- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05175794
Triage Test for All Oral DR-TB Regimen (TRiAD Study)
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Kogieleum Naidoo, MBCHB, PHD
- Phone Number: 0707 +27 31 655 0707
- Email: kogie.naidoo@caprisa.org
Study Contact Backup
- Name: Anushka Naidoo, PHD
- Phone Number: 5553 031-655 0553
- Email: anushka.naidoo@caprisa.org
Study Locations
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Addis Ababa
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Gulele, Addis Ababa, Ethiopia
- Recruiting
- Ethiopian Public Health Institute (EPHI)
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Contact:
- Getachew Tollera, PHD
- Email: getachewtollera@gmail.com
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Lagos State
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Yaba, Lagos State, Nigeria
- Recruiting
- Institute of Human Virology Nigeria
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Contact:
- Alash'le Abimiku, PHD,BSc,MSc
- Phone Number: 4759 +234 813 944 4759
- Email: aabimiku@ihv.umaryland.edu
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Contact:
- Evaezi Okpokoro
- Phone Number: 4759 +234 813 944 4759
- Email: eokpokoro@ihvnigeria.org
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KwaZulu-Natal
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Durban, KwaZulu-Natal, South Africa, 4091
- Recruiting
- CAPRISA Springfield Research Clinic
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Contact:
- Anushka Naidoo, PHD
- Phone Number: 5553 031-655 0553
- Email: anushka.naidoo@caprisa.org
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Contact:
- Kogieleum Naidoo, MBCHB, PHD
- Phone Number: 0707 +21 655 0707
- Email: kogie.naidoo@caprisa.org
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Port Elizabeth
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Bethelsdorp, Port Elizabeth, South Africa, 6200
- Recruiting
- Clinical HIV Research Unit (CHRU), WITS Health Consortium
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Contact:
- Francesca M Conradie, MBCHB
- Phone Number: 8800 +27 11 276 8800
- Email: fconradie@witshealth.co.za
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Contact:
- Tasnim Badat, MBCHB
- Phone Number: 3760 +27 41 492 3760
- Email: tbadat@witshealth.co.za
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Two screening strategies will be adopted:
- 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
- We will concurrently contact all patients with newly identified RR-TB during the study enrolment period directly for participation in this study (laboratory records)
Description
Inclusion Criteria:
- 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
Exclusion criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Cohort 1
Participants that test positive for Mycobacterium tuberculosis (M.tb) with rifampicin resistance will be enrolled in Cohort 1 (n=880).
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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.
Other Names:
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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).
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to initiation
Time Frame: 4 years
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Time to initiation of an appropriate all oral treatment regimen from date of first sputum collected
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4 years
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Proportion of patients with favorable treatment outcomes
Time Frame: 4 years
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Proportion of patients with favorable treatment outcomes at month 12 from diagnosis
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4 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Drug Reactions
Time Frame: 4 years
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Incidence of adverse drug reactions documented during all oral treatment
|
4 years
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Mortality
Time Frame: 4 years
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All cause mortality documented during treatment and follow up
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4 years
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Time to culture Conversion
Time Frame: 4 years
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Time specific rates of culture conversion
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4 years
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HR TB Prevalence
Time Frame: 4 years
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Prevalence of HR TB (cohort 2)
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4 years
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XDR TB Prevalence
Time Frame: 4 years
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Prevalence of XDR TB (cohort 2)
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4 years
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Proportion of patients with Bedaquiline and linezolid resistance not eligible for short course treatment
Time Frame: 4 years
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Proportion of patients with Bedaquiline and linezolid resistance not eligible for short course treatment
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4 years
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Clinical utility of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to routine culture to monitor DR-TB treatment response
Time Frame: 4 years
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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
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4 years
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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
Time Frame: 4 years
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Feasibility of TB-MBLA Assessed by comparison to liquid culture with respect to accuracy, result turn-around time, failure rates.
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4 years
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Accuracy of Xpert XDR testing compared to WGS
Time Frame: 4 years
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The performance of Xpert XDR will be compared to Culture DST, LPA and Next Generation Sequencing.
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4 years
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Quality of Xpert XDR testing
Time Frame: 4 years
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Quality of Xpert XDR testing will be assessed using:
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4 years
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Resistance profile of sputum samples for identification of drug resistance mutations as per pre-existing probes within the Xpert XDR assay
Time Frame: 4 years
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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:
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4 years
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Cost effectiveness
Time Frame: 4 years
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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 |
4 years
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Operational Feasibility of patient triaging
Time Frame: 4 years
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The Operational Cost including Infrastructure and Human resource requirements for the study approach.
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4 years
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Kogieleum Naidoo, MBCHB, PHD, Deputy Director -CAPRISA
Publications and helpful links
General 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CAPRISA 094
- TRIAD (Other Identifier: CAPRISA)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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