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| ID | Type | Description | Link |
|---|---|---|---|
| T001018N | Other Grant/Funding Number | TBM FWO | |
| 2020-004084-10 | EudraCT Number |
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| Name | Class |
|---|---|
| Aurum Institute | OTHER |
| University of Stellenbosch | OTHER |
| University of the Free State | UNKNOWN |
| Free State Department of Health |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| WGS DST strategy | Experimental | WGS DST strategy for diagnosing the TB drug resistance profile and an individualised RR-TB treatment recommendation |
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| Standard of Care | No Intervention | Standard of care diagnosis of the drug resistance profile and individualised treatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| WGS DST strategy | Device | WGS DST strategy for diagnosing the TB drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Day 0 to month 6 (6 months) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Start of treatment to end of treatment (which may vary from 6 months to over 11 months) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Elise De Vos, MSc | Contact | 0032477715350 | elise.devos@uantwerpen.be | |
| Annelies Van Rie, PhD, MD | Contact | annelies.vanrie@uantwerpen.be |
| Name | Affiliation | Role |
|---|---|---|
| Gavin Churchyard, PhD, MD | Aurum Institute | Principal Investigator |
| Annelies Van Rie, PhD, MD | Universiteit Antwerpen | Principal Investigator |
| Rob M Warren, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Free State Department of Health Clinics | Recruiting | Bloemfontein | Free State | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42026006 | Derived | 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. | |
| 36209235 |
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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.
From publication of the results of the primary up to 5 years thereafter
WGS: available on European Nucleotide Archive (ENA) Other data: access will be provided to researchers who have obtained Institutional Review Board (IRB) approval for analyses
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| ID | Term |
|---|---|
| D018088 | Tuberculosis, Multidrug-Resistant |
| D014397 | Tuberculosis, Pulmonary |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| UNKNOWN |
Randomized Controled Phase 4 pragmatic single blinded medical device trial.
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| 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. | Start of treatment to end of treatment (which may vary from 6 months to over 11 months) |
| Stellenbosch University, MRC |
| Principal Investigator |
| Salome Charalambous, PhD | Aurum Institute | Principal Investigator |
| Derived |
| Van 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. |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |