Clinical trial NCT05017324: Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial
Official title: Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Rifampicin Resistant Tuberculosis
Drug-resistant Tuberculosis
Multidrug Resistant Tuberculosis
Pulmonary Tuberculoses
Keywords: Whole Genome Sequencing
Drug Resistant Tuberculosis
Lead sponsor: Universiteit Antwerpen
Sponsor class: OTHER
Collaborators: name: Aurum Institute
name: University of Stellenbosch
name: University of the Free State
name: Free State Department of Health
First posted: 2021-08-23
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controled Phase 4 pragmatic single blinded medical device trial.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The Effectiveness of a WGS DST strategy for individualisation of RR-TB treatment
timeFrame: Day 0 to month 6 (6 months)
Secondary outcomes:
measure: Health economic evaluation of a WGS DST strategy for individualization of RR-TB treatment
timeFrame: Start of treatment to end of treatment (which may vary from 6 months to over 11 months)
measure: Impact of WGS strategy for individualisation of RR-TB treatment on Health related Quality of Life (HRQOL)
timeFrame: Start of treatment to end of treatment (which may vary from 6 months to over 11 months)
Other outcomes:
Locations:
city: Bloemfontein
country: South Africa
facility: Free State Department of Health Clinics
state: Free State
Study officials:
affiliation: Aurum Institute
name: Gavin Churchyard, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universiteit Antwerpen
name: Annelies Van Rie, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stellenbosch University, MRC
name: Rob M Warren, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aurum Institute
name: Salome Charalambous, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.