Prosthetic Joint InfectionNCT04661345
Identification of Molecular Marker of Coagulase-negative Staphylococci for the Diagnosis of Prosthetic Joint Infections
An observational study of Prosthetic Joint Infection, run by I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio at 1 site in Italy.
Trial summary
One of the major causes of prosthetic joint failure is infection. Recently, coagulase-negative Staphylococci (CoNS) have been identified as emergent, nosocomial pathogens involved in subclinical prosthetic joint infections (PJIs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prosthetic Joint Infection
- What is being tested?
- Proteomic analysis of synovial fluids and Proteomic analysis of the isolated coagulase-negative Staphylococci
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 14 Oct 2020to 14 Oct 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients subjected to a revision of the articular prosthesis due to bacterial infection or to an aseptic loosening of the implant
Who may be able to join
- ≥ 18 years old patients
- Patients subjected to a revision of the articular prosthesis due to bacterial infection mediated by coagulase-negative Staphylococci (CoNS) or to an aseptic failure of the implant
- Collection of a sufficient volume of synovial fluid
- Patient consent by signing an informed consent form
Who cannot join
- Patients not fulfilling the inclusion criteria
- Collection of a hemolytic sample
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Istituto Ortopedico Galeazzi
Milan, 20161
Elena Cittera, MSc, 00390266214057, elena.cittera@grupposandonato.it
Marta Bottagisio, Ph.D.
About this study
Official title: Molecular Hallmarks of Coagulase-negative Staphylococci: Toward the Identification of Biomarkers for the Rapid Diagnosis of Subclinical Periprosthetic Joint Infections
One of the major causes of prosthetic joint failure is infection. Recently, coagulase-negative Staphylococci (CoNS) have been identified as emergent, nosocomial pathogens involved in subclinical prosthetic joint infections (PJIs). The diagnosis of PJIs mediated by CoNS is complex and demanding due to the absence of clear clinical signs derived from the host immune system response. In this scenario, the key to successful surgical treatment is the capability to differentiate between aseptic implant loosening and septic failure. Hence, the central hypothesis of this study is that proteomic analysis of the secretome of CoNS clinical isolates associated with the characterization of patient synovial fluids will reveal a panel of putative biomarkers tightly linked to PJIs. The confirmation of the presence of bacterial PJI biomarkers in synovial fluids of infected patients will pave the way for the development of a new reliable test capable of aiding in the diagnosis of subclinical PJIs.
Read the detailed description
Task 1.1: Synovial fluids will be collected from 60 patients referred to IRCCS Galeazzi Orthopedic Institute for the revision of a septic prosthesis and from 40 patients undergoing revision due to aseptic failure. The collected synovial fluids will be stored at -80°C until analysis.
According to MSIS guidelines, the measurement of CRP and ESR levels, synovial WBC count, and the microbiological culture of the explanted device and periprosthetic tissue will be conducted following routine protocols. Only synovial fluid collected from patients of the infected group diagnosed with a PJI mediated by CoNS will be eligible for subsequent proteomic analyses. Task 1.2: The secretome of at least 10 isolates of the retrieved species of CoNS will be characterized. In particular, CoNS clinical isolates will be cultured in a drip flow reactor to induce the production of biofilm and the secretome analyzed to perform the first selection of proteins of interest.
Task 2.1: Proteins extracted from the synovial fluids of patients with or without PJI will be carbamidomethylated and digested by trypsin. Thereafter, peptide mixtures will be analyzed by nano liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Label-free quantifications (LFQ) will be applied to assess the levels of proteins expressed by bacteria and secreted in patient synovial fluids.
Task 2.2: Using proteomic software (i.e. MaxQuant, Perseus, etc.), the bioinformatic analysis will be performed to determine a pool of proteins of interest present only in samples belonging to the infected group of patients which would be closely related to the presence of bacteria.
Task 3.1: Proteins of interest identified in Task 1.2 and Task 2.2 as putative biomarkers related to CoNS-mediated PJIs will be selected for targeted proteomic analyses by means of additional bioinformatic analyses.
Task 3.2: To confirm the presence of putative biomarkers defined in Task 3.1 in synovial fluid of enrolled patients, targeted proteomic analysis will be performed on all the infected/not infected samples collected in Task 1.1. Prototypic peptides for each putative biomarker will be selected by Skyline software. Ionization and fragmentation behaviors of all candidate peptides will be studied.
Task 3.3: Finally, the information from the targeted proteomic analysis will be correlated to the outcomes of the diagnosis formulated following the MSIS guidelines in order to evaluate the diagnostic value of each selected biomarker.
- Conditions
- Prosthetic Joint Infection
- Being tested
- Proteomic analysis of synovial fluids, Proteomic analysis of the isolated coagulase-negative Staphylococci
- Keywords
- Orthopedics, Proteomics, Synovial Fluids Biomarkers, Coagulase-negative Staphylococci
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proteomic analysis of synovial fluidsOther
Characterization of the proteome of infected/aseptic synovial fluid for the identification of molecular hallmarks strictly related to the presence of a bacterial infection mediated by coagulase-negative Staphylococci
Proteomic analysis of the isolated coagulase-negative StaphylococciOther
Characterization of the secretome of coagulase-negative Staphylococci isolated from infected prosthetic implants
| Study group | Role | What they receive |
|---|---|---|
| Septic group | The septic group is composed of patients with prosthetic joint infection mediated by coagulase-negative Staphylococci (CoNS) Receives: Other: Proteomic analysis of synovial fluids; Other: Proteomic analysis of the isolated coagulase-negative Staphylococci | |
| Aseptic group | The aseptic group is composed of patients with implant failure unrelated to infection. Receives: Other: Proteomic analysis of synovial fluids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of molecular hallmarks strictly related to the presence of coagulase-negative Staphylococci in synovial fluids
Characterization of the synovial fluids of septic/aseptic enrolled patients for the identification of a pool of protein of interest strictly related to the presence of coaglase-negative Staphylococci
Measured: 3 years
Secondary outcomes (1)
Proteomic analysis of coagulase-negative Staphylococci
Characterization of the secretome of CoNS clinical isolate, and the characterization of the proteome of the synovial fluids of septic/aseptic enrolled patients
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start14 Oct 2020
- Primary completion14 Sep 2023 (estimated)
- Study completion14 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prosthetic Joint InfectionStudies of the same condition, open and under way.
- More trials run by I.R.C.C.S Ospedale Galeazzi-Sant'AmbrogioThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marta Bottagisio, Ph.D., Principal investigator, IRCCS Istituto Ortopedico Galeazzi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04661345
- Sponsor's protocol ID
- SINOVIOMA
- Status last verified
- Dec 2020
- First submitted
- 3 Dec 2020
- Last updated
- 10 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Hallmarks of Coagulase-negative Staphylococci: Toward the Identification of Biomarkers for the Rapid Diagnosis of Subclinical Periprosthetic Joint Infections
- ClinicalTrials.gov ID
- NCT04661345
- Acronym / sponsor ID
- SINOVIOMA
- Conditions
- Prosthetic Joint Infection
- Keywords
- Orthopedics, Proteomics, Synovial Fluids Biomarkers, Coagulase-negative Staphylococci
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- I.R.C.C.S Ospedale Galeazzi-Sant'AmbrogioUniversity, hospital or other
- Study start
- 14 Oct 2020 (actual)
- Primary completion
- 14 Sep 2023 (estimated)
- Study completion
- 14 Oct 2023 (estimated)
- First posted
- 10 Dec 2020 (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.
One of the major causes of prosthetic joint failure is infection. Recently, coagulase-negative Staphylococci (CoNS) have been identified as emergent, nosocomial pathogens involved in subclinical prosthetic joint infections (PJIs). The diagnosis of PJIs mediated by CoNS is complex and demanding due to the absence of clear clinical signs derived from the host immune system response. In this scenario, the key to successful surgical treatment is the capability to differentiate between aseptic implant loosening and septic failure. Hence, the central hypothesis of this study is that proteomic analysis of the secretome of CoNS clinical isolates associated with the characterization of patient synovial fluids will reveal a panel of putative biomarkers tightly linked to PJIs. The confirmation of the presence of bacterial PJI biomarkers in synovial fluids of infected patients will pave the way for the development of a new reliable test capable of aiding in the diagnosis of subclinical PJIs.
Detailed description
Task 1.1: Synovial fluids will be collected from 60 patients referred to IRCCS Galeazzi Orthopedic Institute for the revision of a septic prosthesis and from 40 patients undergoing revision due to aseptic failure. The collected synovial fluids will be stored at -80°C until analysis.
According to MSIS guidelines, the measurement of CRP and ESR levels, synovial WBC count, and the microbiological culture of the explanted device and periprosthetic tissue will be conducted following routine protocols. Only synovial fluid collected from patients of the infected group diagnosed with a PJI mediated by CoNS will be eligible for subsequent proteomic analyses. Task 1.2: The secretome of at least 10 isolates of the retrieved species of CoNS will be characterized. In particular, CoNS clinical isolates will be cultured in a drip flow reactor to induce the production of biofilm and the secretome analyzed to perform the first selection of proteins of interest.
Task 2.1: Proteins extracted from the synovial fluids of patients with or without PJI will be carbamidomethylated and digested by trypsin. Thereafter, peptide mixtures will be analyzed by nano liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Label-free quantifications (LFQ) will be applied to assess the levels of proteins expressed by bacteria and secreted in patient synovial fluids.
Task 2.2: Using proteomic software (i.e. MaxQuant, Perseus, etc.), the bioinformatic analysis will be performed to determine a pool of proteins of interest present only in samples belonging to the infected group of patients which would be closely related to the presence of bacteria.
Task 3.1: Proteins of interest identified in Task 1.2 and Task 2.2 as putative biomarkers related to CoNS-mediated PJIs will be selected for targeted proteomic analyses by means of additional bioinformatic analyses.
Task 3.2: To confirm the presence of putative biomarkers defined in Task 3.1 in synovial fluid of enrolled patients, targeted proteomic analysis will be performed on all the infected/not infected samples collected in Task 1.1. Prototypic peptides for each putative biomarker will be selected by Skyline software. Ionization and fragmentation behaviors of all candidate peptides will be studied.
Task 3.3: Finally, the information from the targeted proteomic analysis will be correlated to the outcomes of the diagnosis formulated following the MSIS guidelines in order to evaluate the diagnostic value of each selected biomarker.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Septic group | – | Other: Proteomic analysis of synovial fluids, Other: Proteomic analysis of the isolated coagulase-negative StaphylococciThe septic group is composed of patients with prosthetic joint infection mediated by coagulase-negative Staphylococci (CoNS) |
| Aseptic group | – | Other: Proteomic analysis of synovial fluidsThe aseptic group is composed of patients with implant failure unrelated to infection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients subjected to a revision of the articular prosthesis due to bacterial infection or to an aseptic loosening of the implant
Key inclusion criteria (4 listed)
- ≥ 18 years old patients
- Patients subjected to a revision of the articular prosthesis due to bacterial infection mediated by coagulase-negative Staphylococci (CoNS) or to an aseptic failure of the implant
- Collection of a sufficient volume of synovial fluid
- Patient consent by signing an informed consent form
Key exclusion criteria (2 listed)
- Patients not fulfilling the inclusion criteria
- Collection of a hemolytic sample
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 |
|---|---|---|
| Proteomic analysis of synovial fluidsCharacterization of the proteome of infected/aseptic synovial fluid for the identification of molecular hallmarks strictly related to the presence of a bacterial infection mediated by coagulase-negative Staphylococci | Other | Aseptic group, Septic group |
| Proteomic analysis of the isolated coagulase-negative StaphylococciCharacterization of the secretome of coagulase-negative Staphylococci isolated from infected prosthetic implants | Other | Septic group |
Primary outcome
Identification of molecular hallmarks strictly related to the presence of coagulase-negative Staphylococci in synovial fluids
Time frame: 3 years
Characterization of the synovial fluids of septic/aseptic enrolled patients for the identification of a pool of protein of interest strictly related to the presence of coaglase-negative Staphylococci
1 secondary outcome
Proteomic analysis of coagulase-negative Staphylococci
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2020.
- Individual participant dataSharing planned: Undecided
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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.
Marta Bottagisio, Ph.D. principal investigator
IRCCS Istituto Ortopedico Galeazzi
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 Prosthetic Joint Infection, run by I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio at 1 site in Italy.
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 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: status not confirmed, as of the sponsor's last update on 10 Dec 2020. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elena Cittera, MSc (00390266214057, elena.cittera@grupposandonato.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of molecular hallmarks strictly related to the presence of coagulase-negative Staphylococci in synovial fluids (time frame: 3 years). 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 10 Dec 2020.