Clinical Evaluation of the Truenat Point-of-care Tuberculosis Diagnostic Test

Prospective, Multicentre Trial to Assess the Diagnostic Accuracy of the Truenat Assays at Intended Settings of Use

Consenting adults presenting with signs and symptoms compatible with pulmonary tuberculosis will be interviewed for demographic and medical information, and then will be asked to provide 3-4 expectorated sputum specimens. In the study laboratory, sputa will be tested using conventional and investigational diagnostic tests for tuberculosis and rifampin resistance.

Study Overview

• Status: Completed
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Diagnostic test: Truenat MTB

• Study Type: Observational
• Enrollment (Actual): 1926

Contacts and Locations

Study Locations

• Ethiopia
  • Addis Ababa, Ethiopia
    • EPHI
• India
  • Ahmedabad, India
    • State TB and Demonstration Center
  • Chennai, India
    • NIRT
  • Mumbai, India
    • PD Hinduja Hospital

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

Patients will be recruited from outpatient TB clinics at district or regional health facilities. Given the important role of the private sector in India, 1 private laboratory will be included in the trial which is an MDR reference hospital.

This is a multi-centre trial conducted in four countries: India, Peru, Papua New Guinea and Ethiopia. Countries were selected to be globally representative of the TB epidemic.

Description

Inclusion Criteria:

Case Detection Group:

• Age 18 years or above
• Clinical suspicion of pulmonary TB (including cough ≥2 week and at least 1 other symptom typical of TB);
• Willingness to provide 3-4 sputum specimens at enrolment;
• Willingness to have a trial follow-up visit approximately 2 months after enrolment;
• Provision of informed consent.

Drug Resistant TB Group:

In addition to the criteria of the Case Detection Group, participants should also meet the following conditions:

• Non-converting pulmonary TB cases (category I and category II failures)

Exclusion Criteria:

Case Detection Group:

• Receipt of any dose of TB treatment within 60 days prior to enrolment (even if within last two days only).

Drug Resistant TB Group:

• Receipt of any dose of MDR-TB treatment within 60 days prior to enrolment (even if within last two days only).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case Detection Group; Clinical suspicion of pulmonary TB (including cough ≥2 week and at least 1 other symptom typical of TB). Only participants who have not received any form of TB treatment within the prior 60 days will be enrolled	Diagnostic test: Truenat MTB; The Truenat MTB (including both MTB and MTB Plus) and the MTB-RIF Dx reflex assays (Molbio Diagnostics; Bangalore, India) utilize chip-based real-time micro-PCR for detection of tuberculosis (TB) and rifampicin (RIF) resistance from DNA extracted (on a separate device) from sputum samples. The Truenat MTB assay targets a single copy gene while the MTB Plus assay combines detection of a single copy and multi-copy gene.; Other Names: Truenat MTB Plus; Truenat MTB-RIF Dx
Drug Resistant TB Group; In addition to the criteria of the Case Detection Group, participants should also meet the following conditions: Non-converting pulmonary TB cases (category I and category II failures).	Diagnostic test: Truenat MTB; The Truenat MTB (including both MTB and MTB Plus) and the MTB-RIF Dx reflex assays (Molbio Diagnostics; Bangalore, India) utilize chip-based real-time micro-PCR for detection of tuberculosis (TB) and rifampicin (RIF) resistance from DNA extracted (on a separate device) from sputum samples. The Truenat MTB assay targets a single copy gene while the MTB Plus assay combines detection of a single copy and multi-copy gene.; Other Names: Truenat MTB Plus; Truenat MTB-RIF Dx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy (Sensitivity and Specificity) of the Truenat MTB assay	Estimate diagnostic accuracy of the Truenat assays (MTB and MTB Plus) for Mycobacterium tuberculosis (MTB) detection among individuals undergoing evaluation for pulmonary TB, using a culture reference standard	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy (Sensitivity and Specificity) of the Truenat MTB-RIF Dx assay	Estimate diagnostic accuracy of the Truenat MTB-RIF Dx assay for RIF resistance detection among individuals undergoing evaluation for pulmonary TB and DR TB, using phenotypic/genotypic drug susceptibility testing (DST) .	Day 1
Diagnostic accuracy (Sensitivity and Specificity) of the Truenat MTB assay compared to Xpert MTB/RIF	Compare the diagnostic accuracy of the Truenat assays (MTB and MTB Plus) to that of Xpert MTB/RIF, using a reference standard of culture for TB diagnosis and phenotypic/genotypic DST for detection of RIF resistance.	Day 1
Diagnostic accuracy (Sensitivity and Specificity) of the Truenat MTB-RIF Dx assay compared to Xpert MTB/RIF	Compare the diagnostic accuracy of the Truenat MTB-RIF Dx assay to that of Xpert MTB/RIF, using a reference standard of culture for TB diagnosis and phenotypic/genotypic DST for detection of RIF resistance.	Day 1
Time to TB detection and RIF resistance detection.	Assess patient important outcomes, including time to detection of TB and RIF resistance.	Day 1

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Universidad Peruana Cayetano Heredia; Burnet Institute; National Institute for Research in Tuberculosis, Chennai, India; Ethiopian Public Health Institute; PD Hinduja Hospital and Medical Research Centre, Mumbai, India

Publications and helpful links

General Publications

• Nikam C, Jagannath M, Narayanan MM, Ramanabhiraman V, Kazi M, Shetty A, Rodrigues C. Rapid diagnosis of Mycobacterium tuberculosis with Truenat MTB: a near-care approach. PLoS One. 2013;8(1):e51121. doi: 10.1371/journal.pone.0051121. Epub 2013 Jan 21.
• Nikam C, Kazi M, Nair C, Jaggannath M, M M, R V, Shetty A, Rodrigues C. Evaluation of the Indian TrueNAT micro RT-PCR device with GeneXpert for case detection of pulmonary tuberculosis. Int J Mycobacteriol. 2014 Sep;3(3):205-10. doi: 10.1016/j.ijmyco.2014.04.003. Epub 2014 Jun 2.
• Penn-Nicholson A, Gomathi SN, Ugarte-Gil C, Meaza A, Lavu E, Patel P, Choudhury B, Rodrigues C, Chadha S, Kazi M, Macé A, Nabeta P, Boehme C, Gangakhedkar RR, Sarin S, Tesfaye E, Gotuzzo E, du Cros P, Tripathy S, Ruhwald M, Singh M, Denkinger CM, Schumacher SG; Truenat Trial Consortium; Members of the Truenat Trial Consortium:. A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays. Eur Respir J. 2021 Nov 4;58(5). pii: 2100526. doi: 10.1183/13993003.00526-2021. Print 2021 Oct.
• Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N, Schumacher SG, Ochodo EA, Haraka F, Zwerling AA, Pai M, Steingart KR, Horne DJ. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis. Cochrane Database Syst Rev. 2021 Feb 22;2:CD009593. doi: 10.1002/14651858.CD009593.pub5.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): July 9, 2020
• Study Completion (Actual): July 9, 2020

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 6, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: 7212-03/2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No