Triage Test for All Oral DR-TB Regimen (TRiAD Study)

NCT05175794 | Completed DMC

• 2 other identifiers: CAPRISA 094TRIAD
• Study Type: observational
• Target: 786
• Locations: 3 countries
• Sites: 4

Brief Summary

A Phase 4 operational study to assess the effectiveness, feasibility, acceptability, and cost effectiveness of the GeneXpert MTB/XDR (Xpert XDR; Cepheid) assay for rapid triage-and-treatment of DR-TB-A multi-centre, multi-country prospective cohort study

Conditions

Drug Resistant Tuberculosis; MDR-TB; XDR-TB; Tuberculosis

Keywords

GeneXpert; Diagnostic Tool

Outcome Measures

Primary Outcomes (2)

• Time to initiation

  Time to initiation of an appropriate all oral treatment regimen from date of first sputum collected

  4 years

• Proportion of patients with favorable treatment outcomes

  Proportion of patients with favorable treatment outcomes at month 12 from diagnosis

  4 years

Secondary Outcomes (13)

• Adverse Drug Reactions

  4 years

• Mortality

  4 years

• Time to culture Conversion

  4 years

• HR TB Prevalence

  4 years

• XDR TB Prevalence

  4 years

Study Arms (2)

Cohort 1

Participants that test positive for Mycobacterium tuberculosis (M.tb) with rifampicin resistance will be enrolled in Cohort 1 (n=880).

Diagnostic Test: Xpert® MTB/XDR

Cohort 2

Participants that test positive for M.tb that are rifampicin susceptible with isoniazid mono-resistance will be enrolled in Cohort 2 (n=400).

Diagnostic Test: Xpert® MTB/XDR

Interventions

Xpert® MTB/XDR DIAGNOSTIC_TEST

The Xpert MTB/XDR Assay, performed on the GeneXpert Instrument Systems, is a nested real-time polymerase chain reaction(PCR) in vitro diagnostic test for the detection of extensively drug resistant (XDR) Mycobacterium tuberculosis (MTB) complex DNA in unprocessed sputum samples or concentrated sediments prepared from sputum. In specimens where MTB is detected, the Xpert MTB/XDR Assay can also detect isoniazid (INH) resistance associated mutations in the katG and fabG1 genes, oxyRahpC intergenic region and inhA promoter; ethionamide (ETH) resistance associated with inhA promoter mutations only; fluoroquinolone (FLQ) resistance associated mutations in the gyrA and gyrB quinolone resistance determining regions (QRDR); and second line injectable drug (SLID) associated mutations in the rrs gene and the eis promoter region.

Also known as: Xpert MTB/XDR Assay, Xpert XDR

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Two screening strategies will be adopted: 1. Patients with suspected pulmonary TB or confirmed M.tb positive (\< 5 days since treatment initiation) will be screened and consented to provide an additional sputum sample for Xpert MTB/XDR testing. This will be in addition to the routine sample collected for GeneXpert MTB/RIF or Ultra testing 2. We will concurrently contact all patients with newly identified RR-TB during the study enrolment period directly for participation in this study (laboratory records)

You may qualify if:

• Ambulant adults ≥ 18 years of age
• Newly diagnosed PTB patients receiving less than 5 days of treatment since new diagnosis:
• Cohort 1: \< 5 days of DR-TB treatment
• Cohort 2: \< 5 days of INH mono-resistant TB treatment preceding study entry for the current TB episode, or
• Sputum positive (smear and or culture) TB patients classified as failing first line treatment
• Any currently available Nucleic Acid Amplification Tests for drug-resistance detection changes/assay positive for M.tb infection with:
• Cohort 1: at least Rifampicin resistance Cohort 2: Rifampicin susceptible co-occurring with INH, fluoroquinolone, ethionamide or aminoglycoside resistance (detected by Xpert XDR) occurring alone or in combination
• Capacity to provide informed consent
• HIV infected and uninfected participants are allowed in the study. Participants already on ART will be allowed in the study provided the ART regimen in use has no contraindications to the proposed TB drug regimen
• Willing to have samples collected, stored indefinitely, and used for research purposes
• Able to provide reasonable proof of identity (to satisfaction of study team member) at or prior to enrolment

You may not qualify if:

• Has a known severe allergy to any of the BPaL component drugs
• Has DST showing infection with a strain resistant to any of the component drugs
• Has TB meningitis, other central nervous system TB, or TB osteomyelitis; or
• Is pregnant or breastfeeding
• Is unable to take oral medications
• Persons with any other medical condition, precluding study participation based on investigator judgement
• Any co-existing condition that in the opinion of the attending clinician renders the participant unsuitable for participation in the study
• Co-enrolment in other interventional research studies

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead
• KNCV Tuberculosis Foundation: collaborator
• Amsterdam Institute for Global Health and Development: collaborator
• Ospedale San Raffaele: collaborator
• Foundation for Innovative New Diagnostics, Switzerland: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• University of St Andrews: collaborator
• Global Alliance for TB Drug Development: collaborator
• Wits Health Consortium (Pty) Ltd: collaborator
• Institute of Human Virology, Nigeria: collaborator
• Ethiopian Public Health Institute: collaborator

Study Sites (4)

Ethiopian Public Health Institute (EPHI)

Gulele, Addis Ababa, Ethiopia

Location

Institute of Human Virology Nigeria

Yaba, Lagos, Nigeria

Location

CAPRISA Springfield Research Clinic

Durban, KwaZulu-Natal, 4091, South Africa

Location

Clinical HIV Research Unit (CHRU), WITS Health Consortium

Bethelsdorp, Port Elizabeth, 6200, South Africa

Location

Related Publications (3)

• Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, Mendel CM, Egizi E, Moreira J, Timm J, McHugh TD, Wills GH, Bateson A, Hunt R, Van Niekerk C, Li M, Olugbosi M, Spigelman M; Nix-TB Trial Team. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. N Engl J Med. 2020 Mar 5;382(10):893-902. doi: 10.1056/NEJMoa1901814.

  PMID: 32130813 BACKGROUND

• Gillespie SH, Sabiiti W, Oravcova K. Mycobacterial Load Assay. Methods Mol Biol. 2017;1616:89-105. doi: 10.1007/978-1-4939-7037-7_5.

  PMID: 28600763 BACKGROUND

• Naidoo K, Naidoo A, Abimiku AG, Tiemersma EW, Gebhard A, Hermans SM, Sloan DJ, Ruhwald M, Georghiou SB, Okpokoro E, Agbaje A, Yae K, Tollera G, Moga S, Feyt H, Kachoka T, Letsoalo MP, Cabibbe AM, Perumal R, Shunmugam L, Cirillo DM, Foraida S, Sabiiti W, Ntinginya NE, Mtafya B, Bedru A, Gillespie SH; TRiAD Study Consortium. Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB. BMJ Open. 2024 Nov 27;14(11):e084722. doi: 10.1136/bmjopen-2024-084722.

  PMID: 39609025 DERIVED

Related Links

• WHO consolidated guidelines on tuberculosis

Biospecimen

Retention: SAMPLES WITH DNA

Participants will be asked to provide sputum samples for this study

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Extensively Drug-Resistant Tuberculosis; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Kogieleum Naidoo, MBCHB, PHD

  Deputy Director -CAPRISA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: January 4, 2022
• Study Start: May 26, 2022
• Primary Completion: December 31, 2024
• Study Completion: June 1, 2025
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

ZA (2); NG (1); ET (1)