Feasibility and Accuracy of a Novel Xpert Cartridge ((XpertDST))

Feasibility and Accuracy of a Novel Xpert Cartridge for Rapid Molecular Detection of Drug Resistant Mycobacterium Tuberculosis in Sputum

Consenting adults will be interviewed for demographic and medical information, and then will be asked to provide two expectorated sputum specimens. In the study laboratory, sputa will be tested using conventional and investigational diagnostic tests for tuberculosis.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Device: Investigational Xpert DST test

Detailed Description

• For each of isoniazid, ofloxacin, moxifloxacin, amikacin, and kanamycin: sensitivity and specificity of the investigational Xpert test for detection of drug resistance, using phenotypic drug susceptibility testing as the reference comparator
• For each of isoniazid, ofloxacin, moxifloxacin, amikacin, and kanamycin: sensitivity and specificity of the investigational Xpert test for detection of drug resistance, using mycobacterial DNA sequencing as the reference comparator
• Sensitivity and specificity, for detection of M. tuberculosis in sputum, of the investigational Xpert test and of the conventional Xpert MTB/RIF test, using culture as the reference comparator
• Diagnostic yield (for tuberculosis) of the investigational Xpert test and of the conventional Xpert MTB/RIF test
• For the investigational Xpert test, the proportion of specimens with a result of 'invalid' and the proportion of specimens with a result of 'error'
• Proportion of study participants with M. tuberculosis detected in sputum
• Proportion of participants with drug resistant tuberculosis, by drug resistance pattern and by tuberculosis categorization (new case or not new case)

• Study Type: Observational
• Enrollment (Actual): 401

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults with clinical signs and/or symptoms of pulmonary TB

Description

Inclusion Criteria:

• Individuals must meet all of the following inclusion criteria in order to be eligible to participate:

  • Age ≥ 19 years (age of majority) if enrolled in South Korea; age ≥ 18 years (age of majority) if enrolled in China
  • Provision of informed consent
  • Clinical signs and/or symptoms suggestive of pulmonary tuberculosis
  • Meets one of the following criteria:

A. Suspected or confirmed new pulmonary tuberculosis case who has received anti-tuberculosis drugs for less than 3 (three) days (target enrollment for Group A is approximately 50 participants).

B. Confirmed pulmonary tuberculosis with documented rifampin resistance, who has received anti-tuberculosis drugs for 31 days or less C. History of prior tuberculosis PLUS ongoing signs and/or symptoms of pulmonary tuberculosis PLUS suspected drug resistance

Exclusion Criteria:

• Inability to provide a sputum specimen

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case detection group; Suspected or confirmed new pulmonary tuberculosis cases who have received anti-tuberculosis drugs for less than 3 (three) days and provide up to two expectorated sputum specimens. One investigational Xpert DST test and one Xpert MTB/RIF test were performed directly on the same sputum specimen; in addition, one smear microscopy test, one mycobacterial liquid culture, and one solid culture were performed after digestion and decontamination of sputum.	Device: Investigational Xpert DST test; One investigational test performed directly on the same sputum specimen.
Drug resistance risk group; Confirmed pulmonary tuberculosis cases with documented rifampin resistance, who have received anti-tuberculosis drugs for 31 days or less and/or history of prior tuberculosis PLUS ongoing signs and/or cases with symptoms of pulmonary tuberculosis PLUS suspected drug resistance and provide up to two expectorated sputum specimens. One investigational Xpert DST test and one Xpert MTB/RIF test were performed directly on the same sputum specimen; in addition, one smear microscopy test, one mycobacterial liquid culture, and one solid culture were performed after digestion and decontamination of sputum.	Device: Investigational Xpert DST test; One investigational test performed directly on the same sputum specimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity	sensitivity and specificity of the investigational Xpert DST test for detection of drug resistance, using phenotypic drug susceptibility testing, mycobacterial DNA sequencing, and MTB/RIF test as the reference comparator	10 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Diagnostic yield (for tuberculosis) of the investigational Xpert test and of the conventional Xpert MTB/RIF test	10 months
the proportion of specimens with a result of 'invalid' and the proportion of specimens with a result of 'error'	10 months
Proportion of study participants with TB and DRTB	10 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Boston Medical Center

Publications and helpful links

General Publications

• Xie YL, Chakravorty S, Armstrong DT, Hall SL, Via LE, Song T, Yuan X, Mo X, Zhu H, Xu P, Gao Q, Lee M, Lee J, Smith LE, Chen RY, Joh JS, Cho Y, Liu X, Ruan X, Liang L, Dharan N, Cho SN, Barry CE 3rd, Ellner JJ, Dorman SE, Alland D. Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis. N Engl J Med. 2017 Sep 14;377(11):1043-1054. doi: 10.1056/NEJMoa1614915.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2014
• Primary Completion (Actual): June 15, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 29, 2014

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: NA_0008420 (Other Identifier: Johns Hopkins University)

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