Clinical trial NCT04423523: Plasma Levels of Danger-Associated Molecular Patterns in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass
Official title: Plasma Levels of Danger-Associated Molecular Patterns (DAMPs) in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass (IMMUNOPED 2)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiac Surgical Procedure
Keywords: cardiopulmonary bypass; immunosuppression; infant
immunosuppression
infant
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 100
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients admitted to pediatric resuscitation at the Nantes University Hospital after cardiac surgery under CEC ( extra-corporal circulation) and aged less than 3 months meeting the criteria for inclusion and non-inclusion of the study will be included. We can objectify the recruitment of 80 patients in total over 3 years.

Since natural evolution (variation of rates and their kinetics) of the secretion of different DAMPs during the first months of life is unknown, the investigators added a control group to know the expression and kinetics of DAMPs outside cardiac surgery under CEC. This control group will be defined by infants under 3 months of age undergoing heavy digestive surgery and having a central venous catheter to facilitate access to blood samples (n = 20).

Brief summary: The investigators have previously reported that cardiac surgery with CPB ( cardiopulmonary bypass) in young infants induced a drastic reduction in mHLA-DR ( Human Leucocyte Antigen) expression, which represents one of innate immune mediator. Danger-Associated Molecular Patterns (DAMPs) can elicit immune response and may subsequentely induce an immune-suppressed state. The investigators hypothesize that CPB causes excessive DAMP release, leading to the development of immune suppression. Thus, DAMPs release will be assessed in patients undergoing CBP, and consequences on immune suppression will be evaluated.

Detailed description: Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 will be measured at four time points (prior to the onset of CPB, Hour 6 postoperative, day 1 and day 3 after surgery). HLA-DR gene expression will be determined before surgery and at day 3 postoperative. The direct effect of DAMPs release and immune suppression will be assessed by in vitro experiments.

Eligibility criteria: Inclusion Criteria:

* Patient admitted to pediatric intensive care at Nantes University Hospital after cardiac surgery with bypass graft
* Age ≤ 3 months corrected age. Control group: patients less than 3 months old following cardiac surgery without CEC or digestive surgery with a central venous catheter.

Exclusion Criteria:

* Futility of care with cessation of blood tests as part of a limitation of active therapies;
* Absence of parents for information
* Refusal of parents after information (Lack of parental consent)
* Blood volume collected for medical purposes incompatible with the needs of the research

Primary outcomes:
measure: Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.
timeFrame: prior to the onset of CPB, 6 hours, day 1 and day 3 after surgery
Secondary outcomes:
measure: Effect of DAMPs on immune function:In vitro change of HLA-DR expression.
timeFrame: 6 hours after surgery
measure: Effect of DAMPs on immune function:Secretion of IL-10 ( Interleukine 10).
timeFrame: 6 hours after surgery
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes University Hospital
Study officials:
affiliation: Nantes University Hospital
name: Alexis Chenouard
role: PRINCIPAL_INVESTIGATOR
References: