Clinical trial NCT03979261: Predisposition to Infectious Endocarditis
Official title: Gender Study on Predisposition to Infectious Endocarditis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infective Endocarditis
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2019-06-07
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with valvulopathy or infective endocarditis requiring cardiac surgery as part of routine care.

Brief summary: To evaluate the gender-related elements, a first step will be to analyze the impact of sex ratio on different parameters such as age in endocarditis and the type of underlying valvulopathy and other associated comorbidities.

Detailed description: Numerous epidemiological studies have made it possible to highlight the impact of the genus on the occurrence and natural evolution of numerous valvulopathies. Severe valve leakage occurs more frequently in men. This association is also observed in patients with aortic bicuspid infarction where infective endocarditis (IE) is 3 times more common in men with a sex ratio of 9 to 2 to 1. Male sex is also a risk factor of AEs in the admission score used in initial patient management used to stratify the risk of AE and start probabilistic antibiotic therapy. Several hypotheses were evoked and none made it possible to understand the impact of sex on the risk of IE. The transcriptome study of IE patients revealed 2 potential biomarkers. S100A11 (S100 calcium binding protein A11) is a diagnostic marker and AQP9 (Aquaporin 9 gene) a poor prognostic factor in patients with AE. Coxiella burnetii AE is more common and more severe in humans. A study in the C57 / BL6 mouse demonstrated the role of 17 beta-estradiol in decreasing bacterial load and granuloma formation in female mice. The hypothesis formulated is that sex hormones play a role in the natural history of IS. This hypothesis was confirmed at the transcriptome level in mice and allowed to identify transcriptomic signatures according to sex; male mice with a more marked inflammatory response to C. burnetii. In order to evaluate the gender-related elements, an initial work will be to analyze the impact of sex ratio on different parameters such as age in endocarditis and the type of underlying valvulopathy and other associated comorbidities.

The second part of the project will study (i) the transcriptional profile of the native valves removed in patients with endocarditis-free valvulopathy in male and female subjects (ii) the transcriptional profile of native valves removed during endocarditis in matching sex underlying valvulopathy and microorganism. This will evaluate a possible difference in susceptibility to endocardial fixation. (iii) the transcriptional profile of PBMCs (circulating mononuclear cells) in this same patient, which will make it possible to study the transcriptional profile of the circulating genes and to evaluate the possible difference in predisposition to endocardial fixation.

Finally, the third part will focus on the histological analysis of the valves collected to study the differences between man and woman (local inflammatory reaction, cell type found).

Eligibility criteria: Inclusion Criteria:

* Patient with infectious endocarditis
* Patient with valvulopathy or infective endocarditis requiring cardiac surgery as part of routine care.
* Major patient
* Patient informed of the study and having expressed no opposition to participate in the study.
* Patient affiliated to a social security scheme.

Exclusion Criteria:

* Minor patient
* Pregnant or nursing patient.
* Patient deprived of liberty or under judicial decision.
* Major patient under tutorship or curatorship.
* Patient not agreeing to participate

Primary outcomes:
measure: Evolution of sex ratio as a function of age and underlying pathologies (comorbidities and valvulopathies)
timeFrame: 36 months
Secondary outcomes:
measure: transcriptional profile by microarray
timeFrame: 36 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Laboratoires d'immunologie et d'infectiologie
state: Cedex 5
Study officials:
affiliation: AP HM
name: Jean-Olivier ARNAUD
role: STUDY_DIRECTOR
References: