Clinical trial NCT06157372: Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing in ICU Patients.
Official title: Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing Compared With Metagenomic Next-Generation Sequencing in ICU Patients.
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Infections
Critical Illness
Diagnosis
Keywords: Targeted Next-generation sequencing
ICU
infections
Next-generation sequencing
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2023-12-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Suspected infection.
* Participation in other clinical trials in the past 2 months.

Primary outcomes:
measure: Sensitivity
timeFrame: 1 year
measure: Specificity
timeFrame: 1 year
Secondary outcomes:
measure: False-positive rate
timeFrame: 1 year
measure: False-negative rate
timeFrame: 1 year
measure: Positive predictive value
timeFrame: 1 year
measure: Negative predictive value
timeFrame: 1 year
measure: Kappa values
timeFrame: 1 year
measure: Drug resistant gene by targeted next-generation sequencing
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Zhijie He
role: STUDY_DIRECTOR
References:
citation: Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019 Jun;20(6):341-355. doi: 10.1038/s41576-019-0113-7.
citation: Diao 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.
citation: Miao 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.
citation: Pei 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.
citation: Li 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.
citation: Gaston 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.