Pleural InfectionTORPIDS-2NCT06513689
The Oxford Pleural Infection Endotyping Study
An observational study of Pleural Infection and Pleural Diseases, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Pleural infection is a severe disease with increasing incidence worldwide. The subphenotypes of pleural infection remain unknown.We designed a study to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Infection, Pleural Diseases, Pleural Effusion
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Jun 2021to 20 Jun 2024
- 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 with evidence of pleural infection
Samples collected for the PILOT clinical trial (DOI: 10.1183/13993003.00130-2020) used for the TORPIDS-2 study.
Patients were included if they had a clinical presentation consistent with pleural infection and any of the following criteria: 1. pleural fluid that was macroscopically purulent; or 2. pleural fluid that was positive on culture for bacterial infection; or 3. pleural fluid that demonstrated bacteria on Gram staining; or 4. pleural fluid with a pH ≤7.2 (measured by blood gas analyser) or low glucose level (≤3 mmol·L-1 or ≤55 mg·dL-1) in a patient with clinical evidence of infection; or 5. contrast-enhanced computed tomography (CT) evidence of pleural infection (consolidation of underlying lung with enhancing pleural collection) in a patient with clinical evidence of infection, alongside exclusion of other sources of infection. Evidence of infection was assessed by the recruiting physician on the basis of fever, an elevated peripheral blood white-cell count, or elevated serum inflammatory markers such as C-reactive protein (CRP). Study exclusion criteria were as follows: 1. age <18 years; 2. no pleural fluid available for analysis; 3. previous pneumonectomy on the side of pleural infection; and 4. expected survival of <3 months due to co-morbid disease, as judged by the recruiting physician.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Laboratory of Pleural Translational Research, Nuffield Department of Medicine, University of Oxford
Oxford, Oxfordshire, OX3 7FZ
About this study
Official title: Pleural Fluid Proteomics From Patients With Pleural Infection Shows Signatures of Diverse Neutrophilic Responses: The Oxford Pleural Infection Endotyping Study (TORPIDS 2)
Pleural infection is a severe disease with increasing incidence worldwide. The subphenotypes of pleural infection remain unknown.We designed a study to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome.
We subjected 80 pleural fluid samples to unlabelled mass spectrometry.
Read more
Pathway analysis of the differentially expressed proteins identified the neutrophil degranulation, glycolysis, pentose phosphate pathway, and the liver and retinoid X receptors (LXR-RXR) activation. Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation.
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation.
Read the detailed description
Pleural infection is a common and severe disease with increasing incidence worldwide. The endotypes of pleural infection remain unknown. A better understanding of patient variation in underlying biological response to infection may lead to improved treatments and clinical outcomes. We designed a study with the aim to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome.
We subjected 80 pleural fluid samples from the PILOT study, a prospective study on pleural infection, to unlabelled mass spectrometry. Proteins were retained if they were detected in at least 50% of the samples resulting in a total of 449 proteins. Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples, Spearman and exact Fischer's methods were used for correlation assessment and protein expression was correlated with clinical outcomes.
UMAP plotting separated the samples in to two different and distinct cohorts. Pathway analysis of the differentially expressed proteins identified neutrophil degranulation, glycolysis, the pentose phosphate pathway, and the liver and retinoid X receptors (LXR-RXR) activation. Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation. Specimens dominated by Streptococcus Pneumoniae exhibited high neutrophil degranulation. Increased activity of the LXR-RXR pathway was associated with better survival.
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation which were associated with microbiology. Therapeutic targeting the LXR-XRX pathway with agonists may improve survival.
- Conditions
- Pleural Infection, Pleural Diseases, Pleural Effusion, Pleural Empyema, Pleural Infection Bacterial, Pleural Infections and Inflammations
- Keywords
- pleural, pleural infection, respiratory, neutrophils
- Medical subject headings
- Pleural Diseases, Pleural Effusion, Empyema, Pleural, Inflammation
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 |
|---|---|---|
| Enrolment | All samples were collect at patient enrolment for the PILOT study (PMID: 32675200, ISRCTN 50236700) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pleural infection endotypes
Discovery of pleural infection biological endotypes
Measured: 12 months
Association between endotypes and microbiology
Investigate the association between pleural infection endotypes and microbiology
Measured: 12 months
Association between endotypes and one-year survival
Investigate the association between pleural infection endotypes and one-year survival
Measured: 12 months
Secondary outcomes (2)
Association between endotypes and need for surgical treatment
Investigate the association between pleural infection endotypes and need for surgical treatment
Measured: 12 months
Association between levels of pleural fluid plasminogen and neutrophil elastase
Investigate the association between pleural fluid plasminogen and neutrophil elastase protein levels
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2024
- Study start20 Jun 2021
- Primary completion20 Jun 2023
- Study completion20 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pleural InfectionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06513689
- Sponsor's protocol ID
- R74885/RE001
- Acronym
- TORPIDS-2
- Status last verified
- Jun 2024
- First submitted
- 16 Jul 2024
- Last updated
- 22 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised and non-identifiable data could be shared with other researchers. The mass spectrometry data are deposited in PRIDE to share with other researchers.
Publications
"Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study." John P. Corcoran, Ioannis Psallidas, Stephen Gerry, Francesco Piccolo, Coenraad F. Koegelenberg, Tarek Saba, Cyrus Daneshvar, Ian Fairbairn, Richard Heinink, Alex West, Andrew E. Stanton, Jayne Holme, Jack A. Kastelik, Henry Steer, Nicola J. Downer, Mohammed Haris, Emma H. Baker, Caroline F. Everett, Justin Pepperell, Thomas Bewick, Lonny Yarmus, Fabien Maldonado, Burhan Khan, Alan Hart-Thomas, Georgina Hands, Geoffrey Warwick, Duneesha De Fonseka, Maged Hassan, Mohammed Munavvar, Anur Guhan, Mitra Shahidi, Zara Pogson, Lee Dowson, Natalia D. Popowicz, Judith Saba, Neil R. Ward, Rob J. Hallifax, Melissa Dobson, Rachel Shaw, Emma L. Hedley, Assunta Sabia, Barbara Robinson, Gary S. Collins, Helen E. Davies, Ly-Mee Yu, Robert F. Miller, Nick A. Maskell and Najib M. Rahman. Eur Respir J 2020; 56: 2000130. Eur Respir J. 2020 Dec 17;56(6):2050130. doi: 10.1183/13993003.50130-2020. Print 2020 Dec. No abstract available.
PubMed 33334780
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pleural Fluid Proteomics From Patients With Pleural Infection Shows Signatures of Diverse Neutrophilic Responses: The Oxford Pleural Infection Endotyping Study (TORPIDS 2)
- ClinicalTrials.gov ID
- NCT06513689
- Acronym / sponsor ID
- TORPIDS-2 / R74885/RE001
- Conditions
- Pleural Infection, Pleural Diseases, Pleural Effusion, Pleural Empyema, Pleural Infection Bacterial, Pleural Infections and Inflammations
- Keywords
- pleural, pleural infection, respiratory, neutrophils
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 20 Jun 2021 (actual)
- Primary completion
- 20 Jun 2023 (actual)
- Study completion
- 20 Jun 2024 (actual)
- First posted
- 22 Jul 2024 (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.
Pleural infection is a severe disease with increasing incidence worldwide. The subphenotypes of pleural infection remain unknown.We designed a study to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome.
We subjected 80 pleural fluid samples to unlabelled mass spectrometry.
Pathway analysis of the differentially expressed proteins identified the neutrophil degranulation, glycolysis, pentose phosphate pathway, and the liver and retinoid X receptors (LXR-RXR) activation. Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation.
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation.
Detailed description
Pleural infection is a common and severe disease with increasing incidence worldwide. The endotypes of pleural infection remain unknown. A better understanding of patient variation in underlying biological response to infection may lead to improved treatments and clinical outcomes. We designed a study with the aim to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome.
We subjected 80 pleural fluid samples from the PILOT study, a prospective study on pleural infection, to unlabelled mass spectrometry. Proteins were retained if they were detected in at least 50% of the samples resulting in a total of 449 proteins. Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples, Spearman and exact Fischer's methods were used for correlation assessment and protein expression was correlated with clinical outcomes.
UMAP plotting separated the samples in to two different and distinct cohorts. Pathway analysis of the differentially expressed proteins identified neutrophil degranulation, glycolysis, the pentose phosphate pathway, and the liver and retinoid X receptors (LXR-RXR) activation. Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation. Specimens dominated by Streptococcus Pneumoniae exhibited high neutrophil degranulation. Increased activity of the LXR-RXR pathway was associated with better survival.
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation which were associated with microbiology. Therapeutic targeting the LXR-XRX pathway with agonists may improve survival.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Enrolment | – | –All samples were collect at patient enrolment for the PILOT study (PMID: 32675200, ISRCTN 50236700) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with evidence of pleural infection
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
Pleural infection endotypes
Time frame: 12 months
Discovery of pleural infection biological endotypes
Association between endotypes and microbiology
Time frame: 12 months
Investigate the association between pleural infection endotypes and microbiology
Association between endotypes and one-year survival
Time frame: 12 months
Investigate the association between pleural infection endotypes and one-year survival
2 secondary outcomes
Association between endotypes and need for surgical treatment
Time frame: 12 months
Association between levels of pleural fluid plasminogen and neutrophil elastase
Time frame: 12 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 22 Jul 2024.
- Background: PubMed 33334780"Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study." John P. Corcoran, Ioannis Psallidas, Stephen Gerry, Francesco Piccolo, Coenraad F. Koegelenberg, Tarek Saba, Cyrus Daneshvar, Ian Fairbairn, Richard Heinink, Alex West, Andrew E. Stanton, Jayne Holme, Jack A. Kastelik, Henry Steer, Nicola J. Downer, Mohammed Haris, Emma H. Baker, Caroline F. Everett, Justin Pepperell, Thomas Bewick, Lonny Yarmus, Fabien Maldonado, Burhan Khan, Alan Hart-Thomas, Georgina Hands, Geoffrey Warwick, Duneesha De Fonseka, Maged Hassan, Mohammed Munavvar, Anur Guhan, Mitra Shahidi, Zara Pogson, Lee Dowson, Natalia D. Popowicz, Judith Saba, Neil R. Ward, Rob J. Hallifax, Melissa Dobson, Rachel Shaw, Emma L. Hedley, Assunta Sabia, Barbara Robinson, Gary S. Collins, Helen E. Davies, Ly-Mee Yu, Robert F. Miller, Nick A. Maskell and Najib M. Rahman. Eur Respir J 2020; 56: 2000130. Eur Respir J. 2020 Dec 17;56(6):2050130. doi: 10.1183/13993003.50130-2020. Print 2020 Dec. No abstract available.
- Individual participant dataSharing planned: Yes. Anonymised and non-identifiable data could be shared with other researchers. The mass spectrometry data are deposited in PRIDE to share with other researchers.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Pleural Infection and Pleural Diseases, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 22 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 United Kingdom. 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?
Pleural infection endotypes (time frame: 12 months). The study lists 3 primary outcomes in all. 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 NCT06513689, which also lists 1 linked publication.
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 22 Jul 2024.