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出境医 / 临床实验 / Predisposition to Infectious Endocarditis

Predisposition to Infectious Endocarditis

Study Description
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.

Condition or disease Intervention/treatment
Infective Endocarditis Diagnostic Test: evolution of sex ratio according to age

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).

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 450 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Gender Study on Predisposition to Infectious Endocarditis
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2022
Arms and Interventions
Group/Cohort Intervention/treatment
sex ratio evaluation
Valvular surgery is performed in 30-40% of cases. The Cardiology and Cardiac Surgery De la Timone services 1000 patients as part of their valvulopathy and 450 benefit from cardiac surgery. On the other hand, transcriptomic analysis by microarray will only be done on 40 patients because the analysis costs 150 € / patients.
Diagnostic Test: evolution of sex ratio according to age
Histological study of the collected valves to study the differences according to the sex of the inflammatory reaction and the cellular type found.

Outcome Measures
Primary Outcome Measures :
  1. Evolution of sex ratio as a function of age and underlying pathologies (comorbidities and valvulopathies) [ Time Frame: 36 months ]

Secondary Outcome Measures :
  1. transcriptional profile by microarray [ Time Frame: 36 months ]
    rate of indigenous valves removed in patients with valvulopathy without endocarditis by gender


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Patient with valvulopathy or infective endocarditis requiring cardiac surgery as part of routine care.
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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Didier RAOULT, IP 04 13 73 20 5 didier.raoult@ap-hm.fr

Locations
Layout table for location information
France
Laboratoires d'immunologie et d'infectiologie
Marseille, Cedex 5, France, 13354
Contact: Didier RAOULT       didier.raoult@ap-hm.fr   
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
Layout table for investigator information
Study Director: Jean-Olivier ARNAUD AP HM
Tracking Information
First Submitted Date June 6, 2019
First Posted Date June 7, 2019
Last Update Posted Date June 14, 2019
Estimated Study Start Date July 1, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 12, 2019)
Evolution of sex ratio as a function of age and underlying pathologies (comorbidities and valvulopathies) [ Time Frame: 36 months ]
Original Primary Outcome Measures
 (submitted: June 6, 2019)
transcriptional profile by microarray [ Time Frame: 1 day ]
Native valves removed in patients with valvulopathy with Native valves infected by matching sex, underlying valvulopathy and the causative microorganism PBMC (circulating mononuclear cells) in infected patients and in healthy patients.
Change History
Current Secondary Outcome Measures
 (submitted: June 12, 2019)
transcriptional profile by microarray [ Time Frame: 36 months ]
rate of indigenous valves removed in patients with valvulopathy without endocarditis by gender
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Predisposition to Infectious Endocarditis
Official Title Gender Study on Predisposition to Infectious Endocarditis
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).

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population Patient with valvulopathy or infective endocarditis requiring cardiac surgery as part of routine care.
Condition Infective Endocarditis
Intervention Diagnostic Test: evolution of sex ratio according to age
Histological study of the collected valves to study the differences according to the sex of the inflammatory reaction and the cellular type found.
Study Groups/Cohorts sex ratio evaluation
Valvular surgery is performed in 30-40% of cases. The Cardiology and Cardiac Surgery De la Timone services 1000 patients as part of their valvulopathy and 450 benefit from cardiac surgery. On the other hand, transcriptomic analysis by microarray will only be done on 40 patients because the analysis costs 150 € / patients.
Intervention: Diagnostic Test: evolution of sex ratio according to age
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: June 6, 2019)
450
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 1, 2022
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Didier RAOULT, IP 04 13 73 20 5 didier.raoult@ap-hm.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT03979261
Other Study ID Numbers 2018-58
2018-A02503-52 ( Registry Identifier: APHM )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Assistance Publique Hopitaux De Marseille
Study Sponsor Assistance Publique Hopitaux De Marseille
Collaborators Not Provided
Investigators
Study Director: Jean-Olivier ARNAUD AP HM
PRS Account Assistance Publique Hopitaux De Marseille
Verification Date June 2019

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