AzTrials
AzTrials

Drug Resistant TuberculosisNCT05175794

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

An observational study of Drug Resistant Tuberculosis and MDR-TB, run by Centre for the AIDS Programme of Research in South Africa at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Drug Resistant Tuberculosis, MDR-TB, XDR-TB
What is being tested?
Xpert® MTB/XDR
Type of treatment
Injection or infusion
How many people
786 participants
Where
4 sitesin 3 countries
Study dates
26 May 2022to 1 Jun 2025
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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)

Who may be able to join

  • 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:
Show all 11Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

South Africa2 sites

  • Clinical HIV Research Unit (CHRU), WITS Health Consortium

    Bethelsdorp, Port Elizabeth, 6200

  • CAPRISA Springfield Research Clinic

    Durban, KwaZulu-Natal, 4091

Other trials in South Africa

Ethiopia1 site

  • Ethiopian Public Health Institute (EPHI)

    Gulele, Addis Ababa

Other trials in Ethiopia

Nigeria1 site

  • Institute of Human Virology Nigeria

    Yaba, Lagos

Other trials in Nigeria

About this study

Official title: 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 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

Read the detailed description

The TriAD study is a multi-center, multi-country Prospective Pragmatic Cohort study assessing the effectiveness, feasibility, acceptability, and cost-effectiveness of implementing the Xpert MTB/XDR (Xpert XDR; Cepheid) assay for rapid triage-and-treatment with short, all- oral drug resistant tuberculosis (DR-TB) treatment. The proposed study aims to screen approximately 4800 GeneXpert MTB/RIF or Ultra MTB-positive (irrespective of rifampicin resistance status) patients from 9 study sites in South Africa, Nigeria and Ethiopia to enrol 880 rifampicin resistant (RR) and 400 isoniazid mono-resistant (HR) patients over a period of 12-18 months. The Xpert XDR assay, a rapid genotypic test, will be implemented as a reflex test to detect resistance to isoniazid, fluoroquinolones and second-line injectable agents to provide rapid genotypic susceptibility testing for DR-TB detection. Patients that test positive for Mycobacterium tuberculosis with rifampicin resistance will be enrolled in Cohort 1 (n=880). Patients that test positive for Mycobacterium tuberculosis that are rifampicin susceptible with isoniazid mono-resistance will be enrolled in Cohort 2 (n=400). Results from the Xpert XDR assay will be used to guide selection of appropriate, evidence-based, all-oral DR-TB treatment regimens of shortest possible duration. The tuberculosis molecular bacterial load assay (TB-MBLA) will be used as an adjunct to provide bacillary load monitoring over the course of treatment to assess real-time treatment response. Operational research will provide information about the feasibility, acceptability and cost-effectiveness to inform policies and guidelines for programmatic implementation of the triage-and-treat model.

Being tested
Xpert® MTB/XDR
Keywords
GeneXpert, Diagnostic Tool
Medical subject headings
Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis, Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Xpert® MTB/XDRDiagnostic test

    Also called Xpert MTB/XDR Assay, Xpert XDR

    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.

Study groups in NCT05175794
Study groupRoleWhat they receive
Cohort 1Participants that test positive for Mycobacterium tuberculosis (M.tb) with rifampicin resistance will be enrolled in Cohort 1 (n=880).
Receives: Diagnostic Test: Xpert® MTB/XDR
Cohort 2Participants that test positive for M.tb that are rifampicin susceptible with isoniazid mono-resistance will be enrolled in Cohort 2 (n=400).
Receives: Diagnostic Test: Xpert® MTB/XDR

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to initiation

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

    Measured: 4 years

  2. Proportion of patients with favorable treatment outcomes

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

    Measured: 4 years

Secondary outcomes (13)

  1. Adverse Drug Reactions

    Incidence of adverse drug reactions documented during all oral treatment

    Measured: 4 years

  2. Mortality

    All cause mortality documented during treatment and follow up

    Measured: 4 years

  3. Time to culture Conversion

    Time specific rates of culture conversion

    Measured: 4 years

  4. HR TB Prevalence

    Prevalence of HR TB (cohort 2)

    Measured: 4 years

  5. XDR TB Prevalence

    Prevalence of XDR TB (cohort 2)

    Measured: 4 years

  6. Proportion of patients with Bedaquiline and linezolid resistance not eligible for short course treatment

    Proportion of patients with Bedaquiline and linezolid resistance not eligible for short course treatment

    Measured: 4 years

  7. Clinical utility of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to routine culture to monitor DR-TB treatment response

    Quantitative results from the TB-MBLA, a real-time quantitative PCR (RT-qPCR) assay, that detects and quantifies killing of 16S rRNA from both viable replicating and dormant M. tuberculosis in patient sputum during treatment, will be compared to routine culture in monitoring treatment response

    Measured: 4 years

  8. Feasibility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) will be compared to routine culture in bacteriological follow-up for people on DR-TB treatment

    Feasibility of TB-MBLA Assessed by comparison to liquid culture with respect to accuracy, result turn-around time, failure rates.

    Measured: 4 years

  9. Accuracy of Xpert XDR testing compared to WGS

    The performance of Xpert XDR will be compared to Culture DST, LPA and Next Generation Sequencing.

    Measured: 4 years

  10. Quality of Xpert XDR testing

    Quality of Xpert XDR testing will be assessed using:

    1. indeterminate rates measured by the number of Xpert XDR tests regarded as invalid divided by the total number of Xpert XDR tests performed
    2. Contamination rates or frequency of DNA contamination: number of Xpert XDR tests flagging contamination divided by the total number of Xpert XDR tests performed or events
    3. performance variation will be measured by performance in discrimination of (i) INH resistance compared to culture across study sites, (ii) aminoglycoside resistance compared to culture across study sites and (iii) fluroquinolone resistance compared to culture across study sites

    Measured: 4 years

  11. Resistance profile of sputum samples for identification of drug resistance mutations as per pre-existing probes within the Xpert XDR assay

    Cultured isolates from the same sputum sample will undergo WGS sequencing to identify additional resistance mutations to new and re-purposed drugs. The endpoints measured for this objective includes:

    1. Frequency of detection of additional resistance conferring mutations by WGS not detected by Xpert XDR
    2. Impact of these previously undetected mutation on conferring resistance to the new drugs in the bedaquiline, pretomanid and linezolid regimen

    Measured: 4 years

  12. Cost effectiveness

    Data for Costing studies will be collected through semi-structured interviews of key informants and document review. Methods will include a construction of incremental cost effectiveness ratios (ICER) and CE-model to estimate the costs and benefits from a societal perspective, generalizable to other settings.

    timely initiated on treatment

    Measured: 4 years

  13. Operational Feasibility of patient triaging

    The Operational Cost including Infrastructure and Human resource requirements for the study approach.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2022
  2. Study start26 May 2022
  3. Primary completion31 Dec 2024
  4. Study completion1 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
786 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05175794
Sponsor's protocol ID
CAPRISA 094
Other IDs
TRIAD
Status last verified
Jun 2025
First submitted
22 Sep 2021
Last updated
26 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 32130813

  • 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.

    PubMed 28600763

  • 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.

    PubMed 39609025

Questions about this trial

What is this clinical trial studying?

An observational study of Drug Resistant Tuberculosis and MDR-TB, run by Centre for the AIDS Programme of Research in South Africa at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in South Africa, Ethiopia, Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to initiation (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05175794, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in