Plasma Levels of Danger-Associated Molecular Patterns in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass (IMMUNOPED2)

Plasma Levels of Danger-Associated Molecular Patterns (DAMPs) in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass (IMMUNOPED 2)

The investigators have previously reported that cardiac surgery with cardiopulmonary bypass (CPB) 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 subsequently induce an immune-suppressed state. We hypothesize that analyzing the proteomic and the whole blood transcriptomic response after cardiac surgery would provide new insights into the pathophysiological mechanisms of CPB-related inflammatory response.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgical Procedure
• Intervention / Treatment: Diagnostic test: Blood drop sampling

Detailed Description

Plasma levels of heat shock protein and inflammatory-related proteins will be measured at four time points (prior to the onset of surgery, Hour 6 postoperative, day 1 and day 3 after surgery). Whole blood transcriptomic analysis will be performed before and after surgery. The immune suppression induced by CPB will be assessed by in vitro experiments.

• Study Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Nantes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No

• 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).

Description

Inclusion Criteria:

• Patient admitted to pediatric intensive care at Nantes University Hospital after cardiac surgery
• Age ≤ 3 months corrected age.
• Control group: patients less than 3 months old following cardiac surgery without CPB 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study population; The study population must correspond to the research inclusion criteria: Patient admitted to pediatric intensive care at Nantes University Hospital after cardiac surgery on bypass grafts	Diagnostic test: Blood drop sampling; For each patient included, 1 additional EDTA blood tube (2 ml) will be collected for research purposes at different times (4 visits), and 1 PAXgene-type tube adapted for pediatric collection of only 500 μl (2 visits).
Control group; Infants under 3 months of age undergoing heavy digestive surgery and having a central venous catheter to facilitate access to blood samples.	Diagnostic test: Blood drop sampling; For each patient included, 1 additional EDTA blood tube (2 ml) will be collected for research purposes at different times (4 visits), and 1 PAXgene-type tube adapted for pediatric collection of only 500 μl (2 visits).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of inflammation-related proteins, including some DAMPs, heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9, IL-33 before and after surgery.	Change of plasma levels of inflammation-related proteins before and after surgery.	prior to the onset of CPB, 6 hours, day 1 and day 3 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole blood transcriptome before and after surgery.	Whole blood transcriptomic analysis before and after surgery.	Prior to the onset of surgery and 6 hours after surgery
Characterization of CPB-immune dysfunction in vitro	In vitro experiments with immune cells phenotyping, in vitro-stimulation and intracellular cytokine staining.	Prior to the onset of surgery and 6 hours after surgery

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Alexis Chenouard, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Actual): June 27, 2023
• Study Completion (Actual): December 2, 2025

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: June 7, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: immunosuppression; infant; cardiopulmonary bypass; immunosuppression; infant
• Other Study ID Numbers: RC19_0402

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No