Xpert MTB/XDR Clinical Evaluation Trial
Multicentre Clinical Trial to Assess the Performance of the Xpert MTB/XDR Assay for INH- and Second-line Resistance Detection
1 other identifier
observational
710
1 country
1
Brief Summary
FIND and partners intend to address the need for a multi- and extensively drug-resistant tuberculosis (M/XDR-TB) diagnostic solution for patients in settings with a high burden of drug-resistant tuberculosis (DR-TB) though the development, evaluation and introduction of an Xpert MTB/XDR assay
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Jul 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 5, 2018
CompletedFirst Posted
Study publicly available on registry
November 2, 2018
CompletedStudy Start
First participant enrolled
July 11, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 18, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 18, 2020
CompletedMay 19, 2021
April 1, 2020
1.1 years
October 5, 2018
May 17, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
Estimate the diagnostic accuracy of the Xpert MTB/XDR assay for INH and ETH resistance detection
Sensitivity and specificity estimates for INH and ETH resistance detection
Day 1
Estimate the diagnostic accuracy of the Xpert MTB/XDR assay for fluoroquinolone resistance detection
Sensitivity and specificity estimates for fluoroquinolone resistance detection
Day 1
Estimate the diagnostic accuracy of the Xpert MTB/XDR assay for second-line injectable resistance detection
Sensitivity and specificity estimates for second-line injectable resistance detection
Day 1
Study Arms (2)
TB case detection Group
Patients with pulmonary TB symptoms and at least one DR-TB risk factor will be screened by Xpert MTB/RIF or Ultra. Patients with a clear TB-positive and RIF-resistant or RIF-sensitive result by Xpert MTB/RIF or Ultra and who consent to study procedures will be tested by Xpert MTB/XDR.
RIF-resistance MTB Group
An anticipated 316 additional RIF-resistant patients, as detected by Xpert MTB. /RIF, will be enrolled in this study to evaluate sensitivity and specificity of the Xpert MTB/XDR test against strains with other potential drug-resistance mutations.
Interventions
The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) is an integrated, automated, cartridge-based system for MDR-TB diagnosis that uses the GeneXpert instrument platform. WHO confirmed evidence to support the widespread use of the Xpert MTB/RIF assay in 2010 and the assay has since been widely used in TB programs, but it is only capable of identifying Mycobacterium tuberculosis (Mtb) and detecting RIF resistance. The Xpert MTB/XDR assay will be evaluated for INH and second-line resistance detection, and to recommend its use in diverse clinical settings. The focus of this protocol is the multicentre clinical evaluation.
Eligibility Criteria
Individuals who have one or more risk factors for DR-TB presenting to participating centres will be screened by Xpert MTB/RIF or Ultra. Those who test MTB-positive by Xpert MTB/RIF or Ultra at the study sites will be asked to participate. Individuals will be recruited at outpatient clinic settings and inpatient hospital settings. HIV-positive individuals and HIV-negative individuals will be included in this study.
You may qualify if:
- Age 18 years or above;
- Symptoms suggesting pulmonary TB, i.e. persistent cough (generally ≥3 weeks or as per local definition of TB suspect), and at least one of the following:
- Previously received \>1 month of treatment for a prior TB episode or
- Failing TB treatment with positive sputum smear or culture after ≥3 months of a standard TB treatment or
- Had close contact with a known drug-resistant TB case or
- Newly diagnosed with MDR-TB within the last 30 days or
- Previously diagnosed with MDR-TB and failed TB treatment with positive sputum smear or culture after ≥3 months of a standard MDR-TB treatment regimen
- Patients meeting the above criteria will be screened by Xpert MTB/RIF or Xpert MTB/RIF Ultra. TB patients meeting the following criteria will be included in the study:
- A clear Mtb-positive and RIF-resistant or RIF-sensitive result by Xpert MTB/RIF or Xpert MTB/RIF Ultra
- Provision of informed consent;
- Production of an adequate quantity (\>3mL) of sputum
You may not qualify if:
- Participants will be excluded from the study if informed consent is not provided.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Foundation for Innovative New Diagnostics, Switzerlandlead
- Cepheidcollaborator
- PD Hinduja Hospital and Medical Research Centre, Mumbai, Indiacollaborator
- Phthisiopneumology Institute, Chisinau, Moldovacollaborator
- National Institute of Tuberculosis and Respiratory Disease, New Delhi, Indiacollaborator
- University of Witwatersrand, South Africacollaborator
Study Sites (1)
Institute of Pthisiopenumology
Chisinau, Moldova
Related Publications (1)
Penn-Nicholson A, Georghiou SB, Ciobanu N, Kazi M, Bhalla M, David A, Conradie F, Ruhwald M, Crudu V, Rodrigues C, Myneedu VP, Scott L, Denkinger CM, Schumacher SG; Xpert XDR Trial Consortium. Detection of isoniazid, fluoroquinolone, ethionamide, amikacin, kanamycin, and capreomycin resistance by the Xpert MTB/XDR assay: a cross-sectional multicentre diagnostic accuracy study. Lancet Infect Dis. 2022 Feb;22(2):242-249. doi: 10.1016/S1473-3099(21)00452-7. Epub 2021 Oct 7.
PMID: 34627496DERIVED
Biospecimen
Sputum will be collected from consenting, enrolled adult participants. Sputum samples may voluntarily be stored for up to 20 years.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 5, 2018
First Posted
November 2, 2018
Study Start
July 11, 2019
Primary Completion
August 18, 2020
Study Completion
August 18, 2020
Last Updated
May 19, 2021
Record last verified: 2020-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Upon publication of final study results
- Access Criteria
- The data will be shared with anyone who wishes to access the data.
Data sharing statement Individual, de-identified participant data will be shared, including data dictionaries. Other documents that have been made available include the study protocol and statistical analysis plan. Templates of the informed consent forms may be shared upon request. The data will be available immediately following publication with no end date. The data will be shared with anyone who wishes to access the data. The data will be available for any purpose of analyses. For data, please contact the corresponding author.