InfectionsNCT06157372
Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing in ICU Patients.
An observational study of Infections and Critical Illness, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.
Trial summary
It is difficult to determine the pathogens in the early stage of infection in critically ill patients, and empirical use of broad-spectrum antibiotics for a long time is often necessary, leading to antibiotics drug resistance. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Infections, Critical Illness, Diagnosis
- What is being tested?
- targeted next-generation sequencing (tNGS)
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 20 Dec 2023to 10 Aug 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients in ICU truly have infected disease and non-infected disease diagnosed by two ICU physicians determining whether the patient have an infectious etiology and identifying the pathogen through existing clinical guidelines, clinical features, laboratory tests, microbiological tests, chest imaging, and treatment response.
Who may be able to join
- The presence of an infection or clearly excluded the presence of infection.
- Etiological culture and/or metagenomic next-generation sequencing detection of specimens sent for testing.
Who cannot join
- Suspected infection.
- Participation in other clinical trials in the past 2 months.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing Compared With Metagenomic Next-Generation Sequencing in ICU Patients.
It is difficult to determine the pathogens in the early stage of infection in critically ill patients, and empirical use of broad-spectrum antibiotics for a long time is often necessary, leading to antibiotics drug resistance. Targeted next generation sequencing (tNGS) can provide faster results for pathogen and related antibiotic resistant diagnosis. But it lacks sufficient clinical evidence. Evidence regarding the clinical diagnostic accuracy and drug resistance is needed to comprehensively evaluate targeted next generation sequencing (tNGS) for diagnosis of patients in ICU who and will be critical to inform national policy.
Read the detailed description
Infectious diseases are one of the highest mortality and morbidity diseases in humans. Due to the difficulty in identifying the pathogen in the early stage of infection, patients with severe infections often need to empirically use broad-spectrum antimicrobials for a long time. The traditional gold standard of etiological detection - etiological culture, even in sepsis patients, only about 60% of the results are positive. Therefore, the accurate identification and rapid classification of pathogenic microorganisms is very important for the patient's precise diagnosis and timely treatment.
Metagenomic next generation sequencing (mNGS), which has emerged in recent years, have been shown to provide early diagnosis and targeted medication guidance for bloodstream infections and respiratory infections, but it is expensive and not able to provide related drug resistant genes. Therefore, targeted next generation sequencing (tNGS) has been derived, which is characterized by rapid sequencing and genetic testing for drug resistance.
The purpose of this study is to evaluate the efficacy of etiological diagnosis and provide patients with more accurate treatment.
- Conditions
- Infections, Critical Illness, Diagnosis
- Being tested
- targeted next-generation sequencing (tNGS)
- Keywords
- Targeted Next-generation sequencing, ICU, infections, Next-generation sequencing
- Medical subject headings
- Infections, Critical Illness, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
targeted next-generation sequencing (tNGS)Diagnostic test
To provide rapid etiological diagnosis of patients by means of targeted next-generation sequencing.
| Study group | Role | What they receive |
|---|---|---|
| Non-Infection group | Participants received traditional etiological culture of suspected site of infection. Receives: Diagnostic Test: targeted next-generation sequencing (tNGS) | |
| Infection group | Participants received traditional etiological culture, metagenomic next-generation sequencing of infectious sites. Receives: Diagnostic Test: targeted next-generation sequencing (tNGS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity
The probability of being positive in clinical composite diagnosis, the probability that etiological culture, mNGS, and tNGS tests are also positive, which is also known as the true positive rate.
Measured: 1 year
Specificity
It refers to the probability that cultures, mNGS, and tNGS tests are also negative in the presence of non-infection confirmed by the gold standard.
Measured: 1 year
Secondary outcomes (6)
False-positive rate
It refers to the probability that the gold-standard confirmed absence of infection is also positive for etiological culture, mNGS, and tNGS tests.
Measured: 1 year
False-negative rate
It refers to the probability of being positive in the clinical composite diagnosis, and the probability that etiological cultures, mNGS, and tNGS tests will also be negative.
Measured: 1 year
Positive predictive value
Positive predictive value is the probability that subjects with a positive test truly have the disease.
Measured: 1 year
Negative predictive value
Negative predictive value is the probability that subjects with a negative screening test truly don't have the disease.
Measured: 1 year
Kappa values
Kappa values are used to measure the agreement between two raters. The range of possible values of kappa is from -1 to 1, though it usually falls between 0 and 1. Unity represents perfect agreement, indicating that the raters agree in their classification of every case. Kappa values of 0.41~0.60 are moderately consistent, 0.61~0.80 are basically consistent, and 0.81~1.00 is almost identical.
Measured: 1 year
Drug resistant gene by targeted next-generation sequencing
It refers to the distribution of drug resistance by targeted next-generation sequencing using the Comprehensive Antibiotic Resistance Database.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2023
- Study start20 Dec 2023 (estimated)
- Primary completion10 Aug 2024 (estimated)
- Study completion10 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for InfectionsStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityThe 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
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhijie He, Study director, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06157372
- Sponsor's protocol ID
- SYSKY-2023-667-03
- Status last verified
- Nov 2023
- First submitted
- 19 Oct 2023
- Last updated
- 5 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019 Jun;20(6):341-355. doi: 10.1038/s41576-019-0113-7.
PubMed 30918369Diao Z, Han D, Zhang R, Li J. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections. J Adv Res. 2021 Sep 29;38:201-212. doi: 10.1016/j.jare.2021.09.012. eCollection 2022 May.
PubMed 35572406Miao Q, Ma Y, Wang Q, Pan J, Zhang Y, Jin W, Yao Y, Su Y, Huang Y, Wang M, Li B, Li H, Zhou C, Li C, Ye M, Xu X, Li Y, Hu B. Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S231-S240. doi: 10.1093/cid/ciy693.
PubMed 30423048Pei XM, Yeung MHY, Wong ANN, Tsang HF, Yu ACS, Yim AKY, Wong SCC. Targeted Sequencing Approach and Its Clinical Applications for the Molecular Diagnosis of Human Diseases. Cells. 2023 Feb 2;12(3):493. doi: 10.3390/cells12030493.
PubMed 36766834Li S, Tong J, Liu Y, Shen W, Hu P. Targeted next generation sequencing is comparable with metagenomic next generation sequencing in adults with pneumonia for pathogenic microorganism detection. J Infect. 2022 Nov;85(5):e127-e129. doi: 10.1016/j.jinf.2022.08.022. Epub 2022 Aug 26. No abstract available.
PubMed 36031154Gaston DC, Miller HB, Fissel JA, Jacobs E, Gough E, Wu J, Klein EY, Carroll KC, Simner PJ. Evaluation of Metagenomic and Targeted Next-Generation Sequencing Workflows for Detection of Respiratory Pathogens from Bronchoalveolar Lavage Fluid Specimens. J Clin Microbiol. 2022 Jul 20;60(7):e0052622. doi: 10.1128/jcm.00526-22. Epub 2022 Jun 13.
PubMed 35695488
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing Compared With Metagenomic Next-Generation Sequencing in ICU Patients.
- ClinicalTrials.gov ID
- NCT06157372
- Acronym / sponsor ID
- SYSKY-2023-667-03
- Conditions
- Infections, Critical Illness, Diagnosis
- Keywords
- Targeted Next-generation sequencing, ICU, infections, Next-generation sequencing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 20 Dec 2023 (estimated)
- Primary completion
- 10 Aug 2024 (estimated)
- Study completion
- 10 Aug 2024 (estimated)
- First posted
- 5 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.
It is difficult to determine the pathogens in the early stage of infection in critically ill patients, and empirical use of broad-spectrum antibiotics for a long time is often necessary, leading to antibiotics drug resistance. Targeted next generation sequencing (tNGS) can provide faster results for pathogen and related antibiotic resistant diagnosis. But it lacks sufficient clinical evidence. Evidence regarding the clinical diagnostic accuracy and drug resistance is needed to comprehensively evaluate targeted next generation sequencing (tNGS) for diagnosis of patients in ICU who and will be critical to inform national policy.
Detailed description
Infectious diseases are one of the highest mortality and morbidity diseases in humans. Due to the difficulty in identifying the pathogen in the early stage of infection, patients with severe infections often need to empirically use broad-spectrum antimicrobials for a long time. The traditional gold standard of etiological detection - etiological culture, even in sepsis patients, only about 60% of the results are positive. Therefore, the accurate identification and rapid classification of pathogenic microorganisms is very important for the patient's precise diagnosis and timely treatment.
Metagenomic next generation sequencing (mNGS), which has emerged in recent years, have been shown to provide early diagnosis and targeted medication guidance for bloodstream infections and respiratory infections, but it is expensive and not able to provide related drug resistant genes. Therefore, targeted next generation sequencing (tNGS) has been derived, which is characterized by rapid sequencing and genetic testing for drug resistance.
The purpose of this study is to evaluate the efficacy of etiological diagnosis and provide patients with more accurate treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-Infection group | – | Diagnostic Test: targeted next-generation sequencing (tNGS)Participants received traditional etiological culture of suspected site of infection. |
| Infection group | – | Diagnostic Test: targeted next-generation sequencing (tNGS)Participants received traditional etiological culture, metagenomic next-generation sequencing of infectious sites. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients in ICU truly have infected disease and non-infected disease diagnosed by two ICU physicians determining whether the patient have an infectious etiology and identifying the pathogen through existing clinical guidelines, clinical features, laboratory tests, microbiological tests, chest imaging, and treatment response.
Key inclusion criteria (2 listed)
- The presence of an infection or clearly excluded the presence of infection.
- Etiological culture and/or metagenomic next-generation sequencing detection of specimens sent for testing.
Key exclusion criteria (2 listed)
- Suspected infection.
- Participation in other clinical trials in the past 2 months.
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 |
|---|---|---|
| targeted next-generation sequencing (tNGS)To provide rapid etiological diagnosis of patients by means of targeted next-generation sequencing. | Diagnostic test | Infection group, Non-Infection group |
Primary outcome
Sensitivity
Time frame: 1 year
The probability of being positive in clinical composite diagnosis, the probability that etiological culture, mNGS, and tNGS tests are also positive, which is also known as the true positive rate.
Specificity
Time frame: 1 year
It refers to the probability that cultures, mNGS, and tNGS tests are also negative in the presence of non-infection confirmed by the gold standard.
6 secondary outcomes
False-positive rate
Time frame: 1 year
False-negative rate
Time frame: 1 year
Positive predictive value
Time frame: 1 year
Negative predictive value
Time frame: 1 year
Kappa values
Time frame: 1 year
Drug resistant gene by targeted next-generation sequencing
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
- Background: PubMed 30918369Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019 Jun;20(6):341-355. doi: 10.1038/s41576-019-0113-7.
- Background: PubMed 35572406Diao Z, Han D, Zhang R, Li J. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections. J Adv Res. 2021 Sep 29;38:201-212. doi: 10.1016/j.jare.2021.09.012. eCollection 2022 May.
- Background: PubMed 30423048Miao Q, Ma Y, Wang Q, Pan J, Zhang Y, Jin W, Yao Y, Su Y, Huang Y, Wang M, Li B, Li H, Zhou C, Li C, Ye M, Xu X, Li Y, Hu B. Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S231-S240. doi: 10.1093/cid/ciy693.
- Background: PubMed 36766834Pei XM, Yeung MHY, Wong ANN, Tsang HF, Yu ACS, Yim AKY, Wong SCC. Targeted Sequencing Approach and Its Clinical Applications for the Molecular Diagnosis of Human Diseases. Cells. 2023 Feb 2;12(3):493. doi: 10.3390/cells12030493.
- Background: PubMed 36031154Li S, Tong J, Liu Y, Shen W, Hu P. Targeted next generation sequencing is comparable with metagenomic next generation sequencing in adults with pneumonia for pathogenic microorganism detection. J Infect. 2022 Nov;85(5):e127-e129. doi: 10.1016/j.jinf.2022.08.022. Epub 2022 Aug 26. No abstract available.
- Background: PubMed 35695488Gaston DC, Miller HB, Fissel JA, Jacobs E, Gough E, Wu J, Klein EY, Carroll KC, Simner PJ. Evaluation of Metagenomic and Targeted Next-Generation Sequencing Workflows for Detection of Respiratory Pathogens from Bronchoalveolar Lavage Fluid Specimens. J Clin Microbiol. 2022 Jul 20;60(7):e0052622. doi: 10.1128/jcm.00526-22. Epub 2022 Jun 13.
- 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.
Zhijie He study director
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Questions about this trial
What is this clinical trial studying?
An observational study of Infections and Critical Illness, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.
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 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 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
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 Ting Li (011-86-15608657562, 3423580562@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity (time frame: 1 year). The study lists 2 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 NCT06157372, which also lists 6 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 5 Dec 2023.