Infective Endocarditis (IE)PPSIENCT07917325
Metabolic Profiling Among Patients Suspected of Infective Endocarditis - PPSIE Comparing Metabolomes of Bloodstream Infections Versus Infective Endocarditis
A study testing Blood sample in people with Infective Endocarditis (IE), run by University Hospital, Angers at 3 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infective Endocarditis (IE)
- What is being tested?
- Blood sample
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 3 sitesFrance
- Study dates
- Nov 2026to Nov 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites
Centre Hospitalier Le Mans
Le Mans, 72000
Lucia Perez, 0243434352 ext. +33, lperez@ch-lemans.fr
CHU de Nantes
Nantes, 44093
Benjamin Gaborit, 0244768292 ext. +33, benjamin.gaborit@chu-nantes.fr
CHU de Tours
Tours, 37044
Adrien Lemaignen, 0218370644 ext. +33, a.lemaignen@univ-tours.fr
About this study
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.
Read more
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.
- Conditions
- Infective Endocarditis (IE)
- Being tested
- Blood sample
- Keywords
- Infective endocarditis (IE), bacteriema, metabolomic profile
- Medical subject headings
- Endocarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleProcedure or surgery
Blood sample
| Study group | Role | What they receive |
|---|---|---|
| Patients included in the study | Experimental | Not described Receives: Procedure: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolomic signature
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).
Measured: Day 1 and Day 5 after enrollement
Secondary outcomes (4)
Identify potential biomarkers (BM) that can distinguish patients with BaSAC from those with EI.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: Month 3 after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infective Endocarditis (IE)Studies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07917325
- Sponsor's protocol ID
- 49RC24_0250
- Other IDs
- 2026-A00993-48
- Acronym
- PPSIE
- Status last verified
- Nov 2026
- First submitted
- 21 Oct 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Profiling Among Patients Suspected of Infective Endocarditis - PPSIE Comparing Metabolomes of Bloodstream Infections Versus Infective Endocarditis
- ClinicalTrials.gov ID
- NCT07917325
- Acronym / sponsor ID
- PPSIE / 49RC24_0250
- Conditions
- Infective Endocarditis (IE)
- Keywords
- Infective endocarditis (IE), bacteriema, metabolomic profile
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- Nov 2026 (estimated)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 4 Nov 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients included in the study | Experimental | Procedure: Blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood sampleBlood sample | Procedure or surgery | Patients included in the study |
Primary outcome
Metabolomic signature
Time frame: 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).
4 secondary outcomes
Identify potential biomarkers (BM) that can distinguish patients with BaSAC from those with EI.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Month 3 after enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sample in people with Infective Endocarditis (IE), run by University Hospital, Angers at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vincent Dubée, Pr (02 41 35 36 37 ext. +33, Vincent.Dubee@chu-angers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolomic signature (time frame: Day 1 and Day 5 after enrollement). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.