Rifampicin Resistant TuberculosisSMARTTNCT05017324
Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial
A study testing WGS DST strategy in people with Rifampicin Resistant Tuberculosis and Drug-resistant Tuberculosis, run by Universiteit Antwerpen at 1 site in South Africa.
Trial summary
The primary aim of this pragmatic trial is to determine the effectiveness of a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rifampicin Resistant Tuberculosis, Drug-resistant Tuberculosis, Multidrug Resistant Tuberculosis
- What is being tested?
- WGS DST strategy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 248 participants
- Where
- 1 siteSouth Africa
- Study dates
- 21 Sep 2021to Jan 2025
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with RR-TB
- Diagnosed with pulmonary TB (PTB) or PTB plus extra-pulmonary TB (EPTB)
- ≥18 years of age
- Able to sign informed consent
- Not on TB treatment at time of enrolment
Who cannot join
- Patients diagnosed EPTB without pulmonary involvement
- Patients with TB Meningitis or TB of the bone.
- Has any condition that, in the opinion of the investigator or physician, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, interfere with achieving the study objectives or compromise patient safety.
Trial locations and contacts
1 site in 1 country.
Annelies Van Rie, PhD, MD contact
South Africa1 site, 1 recruiting
- Recruiting
Free State Department of Health Clinics
Bloemfontein, Free State
Salome Charalambous, PhD, +27 10 590 1389, SCharalambous@auruminstitute.org
About this study
The primary aim of this pragmatic trial is to determine the effectiveness of a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients.
The primary objective is to determine the effectiveness of this WGS DST strategy in patients diagnosed with RR-TB. We will additionally perform an exploratory health economics evaluation of both arms, and will determine the feasibility of the WGS DST strategy.
Read the detailed description
The trial will be a single blinded randomised controlled, pragmatic, medical device trial evaluating a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients. A total of 248 patients diagnosed with RR-TB in the South African Free State province will by randomised to one of two trial arms. 124 patients will be assigned to the intervention arm, consisting of a WGS DST strategy for diagnosing drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation. 124 patients will be assigned to the control arm where the diagnosis of Mtb drug resistance and individualisation of RR-TB treatment will happen according to the Standard of Care (SOC) procedures.
- Conditions
- Rifampicin Resistant Tuberculosis, Drug-resistant Tuberculosis, Multidrug Resistant Tuberculosis, Pulmonary Tuberculoses
- Being tested
- WGS DST strategy
- Keywords
- Whole Genome Sequencing, Drug Resistant Tuberculosis
- Medical subject headings
- Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WGS DST strategyDevice
WGS DST strategy for diagnosing the TB drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation
| Study group | Role | What they receive |
|---|---|---|
| WGS DST strategy | Experimental | WGS DST strategy for diagnosing the TB drug resistance profile and an individualised RR-TB treatment recommendation Receives: Device: WGS DST strategy |
| Standard of Care | No intervention | Standard of care diagnosis of the drug resistance profile and individualised treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Effectiveness of a WGS DST strategy for individualisation of RR-TB treatment
The effectiveness will be determined by the rate of change in time to positivity (TTP) over 6 months in the Mycobacterial Growth Indicator Tuber (MGIT) system [time from: Day 0 to Week 24].
The effectiveness of the WGS DST strategy will be determined by the rate of change in TTP in liquid media MGIT cultures of sputum samples collected during the first 6 months of treatment. The TTP will be used to determine the change in mycobacterial load using a non-linear mixed effect time-to-event model that provides a longitudinal representation of mycobacterial load (measured as TTP in MGIT) at weeks 2, 3, 4, 5, 6, 7, 8, 12, 16, 20 and 24
Measured: Day 0 to month 6 (6 months)
Secondary outcomes (2)
Health economic evaluation of a WGS DST strategy for individualization of RR-TB treatment
The difference in total cost over the entire treatment period from a patients and health system perspective between a WGS strategy and SOC strategy will be assessed by comparing costing data collected at month 1 of treatment, month 6 of treatment and at the end of treatment.
Measured: Start of treatment to end of treatment (which may vary from 6 months to over 11 months)
Impact of WGS strategy for individualisation of RR-TB treatment on Health related Quality of Life (HRQOL)
The difference in changes in health relates quality fo life will be assessed by comparing the change in HRQOL over time between patients randomised to the WGS and SOC strategies for individualisation of RR-TB treatment, using results of the EQ-5D-5L questionnaire collected at baseline, month 1, 2, 3, 4, 5, 6 and end of treatment.
Measured: Start of treatment to end of treatment (which may vary from 6 months to over 11 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2021
- Study start21 Sep 2021
- Primary completionDec 2022 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rifampicin Resistant TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Controled Phase 4 pragmatic single blinded medical device trial.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 248 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universiteit Antwerpen
- Sponsor type
- University, hospital or other
- Collaborators
- Aurum Institute, University of Stellenbosch, University of the Free State, Free State Department of Health
- Responsible party
- Principal investigator, Annelies Van Rie, Universiteit Antwerpen
- Investigators
- Gavin Churchyard, PhD, MD, Principal investigator, Aurum InstituteAnnelies Van Rie, PhD, MD, Principal investigator, Universiteit AntwerpenRob M Warren, PhD, Principal investigator, Stellenbosch University, MRCSalome Charalambous, PhD, Principal investigator, Aurum Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05017324
- Sponsor's protocol ID
- AUR1-11-248
- Other IDs
- T001018N, 2020-004084-10
- Acronym
- SMARTT
- Status last verified
- Oct 2021
- First submitted
- 22 Apr 2021
- Last updated
- 15 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The analysable individual patient data (IPD) will be made available, including WGS data (to be published on the European Nucleotide Archive (ENA)) and de-identified clinical and demographic IPD. This ensures an adit trial for summary results reporting, enables re-analyses of trial data and the possibility for combining the data with others for novel investigations.
Publications
Van Rie A, Conceicao EC, Ndebele F, Wells F, Paulse A, Mekonnen EG, Ngarega M, Trang TPH, Bohlela S, Sibeko Z, Segwaba P, Verboven L, Heupink TH, Fuertes MD, Rennie V, Dippenaar A, Rigouts L, Setlhare L, Ogunbayo AE, VanderSpoel Van Dyk A, Conradie F, Maartens G, Potgieter S, Black J, Fanampe B, Abrams S, Churchyard G, Warren R, Charalambous S. Whole genome sequencing precision medicine strategy to shorten treatment for rifampicin-resistant tuberculosis (SMARTT): a pragmatic, randomised, single-blind phase 4 trial. Lancet Respir Med. 2026 Jun;14(6):521-532. doi: 10.1016/S2213-2600(26)00095-0. Epub 2026 Apr 20.
PubMed 42026006Van Rie A, De Vos E, Costa E, Verboven L, Ndebele F, Heupink TH, Abrams S; SMARTT team; Fanampe B, Van der Spoel Van Dyk A, Charalambous S, Churchyard G, Warren R. Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial. Trials. 2022 Oct 8;23(1):864. doi: 10.1186/s13063-022-06793-w.
PubMed 36209235
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial
- ClinicalTrials.gov ID
- NCT05017324
- Acronym / sponsor ID
- SMARTT / AUR1-11-248
- Conditions
- Rifampicin Resistant Tuberculosis, Drug-resistant Tuberculosis, Multidrug Resistant Tuberculosis, Pulmonary Tuberculoses
- Keywords
- Whole Genome Sequencing, Drug Resistant Tuberculosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 248 participants (estimated)
- Lead sponsor
- Universiteit AntwerpenUniversity, hospital or other
- Collaborators
- Aurum Institute, University of Stellenbosch, University of the Free State, Free State Department of Health
- Study start
- 21 Sep 2021 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 23 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary aim of this pragmatic trial is to determine the effectiveness of a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients.
The primary objective is to determine the effectiveness of this WGS DST strategy in patients diagnosed with RR-TB. We will additionally perform an exploratory health economics evaluation of both arms, and will determine the feasibility of the WGS DST strategy.
Detailed description
The trial will be a single blinded randomised controlled, pragmatic, medical device trial evaluating a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients. A total of 248 patients diagnosed with RR-TB in the South African Free State province will by randomised to one of two trial arms. 124 patients will be assigned to the intervention arm, consisting of a WGS DST strategy for diagnosing drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation. 124 patients will be assigned to the control arm where the diagnosis of Mtb drug resistance and individualisation of RR-TB treatment will happen according to the Standard of Care (SOC) procedures.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized Controled Phase 4 pragmatic single blinded medical device trial.
| Arm | Type | Receives |
|---|---|---|
| WGS DST strategy | Experimental | Device: WGS DST strategyWGS DST strategy for diagnosing the TB drug resistance profile and an individualised RR-TB treatment recommendation |
| Standard of Care | No intervention | –Standard of care diagnosis of the drug resistance profile and individualised treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with RR-TB
- Diagnosed with pulmonary TB (PTB) or PTB plus extra-pulmonary TB (EPTB)
- ≥18 years of age
- Able to sign informed consent
- Not on TB treatment at time of enrolment
Key exclusion criteria (3 listed)
- Patients diagnosed EPTB without pulmonary involvement
- Patients with TB Meningitis or TB of the bone.
- Has any condition that, in the opinion of the investigator or physician, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, interfere with achieving the study objectives or compromise patient safety.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WGS DST strategyWGS DST strategy for diagnosing the TB drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation | Device | WGS DST strategy |
Primary outcome
The Effectiveness of a WGS DST strategy for individualisation of RR-TB treatment
Time frame: Day 0 to month 6 (6 months)
The effectiveness will be determined by the rate of change in time to positivity (TTP) over 6 months in the Mycobacterial Growth Indicator Tuber (MGIT) system [time from: Day 0 to Week 24]. The effectiveness of the WGS DST strategy will be determined by the rate of change in TTP in liquid media MGIT cultures of sputum samples collected during the first 6 months of treatment. The TTP will be used to determine the change in mycobacterial load using a non-linear mixed effect time-to-event model that provides a longitudinal representation of mycobacterial load (measured as TTP in MGIT) at weeks 2, 3, 4, 5, 6, 7, 8, 12, 16, 20 and 24
2 secondary outcomes
Health economic evaluation of a WGS DST strategy for individualization of RR-TB treatment
Time frame: Start of treatment to end of treatment (which may vary from 6 months to over 11 months)
Impact of WGS strategy for individualisation of RR-TB treatment on Health related Quality of Life (HRQOL)
Time frame: Start of treatment to end of treatment (which may vary from 6 months to over 11 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Derived from this study: PubMed 42026006Van Rie A, Conceicao EC, Ndebele F, Wells F, Paulse A, Mekonnen EG, Ngarega M, Trang TPH, Bohlela S, Sibeko Z, Segwaba P, Verboven L, Heupink TH, Fuertes MD, Rennie V, Dippenaar A, Rigouts L, Setlhare L, Ogunbayo AE, VanderSpoel Van Dyk A, Conradie F, Maartens G, Potgieter S, Black J, Fanampe B, Abrams S, Churchyard G, Warren R, Charalambous S. Whole genome sequencing precision medicine strategy to shorten treatment for rifampicin-resistant tuberculosis (SMARTT): a pragmatic, randomised, single-blind phase 4 trial. Lancet Respir Med. 2026 Jun;14(6):521-532. doi: 10.1016/S2213-2600(26)00095-0. Epub 2026 Apr 20.
- Derived from this study: PubMed 36209235Van Rie A, De Vos E, Costa E, Verboven L, Ndebele F, Heupink TH, Abrams S; SMARTT team; Fanampe B, Van der Spoel Van Dyk A, Charalambous S, Churchyard G, Warren R. Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial. Trials. 2022 Oct 8;23(1):864. doi: 10.1186/s13063-022-06793-w.
- Individual participant dataSharing planned: Yes. The analysable individual patient data (IPD) will be made available, including WGS data (to be published on the European Nucleotide Archive (ENA)) and de-identified clinical and demographic IPD. This ensures an adit trial for summary results reporting, enables re-analyses of trial data and the possibility for combining the data with others for novel investigations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annelies Van Rie, PhD, MD contact
Gavin Churchyard, PhD, MD principal investigator
Aurum Institute
Annelies Van Rie, PhD, MD principal investigator
Universiteit Antwerpen
Rob M Warren, PhD principal investigator
Stellenbosch University, MRC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing WGS DST strategy in people with Rifampicin Resistant Tuberculosis and Drug-resistant Tuberculosis, run by Universiteit Antwerpen at 1 site in South Africa.
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 5 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elise De Vos, MSc (0032477715350, elise.devos@uantwerpen.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Effectiveness of a WGS DST strategy for individualisation of RR-TB treatment (time frame: Day 0 to month 6 (6 months)). 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 NCT05017324, which also lists 2 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 15 Oct 2021.