Condition or disease | Intervention/treatment |
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Infective Endocarditis | Diagnostic Test: evolution of sex ratio according to age |
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 |
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 |
Group/Cohort | Intervention/treatment |
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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.
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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.
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Sampling Method: | Probability Sample |
Inclusion Criteria:
Exclusion Criteria:
Contact: Didier RAOULT, IP | 04 13 73 20 5 | didier.raoult@ap-hm.fr |
France | |
Laboratoires d'immunologie et d'infectiologie | |
Marseille, Cedex 5, France, 13354 | |
Contact: Didier RAOULT didier.raoult@ap-hm.fr |
Study Director: | Jean-Olivier ARNAUD | AP HM |
Tracking Information | |||||
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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 |
Evolution of sex ratio as a function of age and underlying pathologies (comorbidities and valvulopathies) [ Time Frame: 36 months ] | ||||
Original Primary Outcome Measures |
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.
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Change History | |||||
Current Secondary Outcome Measures |
transcriptional profile by microarray [ Time Frame: 36 months ] rate of indigenous valves removed in patients with valvulopathy without endocarditis by gender
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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). |
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Study Type | Observational | ||||
Study Design | Observational Model: Cohort Time Perspective: Prospective |
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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.
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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
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Not yet recruiting | ||||
Estimated Enrollment |
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:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers | Not Provided | ||||
Contacts |
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Listed Location Countries | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT03979261 | ||||
Other Study ID Numbers | 2018-58 2018-A02503-52 ( Registry Identifier: APHM ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement | Not Provided | ||||
Responsible Party | Assistance Publique Hopitaux De Marseille | ||||
Study Sponsor | Assistance Publique Hopitaux De Marseille | ||||
Collaborators | Not Provided | ||||
Investigators |
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PRS Account | Assistance Publique Hopitaux De Marseille | ||||
Verification Date | June 2019 |