Fractures, BoneMETADIAGNCT05770856
Clinical Metagenomic of Post-traumatic Infections
An observational study of Fractures, Bone and Infections, run by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer at 1 site in France.
Trial summary
Treatment of fracture related infection is challenging and often lead to failure in such situation that carry a high health cost burden. These infections are often polymicrobial, making the identification of all involved microorganisms a major concern to provide tailored antibiotic treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fractures, Bone, Infections
- What is being tested?
- Metagenomic sequencing
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 27 Apr 2023to 15 Jul 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
- Adult, Older adult
Study population: Patients admitted to hospital for trauma for which an infection of the traumatic site was diagnosed
Who may be able to join
- Age ≥ 18 years
- Diagnosis of trauma-related infection
Who cannot join
- Participation in an interventional research during the study
- Patient opposition
- Absence of bone or soft tissue samples stored at -80°C
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Metagenomic Next-Generation Sequencing for Microbial Infections in Trauma
Treatment of fracture related infection is challenging and often lead to failure in such situation that carry a high health cost burden.
These infections are often polymicrobial, making the identification of all involved microorganisms a major concern to provide tailored antibiotic treatment. Culture-independent methods are needed to better represent the microbial diversity of infected wounds. Metagenomic sequencing might lead to an accurate microbiome characterization in infected trauma-related wound.
Read more
Preliminary studies have reported results of metagenomic sequencing in diabetic foot infection but data focusing on non-diabetic infected patients are scarce.
The impact of post-traumatic infected wound microbiome needs to be assessed, with regards to bacterial abundance, diversity including at the strain level and functional genes, along with their longitudinal evolution and association with clinical outcomes.
Read the detailed description
DNA will be extracted from samples carried out during surgical procedures. Different extraction protocols will be assessed to determine the best to be used for this type of tissue samples.
Purified DNA will be quantified using the Qubit dsDNA High-Sensitivity Assay Kit (Invitrogen). The quality of the fragment length will be estimated with the DNA high-sensitivity kit in the 2100 Bioanalyzer (Agilent Technologies). DNA sequencing will be performed with Oxford Nanopore Technologie devices: MinIONTM and GridIONTM.
Another sequencing of the same samples will be performed on the MiSeq after libraries preparation using the NexteraXT DNA Library Preparation Kit (Illumina).
Sequenced OTU from both sequencing methods will be confronted at different taxonomic ranks and compared with conventional routine method results (bacterial culture). A functional analysis of sequences will be done to identify potential genes associated with clinical outcome.
- Conditions
- Fractures, Bone, Infections
- Being tested
- Metagenomic sequencing
- Keywords
- High throughput sequencing, Nanopore, Diagnosis, Trauma, Microbiome, Infection
- Medical subject headings
- Fractures, Bone, Infections, Disease, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metagenomic sequencingDiagnostic test
Samples shall be submitted to high throughput sequencing using both illumine MiSeq and Oxford Nanopore Technologies.
| Study group | Role | What they receive |
|---|---|---|
| Trauma related infection | Not described Receives: Diagnostic Test: Metagenomic sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microbiome of fracture-related and other trauma-related infection
Metagenomic sequencing will be used to determine the microbiome of trauma-related infections using Illumina MiSeq and Oxford Nanopore Technologies.
Data will be compared with those from reference microbiological identification techniques (culture).
Measured: About 2 months
Secondary outcomes (3)
Comparison of high throughput sequencing techniques yield
The FRI-associated microbiomes composition obtained with each sequencing methods will be compared in terms of abundance and variety (K coefficient and frequency)
Measured: About 3 months
Number and nature of virulence or resistance factors among identified OTU (operational Taxonomic Unit)
Functional annotation of sequenced bacterial genomes to assess the presence of virulence and/or resistance-associated factors, using Prokka software.
Measured: About 6 months
Number of bacteria and their relative abundance according to patients' outcome using the EBJIS (European Bone and Joint Infection) definition
To determine the association of the NGS-based microbiome longtitudinal composition in terms of variety (number of OTU) and abundance (number of reads) with infection persistence according to the EBJIS (European Bone and Joint Infection) definition.
Measured: About 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2023
- Study start27 Apr 2023
- Primary completion15 Jul 2023
- Study completion15 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Fractures, BoneStudies 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
- Retrospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
- Sponsor type
- University, hospital or other
- Collaborators
- Sainte-Anne Military Teaching Hospital, UMR Vitrome, IRD 257
- Responsible party
- Sponsor
- Investigators
- David LACÔTE-DELARBRE, MD, Study director, Sainte-Anne Military Teaching Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05770856
- Sponsor's protocol ID
- 2023-CHITS-003
- Acronym
- METADIAG
- Status last verified
- Jul 2024
- First submitted
- 7 Feb 2023
- Last updated
- 29 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ivy MI, Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, Hanssen AD, Abdel MP, Chia N, Yao JZ, Tande AJ, Mandrekar JN, Patel R. Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing. J Clin Microbiol. 2018 Aug 27;56(9):e00402-18. doi: 10.1128/JCM.00402-18. Print 2018 Sep.
PubMed 29848568Jnana A, Muthuraman V, Varghese VK, Chakrabarty S, Murali TS, Ramachandra L, Shenoy KR, Rodrigues GS, Prasad SS, Dendukuri D, Morschhauser A, Nestler J, Peter H, Bier FF, Satyamoorthy K. Microbial Community Distribution and Core Microbiome in Successive Wound Grades of Individuals with Diabetic Foot Ulcers. Appl Environ Microbiol. 2020 Mar 2;86(6):e02608-19. doi: 10.1128/AEM.02608-19. Print 2020 Mar 2.
PubMed 31924616Kalan LR, Meisel JS, Loesche MA, Horwinski J, Soaita I, Chen X, Uberoi A, Gardner SE, Grice EA. Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy. Cell Host Microbe. 2019 May 8;25(5):641-655.e5. doi: 10.1016/j.chom.2019.03.006. Epub 2019 Apr 18.
PubMed 31006638Mudrik-Zohar H, Carasso S, Gefen T, Zalmanovich A, Katzir M, Cohen Y, Paitan Y, Geva-Zatorsky N, Chowers M. Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods. Front Cell Infect Microbiol. 2022 Mar 24;12:836699. doi: 10.3389/fcimb.2022.836699. eCollection 2022.
PubMed 35402307Delarbre D, Lavrard P, Elias A, Bossi V, Kacel I, Janvier F, Fournier PE. Bacterial DNA enrichment for low-inoculum fracture-related infection diagnostic using high-throughput sequencing. Diagn Microbiol Infect Dis. 2024 Sep;110(1):116411. doi: 10.1016/j.diagmicrobio.2024.116411. Epub 2024 Jun 22.
PubMed 39018934
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Metagenomic Next-Generation Sequencing for Microbial Infections in Trauma
- ClinicalTrials.gov ID
- NCT05770856
- Acronym / sponsor ID
- METADIAG / 2023-CHITS-003
- Conditions
- Fractures, Bone, Infections
- Keywords
- High throughput sequencing, Nanopore, Diagnosis, Trauma, Microbiome, Infection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Centre Hospitalier Intercommunal de Toulon La Seyne sur MerUniversity, hospital or other
- Collaborators
- Sainte-Anne Military Teaching Hospital, UMR Vitrome, IRD 257
- Study start
- 27 Apr 2023 (actual)
- Primary completion
- 15 Jul 2023 (actual)
- Study completion
- 15 Jul 2023 (actual)
- First posted
- 16 Mar 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.
Treatment of fracture related infection is challenging and often lead to failure in such situation that carry a high health cost burden.
These infections are often polymicrobial, making the identification of all involved microorganisms a major concern to provide tailored antibiotic treatment. Culture-independent methods are needed to better represent the microbial diversity of infected wounds. Metagenomic sequencing might lead to an accurate microbiome characterization in infected trauma-related wound.
Preliminary studies have reported results of metagenomic sequencing in diabetic foot infection but data focusing on non-diabetic infected patients are scarce.
The impact of post-traumatic infected wound microbiome needs to be assessed, with regards to bacterial abundance, diversity including at the strain level and functional genes, along with their longitudinal evolution and association with clinical outcomes.
Detailed description
DNA will be extracted from samples carried out during surgical procedures. Different extraction protocols will be assessed to determine the best to be used for this type of tissue samples.
Purified DNA will be quantified using the Qubit dsDNA High-Sensitivity Assay Kit (Invitrogen). The quality of the fragment length will be estimated with the DNA high-sensitivity kit in the 2100 Bioanalyzer (Agilent Technologies). DNA sequencing will be performed with Oxford Nanopore Technologie devices: MinIONTM and GridIONTM.
Another sequencing of the same samples will be performed on the MiSeq after libraries preparation using the NexteraXT DNA Library Preparation Kit (Illumina).
Sequenced OTU from both sequencing methods will be confronted at different taxonomic ranks and compared with conventional routine method results (bacterial culture). A functional analysis of sequences will be done to identify potential genes associated with clinical outcome.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trauma related infection | – | Diagnostic Test: Metagenomic sequencing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to hospital for trauma for which an infection of the traumatic site was diagnosed
Key inclusion criteria (2 listed)
- Age ≥ 18 years
- Diagnosis of trauma-related infection
Key exclusion criteria (3 listed)
- Participation in an interventional research during the study
- Patient opposition
- Absence of bone or soft tissue samples stored at -80°C
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 |
|---|---|---|
| Metagenomic sequencingSamples shall be submitted to high throughput sequencing using both illumine MiSeq and Oxford Nanopore Technologies. | Diagnostic test | Trauma related infection |
Primary outcome
Microbiome of fracture-related and other trauma-related infection
Time frame: About 2 months
Metagenomic sequencing will be used to determine the microbiome of trauma-related infections using Illumina MiSeq and Oxford Nanopore Technologies. Data will be compared with those from reference microbiological identification techniques (culture).
3 secondary outcomes
Comparison of high throughput sequencing techniques yield
Time frame: About 3 months
Number and nature of virulence or resistance factors among identified OTU (operational Taxonomic Unit)
Time frame: About 6 months
Number of bacteria and their relative abundance according to patients' outcome using the EBJIS (European Bone and Joint Infection) definition
Time frame: About 6 months
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 29 Jul 2024.
- Background: PubMed 29848568Ivy MI, Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, Hanssen AD, Abdel MP, Chia N, Yao JZ, Tande AJ, Mandrekar JN, Patel R. Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing. J Clin Microbiol. 2018 Aug 27;56(9):e00402-18. doi: 10.1128/JCM.00402-18. Print 2018 Sep.
- Background: PubMed 31924616Jnana A, Muthuraman V, Varghese VK, Chakrabarty S, Murali TS, Ramachandra L, Shenoy KR, Rodrigues GS, Prasad SS, Dendukuri D, Morschhauser A, Nestler J, Peter H, Bier FF, Satyamoorthy K. Microbial Community Distribution and Core Microbiome in Successive Wound Grades of Individuals with Diabetic Foot Ulcers. Appl Environ Microbiol. 2020 Mar 2;86(6):e02608-19. doi: 10.1128/AEM.02608-19. Print 2020 Mar 2.
- Background: PubMed 31006638Kalan LR, Meisel JS, Loesche MA, Horwinski J, Soaita I, Chen X, Uberoi A, Gardner SE, Grice EA. Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy. Cell Host Microbe. 2019 May 8;25(5):641-655.e5. doi: 10.1016/j.chom.2019.03.006. Epub 2019 Apr 18.
- Background: PubMed 35402307Mudrik-Zohar H, Carasso S, Gefen T, Zalmanovich A, Katzir M, Cohen Y, Paitan Y, Geva-Zatorsky N, Chowers M. Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods. Front Cell Infect Microbiol. 2022 Mar 24;12:836699. doi: 10.3389/fcimb.2022.836699. eCollection 2022.
- Results publication: PubMed 39018934Delarbre D, Lavrard P, Elias A, Bossi V, Kacel I, Janvier F, Fournier PE. Bacterial DNA enrichment for low-inoculum fracture-related infection diagnostic using high-throughput sequencing. Diagn Microbiol Infect Dis. 2024 Sep;110(1):116411. doi: 10.1016/j.diagmicrobio.2024.116411. Epub 2024 Jun 22.
- Individual participant dataSharing planned: No
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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.
David LACÔTE-DELARBRE, MD study director
Sainte-Anne Military Teaching Hospital
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 Fractures, Bone and Infections, run by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer 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 2 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: finished, as of the sponsor's last update on 29 Jul 2024. 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?
Microbiome of fracture-related and other trauma-related infection (time frame: About 2 months). 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 NCT05770856, which also lists 5 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 29 Jul 2024.