Testing drug-resistant tuberculosis sputum to guide individual treatment
Tests a sputum sequencing method to choose treatment for drug-resistant tuberculosis in adults.
Plain-language title generated from the registry record
Registry title: Test to Treat TB: Impact of Sputum Sequencing-guided Individualised Therapy on Outcomes in Drug-resistant Tuberculosis
Key facts
- Where
- Cape Town, South AfricaSee the site
Where in South Africa
- University of Cape TownCape Town, South AfricaNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- University of Cape Town
- Trial code
- NCT05007795
- Record updated
- 6 May 2026
- Original description
Resistance to anti-tuberculosis drugs is a continually growing problem. Multidrug-resistant tuberculosis (MDRTB) is resistance to at least rifampicin and isoniazid, and extensively drug-resistant TB is additional resistance to a fluoroquinolone and a second injectable line drug. Methods currently employed in testing for resistance are inadequate and a contributing factor to the 40-50% MDR-TB treatment success rate. Current drug susceptibility testing methods are slow for most drugs, taking weeks. Rapid molecular methods such as the line probe assays, e.g. Hain GenoType MDRTBplus and sl, provide resistant calls to only a limited number of drugs, and are often less useful in smear negative patients.Read full original descriptionShow less
Test to Treat TB: Impact of Sputum Sequencing-guided Individualised Therapy on Outcomes in Drug-resistant Tuberculosis (TB): a Proof of Concept Randomized Controlled Trial
Resistance to anti-tuberculosis drugs is a continually growing problem. Multidrug-resistant tuberculosis (MDRTB) is resistance to at least rifampicin and isoniazid, and extensively drug-resistant TB is additional resistance to a fluoroquinolone and a second injectable line drug. Methods currently employed in testing for resistance are inadequate and a contributing factor to the 40-50% MDR-TB treatment success rate. Current drug susceptibility testing methods are slow for most drugs, taking weeks. Rapid molecular methods such as the line probe assays, e.g. Hain GenoType MDRTBplus and sl, provide resistant calls to only a limited number of drugs, and are often less useful in smear negative patients.
Molecular technologies such as sequencing can provide a comprehensive readout of drug resistance and are able to detect resistant populations at very low levels (≤1%), thus enabling individualized therapy. This can be done directly from sputum. Targeted sequencing amplifies regions of genomic DNA associated with resistance prior to sequencing. Rapid analytic software is used to process the raw sequence data, identify resistance causing mutations and provide a readout of clinically relevant information. However, the feasibility, and more importantly the impact, of this approach has not been evaluated in a clinical trial to establish proof of concept.
Aim 1: To conduct a randomised controlled trial to determine the impact of sputum-based targeted sequencing in detecting resistance to second-line TB drugs compared to the current programmatic standard of care (Hain MDRTBplus/sl and adjunct phenotypic drug susceptibility testing) when used to inform of treatment for MDR-TB.
Aim 2: To compare currently available drug resistant sequencing pipelines for diagnostic accuracy, sensitivity, specificity and predictive value as compared to culture based phenotypic drug susceptibility testing.
Aim 3: To compare the feasibility, accuracy, turn-aroundtime, and cost implications of the above-mentioned diagnostic approaches.
Inclusion: Subjects are required to meet ALL of the following inclusion criteria to participate:; Newly diagnosed culture and/or Xpert/MTB Ultra positive pulmonary TB; Rifampicin resistance detected using GeneXpert; Provide written informed consent prior to all trial-related procedures; Male or female aged 18 years and older; Patients on TB treatment for less than or equal to 7 days; Patients receiving both the shorter and longer MDR-TB regimen will be eligible.
Exclusion: A subject who in the opinion of the investigator is unlikely to cope with regular visits to the trial site either because of travel constraints, or drug or alcohol abuse, or other reason; Currently on MDR-TB treatment and completed 7 days of treatment; Having participated in other clinical studies within 8 weeks prior to trial start where investigational agents were used that may potentially impact current trial outcome; Any participant with a clinically significant pre-existing medical condition that, in the opinion of the investigator, may be significantly worsened by the patient's participation in the study; Any pre-existing laboratory abnormality, which in the opinion of the investigator will place the participant at risk (see detailed protocol for grade of abnormality); Subjects will be excluded from participation if they meet ANY of the following criteria:; Any subject with a Karnofsky score < 50; Participant who is pregnant, breast-feeding (and not willing to stop), or planning to conceive a child within 6 months of cessation of treatment.