Urinary Tract InfectionsPGS-U-UTI&UCNCT05624476
mNGS for Therapy of Urinary Infectious Diseases
An observational study of Urinary Tract Infections and Sequelae of; Infection, run by Shanghai Changzheng Hospital.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Urinary Tract Infections, Sequelae of; Infection
- What is being tested?
- mNGS of urine cell-free DNA
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2023to 31 Dec 2023
- 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 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Urinary Tract Infections, Sequelae of; Infection
- Being tested
- mNGS of urine cell-free DNA
- Medical subject headings
- Urinary Tract Infections, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mNGS of urine cell-free DNADiagnostic test
Metagenomic sequencing of urine cell-free DNA
| Study group | Role | What they receive |
|---|---|---|
| experimental group | Patients with urinary tract infection received treatments guided by both culture and mNGS Receives: Diagnostic Test: mNGS of urine cell-free DNA | |
| control group | Patients with urinary tract infection received treatments guided by culture first Receives: Diagnostic Test: mNGS of urine cell-free DNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants cured from urinary tract infection
The "cure" is defined as "The clinical symptom of urinary tract infection disappeared and the urine tests returned to normal"
Measured: 17 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2022
- Study start1 Jan 2023 (estimated)
- Primary completion30 Sep 2023 (estimated)
- Study completion31 Dec 2023 (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 Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by Shanghai Changzheng HospitalThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Junxue Wang, Prof., Principal investigator, Changzheng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05624476
- Sponsor's protocol ID
- CZGR2022002
- Acronym
- PGS-U-UTI&UC
- Status last verified
- Nov 2022
- First submitted
- 14 Nov 2022
- Last updated
- 22 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015 May;13(5):269-84. doi: 10.1038/nrmicro3432. Epub 2015 Apr 8.
PubMed 25853778Frimodt-Moller N. The urine microbiome - Contamination or a novel paradigm? EBioMedicine. 2019 Jun;44:20-21. doi: 10.1016/j.ebiom.2019.05.016. Epub 2019 May 14. No abstract available.
PubMed 31101594Janes VA, Matamoros S, Munk P, Clausen PTLC, Koekkoek SM, Koster LAM, Jakobs ME, de Wever B, Visser CE, Aarestrup FM, Lund O, de Jong MD, Bossuyt PMM, Mende DR, Schultsz C. Metagenomic DNA sequencing for semi-quantitative pathogen detection from urine: a prospective, laboratory-based, proof-of-concept study. Lancet Microbe. 2022 Aug;3(8):e588-e597. doi: 10.1016/S2666-5247(22)00088-X. Epub 2022 Jun 7.
PubMed 35688170Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014 Mar;28(1):1-13. doi: 10.1016/j.idc.2013.09.003. Epub 2013 Dec 8.
PubMed 24484571Mitchell SL, Simner PJ. Next-Generation Sequencing in Clinical Microbiology: Are We There Yet? Clin Lab Med. 2019 Sep;39(3):405-418. doi: 10.1016/j.cll.2019.05.003.
PubMed 31383265Zeng S, Ying Y, Xing N, Wang B, Qian Z, Zhou Z, Zhang Z, Xu W, Wang H, Dai L, Gao L, Zhou T, Ji J, Xu C. Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA. Clin Cancer Res. 2020 Nov 1;26(21):5646-5654. doi: 10.1158/1078-0432.CCR-20-0401. Epub 2020 Oct 9.
PubMed 33037018
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pan-genome Sequencing of Urine Cell-free DNA for Therapy of Urinary Infectious Diseases: a Single Center Prospective Study Clinical Control Study
- ClinicalTrials.gov ID
- NCT05624476
- Acronym / sponsor ID
- PGS-U-UTI&UC / CZGR2022002
- Conditions
- Urinary Tract Infections, Sequelae of; Infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 22 Nov 2022 (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.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| experimental group | – | Diagnostic Test: mNGS of urine cell-free DNAPatients with urinary tract infection received treatments guided by both culture and mNGS |
| control group | – | Diagnostic Test: mNGS of urine cell-free DNAPatients with urinary tract infection received treatments guided by culture first |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
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 |
|---|---|---|
| mNGS of urine cell-free DNAMetagenomic sequencing of urine cell-free DNA | Diagnostic test | control group, experimental group |
Primary outcome
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"
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2022.
- Results publication: PubMed 25853778Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015 May;13(5):269-84. doi: 10.1038/nrmicro3432. Epub 2015 Apr 8.
- Results publication: PubMed 31101594Frimodt-Moller N. The urine microbiome - Contamination or a novel paradigm? EBioMedicine. 2019 Jun;44:20-21. doi: 10.1016/j.ebiom.2019.05.016. Epub 2019 May 14. No abstract available.
- Results publication: PubMed 35688170Janes VA, Matamoros S, Munk P, Clausen PTLC, Koekkoek SM, Koster LAM, Jakobs ME, de Wever B, Visser CE, Aarestrup FM, Lund O, de Jong MD, Bossuyt PMM, Mende DR, Schultsz C. Metagenomic DNA sequencing for semi-quantitative pathogen detection from urine: a prospective, laboratory-based, proof-of-concept study. Lancet Microbe. 2022 Aug;3(8):e588-e597. doi: 10.1016/S2666-5247(22)00088-X. Epub 2022 Jun 7.
- Results publication: PubMed 24484571Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014 Mar;28(1):1-13. doi: 10.1016/j.idc.2013.09.003. Epub 2013 Dec 8.
- Results publication: PubMed 31383265Mitchell SL, Simner PJ. Next-Generation Sequencing in Clinical Microbiology: Are We There Yet? Clin Lab Med. 2019 Sep;39(3):405-418. doi: 10.1016/j.cll.2019.05.003.
- Results publication: PubMed 33037018Zeng S, Ying Y, Xing N, Wang B, Qian Z, Zhou Z, Zhang Z, Xu W, Wang H, Dai L, Gao L, Zhou T, Ji J, Xu C. Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA. Clin Cancer Res. 2020 Nov 1;26(21):5646-5654. doi: 10.1158/1078-0432.CCR-20-0401. Epub 2020 Oct 9.
- 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.
Junxue Wang, Prof. principal investigator
Changzheng Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Urinary Tract Infections and Sequelae of; Infection, run by Shanghai Changzheng Hospital.
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 4 inclusion and 10 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 22 Nov 2022. 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 Xiaofeng Hang, Prof. (+8613516063666, hangxfdoc@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants cured from urinary tract infection (time frame: 17 days). 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 NCT05624476, 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 22 Nov 2022.