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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Aurélie Hautefort
- Numéro de téléphone: +33 02 41 35 36 37
- E-mail: DRCI-Promotion-Interne@chu-angers.fr
Sauvegarde des contacts de l'étude
- Nom: Vincent Dubée, Pr
- Numéro de téléphone: +33 02 41 35 36 37
- E-mail: Vincent.Dubee@chu-angers.fr
Lieux d'étude
-
-
-
Le Mans, France, 72000
- Centre Hospitalier Le Mans
-
Contact:
- Lucia Perez
- Numéro de téléphone: +33 0243434352
- E-mail: lperez@ch-lemans.fr
-
Nantes, France, 44093
- CHU de Nantes
-
Contact:
- Benjamin Gaborit
- Numéro de téléphone: +33 0244768292
- E-mail: benjamin.gaborit@chu-nantes.fr
-
Tours, France, 37044
- CHU de Tours
-
Contact:
- Adrien Lemaignen
- Numéro de téléphone: +33 0218370644
- E-mail: a.lemaignen@univ-tours.fr
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Diagnostique
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Patients included in the study
|
Blood sample |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Metabolomic signature
Délai: Day 1 and Day 5 after enrollement
|
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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Identify potential biomarkers (BM) that can distinguish patients with BaSAC from those with EI.
Délai: Day 1 and Day 5 after enrollement
|
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
|
|
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.
Délai: Day 1, Day 5, and Month 3 after enrollment
|
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
|
|
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.
Délai: Day 1, Day 5, and Month 3 after enrollment
|
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
|
|
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.
Délai: Month 3 after enrollment
|
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
|
Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 49RC24_0250
- 2026-A00993-48 (Autre identifiant: ANSM)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime 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.
Délai de partage IPD
The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement.
Critères d'accès au partage IPD
The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .