Bacterial and Viral InfectionsCYTOBACTNCT06155266
Combination of Leukocyte Cell Surface Biomarkers Measured by Cytometry, to Differentiate Bacterial From Viral Infections in Emergency Department: a Multicentric Cohort for the Validation of Diagnostic Performances
An observational study of Bacterial and Viral Infections, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
Trial summary
The characterization of the bacterial or viral etiology of an infectious event is required for both isolation decisions and rationale use of antibiotics. In emergency room (ER), the direct identification of the causal pathogen is rarely available in real-time. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial and Viral Infections
- What is being tested?
- 2 additional whole blood samples of 6mL each will be taken
- How many people
- 500 participants
- Where
- 3 sitesFrance
- Study dates
- 14 May 2024to 14 Aug 2025
- Phase
- Observational
- 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
Study population: Patients admitted to the ER with a suspicion of infection
Who may be able to join
- >18 year-old
- Attending one of the participant ED from Monday to Friday between 8:30 am to 3:00 pm
- With a suspicion of infection (defined by either a measured temperature above 38°C or any microbiology diagnostic test ordered during the routine care)
- Having blood sampling during routine care
- Informed and having expressed his/her non-opposition to participate
Who cannot join
- - Pregnancy
- No social insurance
- Prisoners
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, 3 recruiting
- Not yet recruiting
Service des urgences, Lariboisière
Paris, 75010
Xavier EYER, MD, xavier.eyer@aphp.fr
- Not yet recruiting
Service des urgences, Saint-Antoine
Paris, 75012
Agathe BEAUVAIS, MD, agathe.beauvais@aphp.fr
- Recruiting
Service des urgences, Pitié Salpêtrière
Paris, 75013
Laetitia VELLY, MD, laetitia.velly@aphp.fr
Pierre HAUSFATER, MD,PhD, pierre.hausfater@aphp.fr
About this study
The characterization of the bacterial or viral etiology of an infectious event is required for both isolation decisions and rationale use of antibiotics. In emergency room (ER), the direct identification of the causal pathogen is rarely available in real-time. Alternative is the identification of the host-response to either a bacterial or viral infection. One of this host-response is the expression of peripheral leukocytes cell surface markers, measured by flow cytometry. Investigators and others have reported the high diagnostic performances of combination of cell surface biomarkers to differentiate bacterial from viral infection. The CYTOBACT study aims to confirm on a 500 patients multicentric cohort (200 having already been collected during another study: SEPTIMET), the best combinations for this diagnostic issue.
The study will be conducted in 3 emergency departments of APHP hospitals network in Paris, France. Patients with a suspicion of infection will be proposed to participate. No intervention will be introduced during the routine care in the (ER) which will be let at the discretion of the treating emergency physician. During the routine blood sampling in the ER, an additional 30 ml volume of whole blood will be collected, centrifugated, aliquoted and stored at -80°C for further measurement of the expression of a panel of cell surface markers. The participants will be followed up during their hospitalization (if any) and no longer than 28 days. Clinical data at admission, usual blood tests and all microbiological investigations performed during the hospital stay will be recorded into an electronic case record form (eCRF). Based on all those recorded data (excepted the results of flow cytometry for cell surface biomarkers) 2 independent adjudicators will qualify the infectious episode into bacterial,viral or no infection, and (if any) into infection, sepsis or septic shock (according to Sepsis 3.0 definitions).
Using different "machine learning" statistical tools, all the combination of the cell surface biomarkers will be tested to select those with the highest performance to differentiate bacterial from viral infection.
Read the detailed description
Patients attending the ED of one of the participant centers for a suspicion of infection will be informed and asked to participate. After obtaining a non-opposition to participate, during the routine blood sampling performed in the ER, an additional volume of 30 ml of whole blood will be collected, aliquoted and stored at -80°C, comprising notably 12 ml of whole blood to which 1 ml of Cytodelics® Stabiliser will be added and incubated à room temperature for 10 mn before being aliquoted and stored at -80°C. The remaining whole blood will be collected on EDTA and Paxgen tubes, centrifugated, aliquoted and stored at -80°C for blood collection.
Clinical data at admission (past medical history, vital parameters, infectious source (if any), treatments delivered in the ER) will be recorded into an eCRF. The participants will be followed up until leaving the hospital and no longer than day-28. All the microbiology tests performed during the hospital stay will be also recorded into eCRF. The diagnostic performance of the combinations of cell surface markers will be evaluated against a diagnostic reference on the bacterial of viral qualification of each infectious event. This diagnostic reference will be established by an independant expert comitee after reviewing all the clinical, and biological data recorded (excepted the results of flow cytometry), in order to adjudicate between bacterial, viral or no infection, and among infected patients to classify into infection, sepsis or septic shock (sepsis 3.0).
After completing the recruitement of participants, a panel of cell surface markers will be measured by batch on a spectral cytometer, comprising notably the biomarkers of interest already published : HLA-DR, CD169 and CX3CR1 on monocytes, and MerTk, CD64 and CD24 on neutrophils.
The performances of the combinations of cell surface markers already identified in the littérature will be tested prioritarily. However, in order to refine the best combinations of biomarkers to discriminate bacterial from viral infection, machine learning algorithms like gradient boosting tree and support vector machine tools will be applied on the entire results of cell surface markers measured. The diagnostic performance will be evaluated calculating the sensitivity, specificity, area under the ROC curve of the biomarkers combinations selected.
- Conditions
- Bacterial and Viral Infections
- Being tested
- 2 additional whole blood samples of 6mL each will be taken
- Keywords
- Bacterial infection, Viral infection, Flow cytometry, HLA-DR, CD64, MerTk, CD24, CX3CR1, CD169
- Medical subject headings
- Virus Diseases, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2 additional whole blood samples of 6mL each will be takenDiagnostic test
As part of the initial blood work-up, 2 additional samples of 6mL each of whole blood will be taken, to which 1mL of Cytodelics® Stabiliser will be added. The tubes will be mixed by inverting 10 to 15 times, incubated at +20°C for 10 minutes, then transported within 1 to 2 hours at 4°C by courier to the CRB at Pitié-Salpêtrière for aliquoting and freezing at -80°C . The expression level of cell surface markers will then be measured in series on an Aurora spectral cytometer, after frozen samples (1 to 2 aliquots) have been sent from the CRB-PSL to CIMI (INSERM U1135) at -80°C approximately once a month.
Any remaining samples sent to CIMI will be destroyed once the analyses have been completed.
What is being measured
The primary outcome is the main question the study is designed to answer.
performances of cell surface markers combinations for diagnosis
area under the ROC curve of the different combinations of cell surface biomarkers for the diagnosis of bacterial or viral infection.
Measured: through study completion, an average of 15 months
Secondary outcomes (2)
performances of cell surface markers combinations for severity assesment
area under the ROC curve of the different combinations of cell surface biomarkers for the diagnosis of infetion, sepsis or septic shock
Measured: through study completion, an average of 15 months
performances of cell surface markers combinations according to the age range of participants
area under the ROC curve of the different combinations of cell surface biomarkers in the subgroups 18 to 75 year-old and >75 year-old for the diagnosis and severity assesment
Measured: through study completion, an average of 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2023
- Study start14 May 2024
- Primary completion14 Aug 2025 (estimated)
- Study completion14 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bacterial and Viral InfectionsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06155266
- Sponsor's protocol ID
- APHP231707
- Acronym
- CYTOBACT
- Status last verified
- Jan 2025
- First submitted
- 13 Nov 2023
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Leukocyte Cell Surface Biomarkers Measured by Cytometry, to Differentiate Bacterial From Viral Infections in Emergency Department: a Multicentric Cohort for the Validation of Diagnostic Performances
- ClinicalTrials.gov ID
- NCT06155266
- Acronym / sponsor ID
- CYTOBACT / APHP231707
- Conditions
- Bacterial and Viral Infections
- Keywords
- Bacterial infection, Viral infection, Flow cytometry, HLA-DR, CD64, MerTk, CD24, CX3CR1
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 14 May 2024 (actual)
- Primary completion
- 14 Aug 2025 (estimated)
- Study completion
- 14 Aug 2025 (estimated)
- First posted
- 4 Dec 2023 (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.
The characterization of the bacterial or viral etiology of an infectious event is required for both isolation decisions and rationale use of antibiotics. In emergency room (ER), the direct identification of the causal pathogen is rarely available in real-time. Alternative is the identification of the host-response to either a bacterial or viral infection. One of this host-response is the expression of peripheral leukocytes cell surface markers, measured by flow cytometry. Investigators and others have reported the high diagnostic performances of combination of cell surface biomarkers to differentiate bacterial from viral infection. The CYTOBACT study aims to confirm on a 500 patients multicentric cohort (200 having already been collected during another study: SEPTIMET), the best combinations for this diagnostic issue.
The study will be conducted in 3 emergency departments of APHP hospitals network in Paris, France. Patients with a suspicion of infection will be proposed to participate. No intervention will be introduced during the routine care in the (ER) which will be let at the discretion of the treating emergency physician. During the routine blood sampling in the ER, an additional 30 ml volume of whole blood will be collected, centrifugated, aliquoted and stored at -80°C for further measurement of the expression of a panel of cell surface markers. The participants will be followed up during their hospitalization (if any) and no longer than 28 days. Clinical data at admission, usual blood tests and all microbiological investigations performed during the hospital stay will be recorded into an electronic case record form (eCRF). Based on all those recorded data (excepted the results of flow cytometry for cell surface biomarkers) 2 independent adjudicators will qualify the infectious episode into bacterial,viral or no infection, and (if any) into infection, sepsis or septic shock (according to Sepsis 3.0 definitions).
Using different "machine learning" statistical tools, all the combination of the cell surface biomarkers will be tested to select those with the highest performance to differentiate bacterial from viral infection.
Detailed description
Patients attending the ED of one of the participant centers for a suspicion of infection will be informed and asked to participate. After obtaining a non-opposition to participate, during the routine blood sampling performed in the ER, an additional volume of 30 ml of whole blood will be collected, aliquoted and stored at -80°C, comprising notably 12 ml of whole blood to which 1 ml of Cytodelics® Stabiliser will be added and incubated à room temperature for 10 mn before being aliquoted and stored at -80°C. The remaining whole blood will be collected on EDTA and Paxgen tubes, centrifugated, aliquoted and stored at -80°C for blood collection.
Clinical data at admission (past medical history, vital parameters, infectious source (if any), treatments delivered in the ER) will be recorded into an eCRF. The participants will be followed up until leaving the hospital and no longer than day-28. All the microbiology tests performed during the hospital stay will be also recorded into eCRF. The diagnostic performance of the combinations of cell surface markers will be evaluated against a diagnostic reference on the bacterial of viral qualification of each infectious event. This diagnostic reference will be established by an independant expert comitee after reviewing all the clinical, and biological data recorded (excepted the results of flow cytometry), in order to adjudicate between bacterial, viral or no infection, and among infected patients to classify into infection, sepsis or septic shock (sepsis 3.0).
After completing the recruitement of participants, a panel of cell surface markers will be measured by batch on a spectral cytometer, comprising notably the biomarkers of interest already published : HLA-DR, CD169 and CX3CR1 on monocytes, and MerTk, CD64 and CD24 on neutrophils.
The performances of the combinations of cell surface markers already identified in the littérature will be tested prioritarily. However, in order to refine the best combinations of biomarkers to discriminate bacterial from viral infection, machine learning algorithms like gradient boosting tree and support vector machine tools will be applied on the entire results of cell surface markers measured. The diagnostic performance will be evaluated calculating the sensitivity, specificity, area under the ROC curve of the biomarkers combinations selected.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to the ER with a suspicion of infection
Key inclusion criteria (5 listed)
- >18 year-old
- Attending one of the participant ED from Monday to Friday between 8:30 am to 3:00 pm
- With a suspicion of infection (defined by either a measured temperature above 38°C or any microbiology diagnostic test ordered during the routine care)
- Having blood sampling during routine care
- Informed and having expressed his/her non-opposition to participate
Key exclusion criteria (3 listed)
- - Pregnancy
- No social insurance
- Prisoners
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 |
|---|---|---|
| 2 additional whole blood samples of 6mL each will be takenAs part of the initial blood work-up, 2 additional samples of 6mL each of whole blood will be taken, to which 1mL of Cytodelics® Stabiliser will be added. The tubes will be mixed by inverting 10 to 15 times, incubated at +20°C for 10 minutes, then transported within 1 to 2 hours at 4°C by courier to the CRB at Pitié-Salpêtrière for aliquoting and freezing at -80°C . The expression level of cell surface markers will then be measured in series on an Aurora spectral cytometer, after frozen samples (1 to 2 aliquots) have been sent from the CRB-PSL to CIMI (INSERM U1135) at -80°C approximately once a month. Any remaining samples sent to CIMI will be destroyed once the analyses have been completed. | Diagnostic test | – |
Primary outcome
performances of cell surface markers combinations for diagnosis
Time frame: through study completion, an average of 15 months
area under the ROC curve of the different combinations of cell surface biomarkers for the diagnosis of bacterial or viral infection.
2 secondary outcomes
performances of cell surface markers combinations for severity assesment
Time frame: through study completion, an average of 15 months
performances of cell surface markers combinations according to the age range of participants
Time frame: through study completion, an average of 15 months
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 13 Jan 2025.
- Individual participant dataSharing planned: Yes. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations
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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?
An observational study of Bacterial and Viral Infections, run by Assistance Publique - Hôpitaux de Paris 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 5 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 13 Jan 2025. 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 laetitia Velly, MD ((33)7 82 28 94 91, laetitia.velly@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
performances of cell surface markers combinations for diagnosis (time frame: through study completion, an average of 15 months). 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 13 Jan 2025.