UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000049276 |
|---|---|
| Receipt number | R000056117 |
| Scientific Title | Next-generation sequencing to predict phenotypic drug sensitivity of tuberculosis: meta-analysis of diagnostic test accuracy |
| Date of disclosure of the study information | 2022/10/20 |
| Last modified on | 2024/04/03 14:10:41 |
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Basic information
Public title
Next-generation sequencing to predict phenotypic drug sensitivity of tuberculosis: meta-analysis of diagnostic test accuracy
Acronym
Next-generation sequencing to predict phenotypic drug sensitivity of tuberculosis: meta-analysis of diagnostic test accuracy
Scientific Title
Next-generation sequencing to predict phenotypic drug sensitivity of tuberculosis: meta-analysis of diagnostic test accuracy
Scientific Title:Acronym
Next-generation sequencing to predict phenotypic drug sensitivity of tuberculosis: meta-analysis of diagnostic test accuracy
Region
| Japan |
Condition
Condition
M. tuberculosis infection
Classification by specialty
| Infectious disease |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
Conventionally, phenotypic antimicrobial susceptibility has been evaluated using culture media with antimicrobial agent. However, this may take weeks to obtain the test results. Instead, real-time PCR based genetic tests such as GeneXpert have been commercially available and widely used. Since the last decade, "next-generation" sequencing has become less costly and readily available for daily clinical setting. Whole-genome sequencing (WGS), a type of next-generation sequencings, can determine the whole allay of nucleotides and assess multiple genes simultaneously. Some systematic reviews mentioned specific genes that determine drug susceptibility. However, most clinicians need to know the phenotypic antimicrobial susceptibility instead of genetic information. Phenotypic drug sensitivity test (pDST) results of M. tuberculosis directly guide anti-tuberculosis regimen selection. Many previous studies reported inconsistent result how WGS can predict pDST. Therefore, systematic review and meta-analysis of diagnostic test accuracy is anticipated to summarize data of this topic. To our knowledge, one systematic review pooled diagnostic test accuracy of WGS for isoniazid and rifampicin resistance. However, meta-analysis for other key drugs have not been published. This study aimed to demonstrate diagnostic test accuracy of WGS to predict pDST for each of anti-tuberculosis drugs.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
Drugs of our interests are isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, amikacin, kanamycin, para-amino-salicylic acid (PAS), capreomycin, levofloxacin, moxifloxacin, ofloxacin, ethionamide, protionamide, and cyclocerine. Combined evaluation of quinolones, first-line drugs, and second-line drugs will not be adopted. Diagnostic odds ratio (DOR), area under the curve (AUC) of summary receiver operating characteristics curve (SROC), estimated sensitivity, and specificity will be calculated.
Key secondary outcomes
Base
Study type
Others,meta-analysis etc
Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| Not applicable |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
English-language articles that provide data for both sensitivity and specificity of WGS to predict pDST will be included. Sequencing method should be clearly declared as WGS in the article. Conference abstract will be excluded. Data regarding sensitivity and specificity should be clearly presented. A number of isolates should be larger than 20. To avoid duplicate use of the same database, research conducted as consortium and a study using public WGS data repository will be excluded.
M. tuberculosis culture isolate and other clinical samples are accepted. All samples should have underwent pDST.
Key exclusion criteria
A number of isolates should be larger than 20.
Target sample size
Research contact person
Name of lead principal investigator
| 1st name | Nobuyuki |
| Middle name | |
| Last name | Horita |
Organization
Yokohama City University Hospital
Division name
Chemotherapy Center
Zip code
236-0004
Address
3-9, Fukuura, Kanazawa, Yokohama, Japan
TEL
045-787-2800
horitano@yokohama-cu.ac.jp
Public contact
Name of contact person
| 1st name | Nobuyuki |
| Middle name | |
| Last name | Horita |
Organization
Yokohama City University Hospital
Division name
Chemotherapy Center
Zip code
236-0004
Address
3-9, Fukuura, Kanazawa, Yokohama, Japan
TEL
045-787-2800
Homepage URL
horitano@yokohama-cu.ac.jp
Sponsor or person
Institute
Yokohama City University Hospital, Chemotherapy Center
Institute
Department
Personal name
Funding Source
Organization
Yokohama City University Hospital, Chemotherapy Center
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Yokohama City University Hospital
Address
3-9, Fukuura, Kanazawa, Yokohama, Japan
Tel
045-787-2800
horitano@yokohama-cu.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2022 | Year | 10 | Month | 20 | Day |
Related information
URL releasing protocol
https://pubmed.ncbi.nlm.nih.gov/37946558/
Publication of results
Unpublished
Result
URL related to results and publications
https://pubmed.ncbi.nlm.nih.gov/37946558/
Number of participants that the trial has enrolled
16821
Results
See below:
Yoichi Tagami, Nobuyuki Horita, Megumi Kaneko et al. J Infect Dis. 2023 Nov 8:jiad480. Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis
Results date posted
| 2024 | Year | 04 | Month | 03 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
See below:
Yoichi Tagami, Nobuyuki Horita, Megumi Kaneko et al. J Infect Dis. 2023 Nov 8:jiad480. Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis
Participant flow
See below:
Yoichi Tagami, Nobuyuki Horita, Megumi Kaneko et al. J Infect Dis. 2023 Nov 8:jiad480. Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis
Adverse events
See below:
Yoichi Tagami, Nobuyuki Horita, Megumi Kaneko et al. J Infect Dis. 2023 Nov 8:jiad480. Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis
Outcome measures
See below:
Yoichi Tagami, Nobuyuki Horita, Megumi Kaneko et al. J Infect Dis. 2023 Nov 8:jiad480. Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Main results already published
Date of protocol fixation
| 2020 | Year | 10 | Month | 20 | Day |
Date of IRB
| 2020 | Year | 10 | Month | 20 | Day |
Anticipated trial start date
| 2020 | Year | 10 | Month | 20 | Day |
Last follow-up date
| 2021 | Year | 12 | Month | 31 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
The following search formula will be used for Web of Science: TS=((whole genome sequencing OR WGS OR genomic) AND (TB OR PTB or tuberculosis OR MTC OR mycobacterium) AND (sensitivity OR specificity OR predictive value OR likelihood OR receiver operating OR ROC OR area under curve OR AUC) AND (resistant OR resistance OR susceptible OR susceptibility OR phenotype OR phenotypic)). PubMed, Cochrane Central, EMBASE, and Allied & Complementary Medicine will also be searched using similar formulas. The date of electrical database searching is October 21, 2022.
Two review authors (YT and NH) will independently judge eligibility of candidate articles. They will discuss and resolve the discordance.
Phenotypic drug sensitivity/susceptibility test (pDST) and phenotypic antimicrobial sensitivity/susceptibility test are used as a reference test.
WGS to predict drug sensitivity is considered as the index tests. WGS results may be judged based on mutations of multiple genes.
A bivariate model was applied to obtain SROC. The DerSimonian-Laird random model will be used for DOR. We will run "mada" package of R project (Gerta Rucker, Denmark). We will draw paired forest plots using RevMan version 5.4.1 (Cochrane, London, UK).
Management information
Registered date
| 2022 | Year | 10 | Month | 20 | Day |
Last modified on
| 2024 | Year | 04 | Month | 03 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000056117
