SIRSCaptainNCT01378169
SIRS and Bacterial Sepsis Discrimination by Biomarkers in ICU
An observational study of SIRS and Sepsis, run by Fondation Hôpital Saint-Joseph at 1 site in France.
Trial summary
Aim of the study : The primary aim of the investigators study is to highlight the presence of biomarkers (biological indicators of the presence of inflammation or infection) of infectious processes during the systemic inflammatory response (SIRS) allowing, first to discriminate non-infectious inflammation from… Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- SIRS, Sepsis, Severe Sepsis
- How many people
- 300 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2011to 1 Jun 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: ICU patients whatever was their admission indication presenting a SIRS with or without sepsis.
Who may be able to join
- Age> = 18 years
- Patient hospitalized in ICU with a diagnosis of SIRS:
- Temperatures above 38 ° C or below 36 ° C
- At least one other criterion from:
- Heart rate> 90 bpm
- Respiratory rate above 20 breaths / min or PaCO2 <32 mmHg
Show all 9Show fewer
- Leukocytosis greater than or less than 4000/mm3 12000/m3
- Patient admitted in intensive care for less than 12 hours
- Patient does not preclude its participation in the study.
Who cannot join
- Decision to limit treatment before potential inclusion in the study
- No affiliation to a social security scheme (beneficiary or assignee)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Detection and Diagnostic Performance of Bio-markers During Bacterial Sepsis: Multicentre Cohort Study in Intensive Care
Aim of the study : The primary aim of the investigators study is to highlight the presence of biomarkers (biological indicators of the presence of inflammation or infection) of infectious processes during the systemic inflammatory response (SIRS) allowing, first to discriminate non-infectious inflammation from infectious processes and secondary to determine the microbial pathogen responsive of the infection. For this purpose the investigators will conduct a combinatorial approach of several blood markers including usual markers of inflammation and other blood and cells markers. Expression of small pieces of RNA (miRNA) known to inhibit determined gene expression, will also be analysed in monocytes (a specific group of white blood cells involved in the fist line of defences against microbes.
Study design : For this purpose the investigators will include 300 patients admitted to the intensive care unit with suspicion of infection. Serial blood sample will be take for biological parameters analysis. Efficiency of each single parameters and of different combinations of different markers to determine the presence or absence of infection responsive of clinical inflammation will be studied.
Read the detailed description
Aim of the study : The project's main objective is the establishment of the diagnostic performance of the association of diagnostic markers of infectious processes linked to the pathogen or host during the systemic inflammatory response syndromes (SIRS) in critical care patients allowing, first to discriminate non infectious SIRS from sepsis and, secondary to determine the microbial pathogen responsive of the inflammation. For this purpose, we will conduct a combinatorial approach of several plasma markers including usual markers (CRP, PCT, other soluble mediators (soluble TREM-1, IL-6, IL-1Ra, IL-10, CXCL2, CXCL8, CCL2 and CCL5), cell markers (CD14 / HLA-DR expression on monocytes and TLR2, 4, 9 expression on NK cells) together with modified expression of microRNA (miRNA) in circulating monocytes.
Study design : This study will include patients admitted to the ICU with SIRS and suspected sepsis, according to usual criteria. Infection definition will be based on a combination clinical, bacteriological and cyto-or histo-pathological according to the disease involved.
A serial measurement of biological parameters previously described will be realized from D0 to D3.
Evaluation criteria : The primary endpoint is to determine the ability of each individual parameter and of the different combination to discriminate between sepsis and noninfectious inflammation. The diagnostic performance of biomarkers studied will be done by calculating the sensitivity, specificity, positive and negative predictive value of each test alone or in combination with respect to the existence of an infection (sepsis) or not (SIRS). According to data from the literature and our own experience, the expected proportion of patients with sepsis among the holders of SIRS was 50%. The discriminatory ability of each test will be performed by using ROC curves and calibration using the Hosmer-Lemeshow several layers of increasing severity. The level of service provided is a p-value <5%. There are no plans to statistical criteria for stopping the search in case of biological data missing.
The value of the area under the ROC curve (AUC) of the PCT is 78% (95% CI 69-77). Assuming that one of the tests or combinatorial approach will increase the AUC to 85%, the number of patients needed for this study is estimated to be 300.
Conduct of research : Study will be conducted in 5 different sites. Patients admitted with or who develop a SIRS during hospitalization will be included. There will be nothing peculiar in the therapeutic management and patients will be covert by the international guidelines.
- Inclusion criteria:
- Patient admitted with or who develop SIRS during ICU hospitalisation
- Two or more parameter of the SIRS definition
- Patient does not preclude its participation in the study
- Non inclusion criteria
- Decision of withdrawal or withholding therapeutic interventions
- No affiliation to a social security scheme
The measurement of biological endpoints will be conducted once daily, from D0 (admission) to D2 using a blood sample. The study of monocyte expression of miRNA will be performed on a portion of the cohort, corresponding to patients selected on the St. Joseph site (intensive care unit and surgical intensive care unit) because of complexity to implement, and cost level (requiring specific funding).
Total projected duration of the search: The recruitment period will run for 23 months with the aim to include all 300 patients. Patients included in the research will be followed until day 28 or day of hospital leaving, if earlier.
Stopping rules of the study to a patient: patient can discontinue their participation at any time during the research.
Security evaluation : Being a non-interventional study (biological collection) in the usual care of patients, no serious adverse event is expected to be related to research.
Any new data security, potentially leading to a reassessment of the benefits and risks of research, or which may be sufficient to consider changes in the conduct of research must be reported.
- Conditions
- SIRS, Sepsis, Severe Sepsis, Septic Shock
- Keywords
- SIRS, Sepsis, Severe Sepsis, Septic Shock, Inflammatory processes, Cytokines, HLA-DR, HLA type II, Chemokines, TLR expression, mRNA expression in whole blood, Bacterial DNA detection, Prognosis factors, Infection, Diagnosis
- Medical subject headings
- Sepsis, Shock, Septic, Infections, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SIRS patients | Every patient, without exclusion criteria, presenting with SIRS during an hospitalization in ICU. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combination of biomarkers in sepsis
The primary endpoint is to determine the ability of each individual parameter and of the different combination to discriminate between sepsis and noninfectious inflammation.
Each biomarker will be isolatelly studied to determine existence of a cut-off value allowing discrimination between SIRS and sepsis.
Each positive biomarker (biomarker for which such a cut-off can be determined), will be include in a second study involving all or part of the positive biomarkers to determine the possibility of increasing AUC for discrimination of SIRS and sepsis patients
Measured: 3 days ( from D0 to D2)
Secondary outcomes (2)
Pathogen in human fluids (Blood, BAL, CSF, Urin)
A partnership with Biomerieux laboratory was estabished to allow microbial detection at D0 by a new system of microbial DNA amplification, which is at the moment under development
Measured: D0
mRNA expression during inflammatory process in white blood cells
Study of modification of mRNA expression between SIRS and sepsis during inflammatory process in white blood cells. Study of the expression of whole mRNA in whole blood and of its modification during the 3 fist days of SIRS to determine a potential specific profil during infectious processes
Measured: D0 to D3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2011 (estimated)
- Study start1 Jan 2011
- Primary completion1 Jan 2013
- Study completion1 Jun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for SIRSStudies of the same condition, open and under way.
- 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
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Collaborators
- BioMérieux, Institut Pasteur, Assistance Publique - Hôpitaux de Paris
- Responsible party
- Sponsor
- Investigators
- François J Philippart, MD; PhD, Principal investigator, Fondation Hôpital Saint-Joseph
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01378169
- Sponsor's protocol ID
- AOM09143
- Other IDs
- N° 2010-A00908-31
- Acronym
- Captain
- Status last verified
- Mar 2017
- First submitted
- 9 May 2011
- Last updated
- 17 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005 Jan 1-7;365(9453):63-78. doi: 10.1016/S0140-6736(04)17667-8.
PubMed 15639681Gibot S, Cravoisy A, Levy B, Bene MC, Faure G, Bollaert PE. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med. 2004 Jan 29;350(5):451-8. doi: 10.1056/NEJMoa031544.
PubMed 14749453Adib-Conquy M, Monchi M, Goulenok C, Laurent I, Thuong M, Cavaillon JM, Adrie C. Increased plasma levels of soluble triggering receptor expressed on myeloid cells 1 and procalcitonin after cardiac surgery and cardiac arrest without infection. Shock. 2007 Oct;28(4):406-10. doi: 10.1097/shk.0b013e3180488154.
PubMed 17558349Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D. Cytokine cascade in sepsis. Scand J Infect Dis. 2003;35(9):535-44. doi: 10.1080/00365540310015935.
PubMed 14620132Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation. 2002 Jul 30;106(5):562-8. doi: 10.1161/01.cir.0000023891.80661.ad.
PubMed 12147537Monneret G, Lepape A, Voirin N, Bohe J, Venet F, Debard AL, Thizy H, Bienvenu J, Gueyffier F, Vanhems P. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med. 2006 Aug;32(8):1175-83. doi: 10.1007/s00134-006-0204-8. Epub 2006 Jun 2.
PubMed 16741700Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest. 1991 Nov;88(5):1747-54. doi: 10.1172/JCI115493.
PubMed 1939659Misset B, Philippart F, Fitting C, Bedos JP, Diehl JL, Hamzaoui O, Annane D, Journois D, Parlato M, Moucadel V, Cavaillon JM, Coste J; CAPTAIN Study Group. Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study. PLoS One. 2022 Oct 27;17(10):e0267517. doi: 10.1371/journal.pone.0267517. eCollection 2022.
PubMed 36301921
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection and Diagnostic Performance of Bio-markers During Bacterial Sepsis: Multicentre Cohort Study in Intensive Care
- ClinicalTrials.gov ID
- NCT01378169
- Acronym / sponsor ID
- Captain / AOM09143
- Conditions
- SIRS, Sepsis, Severe Sepsis, Septic Shock
- Keywords
- SIRS, Sepsis, Severe Sepsis, Septic Shock, Inflammatory processes, Cytokines, HLA-DR, HLA type II
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Collaborators
- BioMérieux, Institut Pasteur, Assistance Publique - Hôpitaux de Paris
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 1 Jan 2013 (actual)
- Study completion
- 1 Jun 2013 (actual)
- First posted
- 22 Jun 2011 (estimated)
- 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.
Aim of the study : The primary aim of the investigators study is to highlight the presence of biomarkers (biological indicators of the presence of inflammation or infection) of infectious processes during the systemic inflammatory response (SIRS) allowing, first to discriminate non-infectious inflammation from infectious processes and secondary to determine the microbial pathogen responsive of the infection. For this purpose the investigators will conduct a combinatorial approach of several blood markers including usual markers of inflammation and other blood and cells markers. Expression of small pieces of RNA (miRNA) known to inhibit determined gene expression, will also be analysed in monocytes (a specific group of white blood cells involved in the fist line of defences against microbes.
Study design : For this purpose the investigators will include 300 patients admitted to the intensive care unit with suspicion of infection. Serial blood sample will be take for biological parameters analysis. Efficiency of each single parameters and of different combinations of different markers to determine the presence or absence of infection responsive of clinical inflammation will be studied.
Detailed description
Aim of the study : The project's main objective is the establishment of the diagnostic performance of the association of diagnostic markers of infectious processes linked to the pathogen or host during the systemic inflammatory response syndromes (SIRS) in critical care patients allowing, first to discriminate non infectious SIRS from sepsis and, secondary to determine the microbial pathogen responsive of the inflammation. For this purpose, we will conduct a combinatorial approach of several plasma markers including usual markers (CRP, PCT, other soluble mediators (soluble TREM-1, IL-6, IL-1Ra, IL-10, CXCL2, CXCL8, CCL2 and CCL5), cell markers (CD14 / HLA-DR expression on monocytes and TLR2, 4, 9 expression on NK cells) together with modified expression of microRNA (miRNA) in circulating monocytes.
Study design : This study will include patients admitted to the ICU with SIRS and suspected sepsis, according to usual criteria. Infection definition will be based on a combination clinical, bacteriological and cyto-or histo-pathological according to the disease involved.
A serial measurement of biological parameters previously described will be realized from D0 to D3.
Evaluation criteria : The primary endpoint is to determine the ability of each individual parameter and of the different combination to discriminate between sepsis and noninfectious inflammation. The diagnostic performance of biomarkers studied will be done by calculating the sensitivity, specificity, positive and negative predictive value of each test alone or in combination with respect to the existence of an infection (sepsis) or not (SIRS). According to data from the literature and our own experience, the expected proportion of patients with sepsis among the holders of SIRS was 50%. The discriminatory ability of each test will be performed by using ROC curves and calibration using the Hosmer-Lemeshow several layers of increasing severity. The level of service provided is a p-value <5%. There are no plans to statistical criteria for stopping the search in case of biological data missing.
The value of the area under the ROC curve (AUC) of the PCT is 78% (95% CI 69-77). Assuming that one of the tests or combinatorial approach will increase the AUC to 85%, the number of patients needed for this study is estimated to be 300.
Conduct of research : Study will be conducted in 5 different sites. Patients admitted with or who develop a SIRS during hospitalization will be included. There will be nothing peculiar in the therapeutic management and patients will be covert by the international guidelines.
- Inclusion criteria:
- Patient admitted with or who develop SIRS during ICU hospitalisation
- Two or more parameter of the SIRS definition
- Patient does not preclude its participation in the study
- Non inclusion criteria
- Decision of withdrawal or withholding therapeutic interventions
- No affiliation to a social security scheme
The measurement of biological endpoints will be conducted once daily, from D0 (admission) to D2 using a blood sample. The study of monocyte expression of miRNA will be performed on a portion of the cohort, corresponding to patients selected on the St. Joseph site (intensive care unit and surgical intensive care unit) because of complexity to implement, and cost level (requiring specific funding).
Total projected duration of the search: The recruitment period will run for 23 months with the aim to include all 300 patients. Patients included in the research will be followed until day 28 or day of hospital leaving, if earlier.
Stopping rules of the study to a patient: patient can discontinue their participation at any time during the research.
Security evaluation : Being a non-interventional study (biological collection) in the usual care of patients, no serious adverse event is expected to be related to research.
Any new data security, potentially leading to a reassessment of the benefits and risks of research, or which may be sufficient to consider changes in the conduct of research must be reported.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIRS patients | – | –Every patient, without exclusion criteria, presenting with SIRS during an hospitalization in ICU. |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- ICU patients whatever was their admission indication presenting a SIRS with or without sepsis.
Key inclusion criteria (9 listed)
- Age> = 18 years
- Patient hospitalized in ICU with a diagnosis of SIRS:
- Temperatures above 38 ° C or below 36 ° C
- Heart rate> 90 bpm
- Respiratory rate above 20 breaths / min or PaCO2 <32 mmHg
Key exclusion criteria (2 listed)
- Decision to limit treatment before potential inclusion in the study
- No affiliation to a social security scheme (beneficiary or assignee)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Combination of biomarkers in sepsis
Time frame: 3 days ( from D0 to D2)
The primary endpoint is to determine the ability of each individual parameter and of the different combination to discriminate between sepsis and noninfectious inflammation. Each biomarker will be isolatelly studied to determine existence of a cut-off value allowing discrimination between SIRS and sepsis. Each positive biomarker (biomarker for which such a cut-off can be determined), will be include in a second study involving all or part of the positive biomarkers to determine the possibility of increasing AUC for discrimination of SIRS and sepsis patients
2 secondary outcomes
Pathogen in human fluids (Blood, BAL, CSF, Urin)
Time frame: D0
mRNA expression during inflammatory process in white blood cells
Time frame: D0 to D3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2017.
- Background: PubMed 15639681Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005 Jan 1-7;365(9453):63-78. doi: 10.1016/S0140-6736(04)17667-8.
- Background: PubMed 14749453Gibot S, Cravoisy A, Levy B, Bene MC, Faure G, Bollaert PE. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med. 2004 Jan 29;350(5):451-8. doi: 10.1056/NEJMoa031544.
- Background: PubMed 17558349Adib-Conquy M, Monchi M, Goulenok C, Laurent I, Thuong M, Cavaillon JM, Adrie C. Increased plasma levels of soluble triggering receptor expressed on myeloid cells 1 and procalcitonin after cardiac surgery and cardiac arrest without infection. Shock. 2007 Oct;28(4):406-10. doi: 10.1097/shk.0b013e3180488154.
- Background: PubMed 14620132Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D. Cytokine cascade in sepsis. Scand J Infect Dis. 2003;35(9):535-44. doi: 10.1080/00365540310015935.
- Background: PubMed 12147537Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation. 2002 Jul 30;106(5):562-8. doi: 10.1161/01.cir.0000023891.80661.ad.
- Background: PubMed 16741700Monneret G, Lepape A, Voirin N, Bohe J, Venet F, Debard AL, Thizy H, Bienvenu J, Gueyffier F, Vanhems P. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med. 2006 Aug;32(8):1175-83. doi: 10.1007/s00134-006-0204-8. Epub 2006 Jun 2.
- Background: PubMed 1939659Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest. 1991 Nov;88(5):1747-54. doi: 10.1172/JCI115493.
- Derived from this study: PubMed 36301921Misset B, Philippart F, Fitting C, Bedos JP, Diehl JL, Hamzaoui O, Annane D, Journois D, Parlato M, Moucadel V, Cavaillon JM, Coste J; CAPTAIN Study Group. Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study. PLoS One. 2022 Oct 27;17(10):e0267517. doi: 10.1371/journal.pone.0267517. eCollection 2022.
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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. This study is not recruiting at the moment.
François J Philippart, MD; PhD principal investigator
Fondation Hôpital Saint-Joseph
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SIRS and Sepsis, run by Fondation Hôpital Saint-Joseph at 1 site 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 9 inclusion and 2 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: finished, as of the sponsor's last update on 17 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combination of biomarkers in sepsis (time frame: 3 days ( from D0 to D2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01378169, which also lists 8 linked publications.
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 17 Oct 2017.