Metabolic Profiling Among Patients Suspected of Infective Endocarditis - PPSIE Comparing Metabolomes of Bloodstream Infections Versus Infective Endocarditis (PPSIE)
Most cases of Infective endocarditis (IE) are caused by Gram-positive bacteria, primarily Staphylococcus aureus, oral or intestinal streptococci, and enterococci (especially Enterococcus faecalis). Blood cultures for these bacteria may indicate simple bacteremia (without cardiac involvement) or endocarditis. The proportion of patients with IE among those presenting with positive blood cultures varies depending on the pathogen (approximately 10% for S. aureus, 5 to 50% for oral streptococci, depending on the species, and 15% for E. faecalis).
The PPSIE study aims to identify a specific biological signature of infective endocarditis that would allow identification of valvular involvement in patients with positive blood cultures.
Patients will be selected based on a blood culture positive for one of the following organisms: S. aureus, S. mutans, S. gordonii, S. sanguinis, S. parasanguinis, S. gallolyticus, S. mitis/oralis, E. faecalis, as well as based on the likelihood of endocarditis determined by a clinical score specific to the causative pathogen (VIRSTA, HANDOC, or DENOVA) A blood sample will be collected 1 day, 5 days, and 3 months after enrollment. Patients will be classified into the groups "bacteremia without cardiac involvement (BasAC)," "definite infectious endocarditis (confirmed IE)," or "possible infectious endocarditis" according to the Duke classification modified by the ISCVID in 2023; uncertain cases will be assessed by an adjudication committee. Untergeted metabolomic analysis will be performed on these blood samples in order to find a metabolic signature able to discriminate patients with endocarditis from those without cardiac involvement. The prediction model will be built using a total of 80 patients, comprising 40 "confirmed IE" patients and 40 "IE excluded" (BasAC) patients.
The model will then be validated using a randomly selected sample from the "possible IE" group, according to the Duke classification modified by the ISCVID in 2023.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Aurélie Hautefort
- Número de telefone: +33 02 41 35 36 37
- E-mail: DRCI-Promotion-Interne@chu-angers.fr
Estude backup de contato
- Nome: Vincent Dubée, Pr
- Número de telefone: +33 02 41 35 36 37
- E-mail: Vincent.Dubee@chu-angers.fr
Locais de estudo
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Le Mans, França, 72000
- Centre Hospitalier Le Mans
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Contato:
- Lucia Perez
- Número de telefone: +33 0243434352
- E-mail: lperez@ch-lemans.fr
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Nantes, França, 44093
- CHU de Nantes
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Contato:
- Benjamin Gaborit
- Número de telefone: +33 0244768292
- E-mail: benjamin.gaborit@chu-nantes.fr
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Tours, França, 37044
- CHU de Tours
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Contato:
- Adrien Lemaignen
- Número de telefone: +33 0218370644
- E-mail: a.lemaignen@univ-tours.fr
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria :
- Adult patient
- Blood culture positive for one of the following organisms: S. aureus, S. mutans, S. gordonii, S. sanguinis, S. parasanguinis, S. gallolyticus, S. mitis/oralis, E. faecalis
- Patient enrolled in or covered by a social security program
- Patient who has signed an informed consent form
Exclusion Criteria:
- Expected time between the start of antibiotic treatment and the collection of the blood sample for the study (the morning after the consent form is signed) exceeding 5 days
- Polymicrobial blood culture, defined as the presence of more than one microbial species in the same blood culture bottle or in several different bottles during the same infectious episode, with the exception of organisms whose presence indicates bottle contamination, such as coagulase-negative staphylococci, Bacillus sp., Cutibacterium sp., Micrococcus sp., Corynebacterium sp.
- Low risk of endocarditis, estimated by a clinical score:
- VIRSTA score < 3 for S. aureus bacteremias
- HANDOC score < 3 for streptococcal bacteremias
- DENOVA score < 3 for E. faecalis bacteremias
- Patients whose medical condition raises concerns about death within 3 months
- Pregnant, breastfeeding, or laboring women
- Individuals deprived of liberty by judicial or administrative order
- Individuals receiving involuntary psychiatric care
- Individuals subject to a legal protective measure
- Individuals unable to give informed consent
- Poor understanding of the French language
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Diagnóstico
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Patients included in the study
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Blood sample |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Metabolomic signature
Prazo: Day 1 and Day 5 after enrollement
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The existence of a metabolic signature will be confirmed by the presence of a latent variable predictive of cardiac involvement in the study population. This variable will be selected after comparing the metabolic profiles between the 'confirmed EI' group and the Bacteremia Without Cardiac Involvement (BaSAC) group for each time point considered (Day 1 and Day 5). To avoid overfitting, the predictive ability of the multivariate model (orthogonal partial least squares in the context of discriminant analysis, or OPLS-DA) will be evaluated using "standard" criteria as implemented in the SIMCA software, with a low prediction error rate (Q2Ycum ≥ 0.5) and performance significantly superior to that of the random model (P-value (CV-ANOVA) ≤ 0.05, Q2Ycum from the permutation test < 0). |
Day 1 and Day 5 after enrollement
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Identify potential biomarkers (BM) that can distinguish patients with BaSAC from those with EI.
Prazo: Day 1 and Day 5 after enrollement
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Metabolites, as well as the ratio(s) or sum(s) of metabolites, with a median value that is significantly different between the two groups (BaSAC and EI) will be considered potential BMs for EI, after adjusting for potential sources of confounding (center, germ, etc.) and after correcting for Type I error inflation. The potential BM(s) may or may not be part of the metabolomic signature (see Primary Objective), as applicable. |
Day 1 and Day 5 after enrollement
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Describe changes in the metabolic signature in patients with endocarditis 5 days and 3 months after enrollment and correlate these changes with the diagnosis of IE.
Prazo: Day 1, Day 5, and Month 3 after enrollment
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Proportion of patients in the endocarditis group in whom normalization of the metabolic signature was observed during follow-up (Day 5). Comparison of metabolite concentrations in the same patient across samples collected on Day 1, Day 5, and Month 3 to identify statistically significant changes in the levels of metabolites of interest. Normalization defined as a correlation with the normalization of clinical, laboratory, and microbiological parameters. |
Day 1, Day 5, and Month 3 after enrollment
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Diagnostic performance of the identified biomarker(s) in a subset of patients with "possible" endocarditis according to the Duke classification revised by the ISCVID in 2023.
Prazo: Day 1, Day 5, and Month 3 after enrollment
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Calculation of sensitivity, specificity, positive predictive value, and negative predictive value of the identified biomarker(s) for the diagnosis of infective endocarditis at each time point considered (Day 1, Day 5, and Month 3). A panel of experts will serve as the gold standard for the diagnosis of infective endocarditis. |
Day 1, Day 5, and Month 3 after enrollment
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Conduct a sensitivity analysis on the correct classification of patients as "definite IE" according to the Duke classification revised by the ISCVID in 2023 by comparing it with the Duke and Li classification.
Prazo: Month 3 after enrollment
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calculation of the proportion of discordant cases between "definite IE" cases according to the Duke classification revised by the ISCVID in 2023 and the Duke and Li classification. |
Month 3 after enrollment
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 49RC24_0250
- 2026-A00993-48 (Outro identificador: ANSM)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Data will be shared upon reasonable request. Only de-identified data will be shared. Any data collected during the study may be shared. The protocol will be shared initially. Other documents may be shared at a later date upon request (e.g., the CRF to allow a collaborator to select the data they wish to access). The recipients of the data will be researchers. The data will be available for any purpose deemed relevant by the study investigator, based on a protocol provided by the requester, after verification of the obtaining of regulatory approvals, including the favorable opinion of an ethics committee.
Prazo de Compartilhamento de IPD
The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement.
Critérios de acesso de compartilhamento IPD
The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
Informações sobre medicamentos e dispositivos, documentos de estudo
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