024 (actual)
- First posted
- 18 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient group | Experimental | Biological: Blood test150 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 |
| Control group | Other | Biological: Blood test60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study |
Who may qualify
- Ages
- 1 month to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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
- 1 month < Age < 12 years
Key exclusion criteria (20 listed)
- Weight < 5 kg
- Known immunosuppression
- Prolonged corticotherapy
- Chronic inflammatory disease
- Malignant pathology with ongoing treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood testFor 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. | Biological | Control group, Patient group |
Primary outcome
Secondary acquired infection (SAI)
Time frame: Day 60
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.
23 secondary outcomes
blood counts : Characterization of alterations in the myeloid lineage
Time frame: Day 1
mHLA-DR expression : Characterization of alterations in the myeloid lineage
Time frame: Day 1
transcriptome : Characterization of alterations in the myeloid lineage
Time frame: Day 1
plasma cytokines : Characterization of alterations in the myeloid lineage
Time frame: Day 1
blood counts : Characterization of alterations in the myeloid lineage
Time frame: Day 3
mHLA-DR expression : Characterization of alterations in the myeloid lineage
Time frame: Day 3
transcriptome : Characterization of alterations in the myeloid lineage
Time frame: Day 3
plasma cytokines : Characterization of alterations in the myeloid lineage
Time frame: Day 3
blood counts : Characterization of alterations in the myeloid lineage
Time frame: Day 60
mHLA-DR expression : Characterization of alterations in the myeloid lineage
Time frame: Day 60
transcriptome : Characterization of alterations in the myeloid lineage
Time frame: Day 60
plasma cytokines : Characterization of alterations in the myeloid lineage
Time frame: Day 60
mHLA-DR measurement
Time frame: Day 60
Myeloid Derived Suppressor Cells (MDSC) measurement
Time frame: Day 1
Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte
Time frame: Day 1
MDSC measurement
Time frame: Day 3
Intra-cellular production of TNFα by the monocyte
Time frame: Day 3
Monocytic and dendritic subpopulations measurement
Time frame: Day 1
Gamma-delta T lymphocytes measurement
Time frame: Day 1
Monocytic and dendritic subpopulations measurement
Time frame: Day 3
Gamma-delta T lymphocytes measurement
Time frame: Day 3
Monocytic and dendritic subpopulations measurement
Time frame: Day 60
Gamma-delta T lymphocytes measurement
Time frame: Day 60
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood test in people with Multiple Organ Dysfunction Syndrome, run by Hospices Civils de Lyon at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Secondary acquired infection (SAI) (time frame: Day 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.