Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing in ICU Patients.

Critical Illness Clinical Trial

Official title:

Detection of Pathogen and Antibiotic Resistance Genes by Targeted Next-Generation Sequencing Compared With Metagenomic Next-Generation Sequencing in ICU Patients.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06157372
• Other study ID #: SYSKY-2023-667-03
• Status: Not yet recruiting
• Start date: December 20, 2023
• Est. completion date: August 10, 2024

Study information

• Verified date: November 2023
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: Ting Li
• Phone: 011-86-15608657562
• Email: 3423580562[@]qq.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: August 10, 2024
• Est. primary completion date: August 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Critical Illness
• Diagnosis
• Infections

Intervention

Diagnostic Test:
• targeted next-generation sequencing (tNGS)
To provide rapid etiological diagnosis of patients by means of targeted next-generation sequencing.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

References & Publications (6)

Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019 Jun;20(6):341-355. doi: 10.1038/s41576-019-0113-7. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 year
Primary	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.	1 year
Secondary	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.	1 year
Secondary	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.	1 year
Secondary	Positive predictive value	Positive predictive value is the probability that subjects with a positive test truly have the disease.	1 year
Secondary	Negative predictive value	Negative predictive value is the probability that subjects with a negative screening test truly don't have the disease.	1 year
Secondary	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.	1 year
Secondary	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.	1 year