mNGS for Therapy of Urinary Infectious Diseases (PGS-U-UTI&UC)

November 20, 2022 updated by: Shanghai Changzheng Hospital

Pan-genome Sequencing of Urine Cell-free DNA for Therapy of Urinary Infectious Diseases: a Single Center Prospective Study Clinical Control Study

Urinary tract infection is a common infectious disease in clinic. Although urinary tract infection can be initially diagnosed by clinical sign and symptom, signs and urine routine, the application of appropriate antibiotic therapy depends on the further identification of pathogens.

Metagenomic sequencing has been widely used in clinical pathogen diagnosis, especially in difficult infectious diseases. ICompared with tissue samples, cerebrospinal fluid, bronchoalveolar lavage fluid, whole blood and other samples, the application of mNGS in urine samples is relatively limited because incorrect sampling methods before and after collection of urine samples are easy to contaminate the samples and the colonization of distal urethra, periurethral skin and vagina will interfere with the interpretation of reports.

Previous small sample studies have shown that the sensitivity of mNGS in urinary tract infection is high, but the specificity is relatively low, and there are many problems such as difficult interpretation of reports and low clinical conformity. This is closely related to the mNGS technology algorithm, such as the inability to eliminate the influence of urinary system background bacteria, and the ambiguity of short sequence alignment, which makes it difficult to distinguish homologous pathogens.

In this study, based on the standard mNGS sequencing process, the improved Z value analysis method was used to select strictly enrolled clinical samples and compare them with pathogen culture to observe the clinical value of mNGS with Z value analysis method in the treatment of urinary tract infection.

Study Overview

Status

Not yet recruiting

Detailed Description

Urinary tract infection is a common infectious disease in clinic. Urinary tract infection is easily caused by abnormal structure and function of urinary system, low immunity, pregnancy, gender and sexual activity, and iatrogenic factors. Urinary tract infection has a wide spectrum of pathogenic microorganisms, including Gram-negative bacilli, Gram-positive cocci, fungi, mycoplasma, chlamydia, viruses and so on. Although urinary tract infection can be initially diagnosed by clinical sign and symptom, signs and urine routine, the application of appropriate antibiotic therapy depends on the further identification of pathogens. At present, it is commonly used to collect midstream urine for pathogen culture in clinic, but it has the disadvantages of time-consuming and low detection rate, and the use of antibiotics can affect the results of culture.

Metagenomic sequencing has been widely used in clinical pathogen diagnosis, especially in difficult infectious diseases. Its principle is to collect samples, use mNGS to process the samples before sequencing, expose the nucleic acid, compare the nucleic acid sequence of pathogens with the designated huge biological database, and realize the comprehensive detection of viruses, bacteria, fungi, parasites and atypical microorganisms. Compared with tissue samples, cerebrospinal fluid, bronchoalveolar lavage fluid, whole blood and other samples, the application of mNGS in urine samples is relatively limited because incorrect sampling methods before and after collection of urine samples are easy to contaminate the samples and the colonization of distal urethra, periurethral skin and vagina will interfere with the interpretation of reports. However, mNGS has obvious advantages in clinical diagnosis, with high specificity and accuracy, and shorter detection time than traditional culture. In the aspect of mixed infection, because of its non-bias, the detection rate of multiple pathogens is higher than that of conventional culture, smear, PCR and other tests, which can detect other pathogens and even rare pathogens that can not be detected conventionally.

Previous small sample studies have shown that the sensitivity of mNGS in urinary tract infection is high, but the specificity is relatively low, and there are many problems such as difficult interpretation of reports and low clinical conformity. For example, there are many pathogens with high reading, and the test results are sorted to form a list of pathogens, but it is impossible to determine which or which pathogens are pathogenic. This is closely related to the mNGS technology algorithm, such as the inability to eliminate the influence of urinary system background bacteria, and the ambiguity of short sequence alignment, which makes it difficult to distinguish homologous pathogens.

In this study, based on the standard mNGS sequencing process, the improved Z value analysis method was used to select strictly enrolled clinical samples and compare them with pathogen culture to observe the clinical value of mNGS with Z value analysis method in the treatment of urinary tract infection.

Study Type

Observational

Enrollment (Anticipated)

72

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 68 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with urinary tract infection, which is caused by abnormal structure and function of urinary system, low immunity, pregnancy, gender and sexual activity, and iatrogenic factors, with a wide spectrum of pathogenic microorganisms, including Gram-negative bacilli, Gram-positive cocci, fungi, mycoplasma, chlamydia, viruses and so on, and diagnosed by clinical sign and symptom, signs and urine routine.

Description

Inclusion Criteria:

  • Age: 16-70 years.
  • Typical symptoms of urinary tract infection + pyuria (WBC ≥ 10/HP in urine sediment after centrifugation).
  • Clinical diagnosis: acute cystitis, urethritis, acute and chronic prostatitis, pyelonephritis, epididymitis; or complex urinary tract infection, such as urinary tract deformity, obstruction, double J tube, etc.
  • Sign the informed consent form voluntarily.

Exclusion Criteria:

  • Malignant tumors of liver or other organs or previous history of tumors.
  • Complicated with gastrointestinal bleeding, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome and acute infection.
  • Patients with severe heart, lung, kidney or blood system diseases and failure.
  • Pregnant or breastfeeding women.
  • Allergic constitution.
  • Those who have a history of alcoholism and drug abuse and fail to give up effectively.
  • The subject withdrew from the study on the condition that he/she had not participated in other clinical trials within 4 weeks.
  • Other conditions which, in the opinion of the investigator, are not suitable for participation in the study.
  • Antibiotic therapy was performed in the past month because of urinary tract infection.
  • Broad-spectrum antibiotic therapy has been performed for other uncontrollable infections or other infections.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
experimental group
Patients with urinary tract infection received treatments guided by both culture and mNGS
Metagenomic sequencing of urine cell-free DNA
control group
Patients with urinary tract infection received treatments guided by culture first
Metagenomic sequencing of urine cell-free DNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants cured from urinary tract infection
Time Frame: 17 days
The "cure" is defined as "The clinical symptom of urinary tract infection disappeared and the urine tests returned to normal"
17 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Junxue Wang, Prof., Changzheng hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2023

Primary Completion (Anticipated)

September 30, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

November 14, 2022

First Submitted That Met QC Criteria

November 20, 2022

First Posted (Actual)

November 22, 2022

Study Record Updates

Last Update Posted (Actual)

November 22, 2022

Last Update Submitted That Met QC Criteria

November 20, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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