Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial.

Autor: Van Rie A; Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. annelies.vanrie@uantwerpen.be., De Vos E; Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium., Costa E; South African Medical Research Council Centre for Tuberculosis Research, DST NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Verboven L; Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium., Ndebele F; Aurum Institute, Johannesburg, South Africa., Heupink TH; Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium., Abrams S; Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium., Fanampe B; Free State Department of Health, Bloemfontein, South Africa., Van der Spoel Van Dyk A; Universitas Academic Laboratory, National Health Laboratory Service and Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa., Charalambous S; Aurum Institute, Johannesburg, South Africa., Churchyard G; Aurum Institute, Johannesburg, South Africa., Warren R; South African Medical Research Council Centre for Tuberculosis Research, DST NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: Trials [Trials] 2022 Oct 08; Vol. 23 (1), pp. 864. Date of Electronic Publication: 2022 Oct 08.
DOI: 10.1186/s13063-022-06793-w
Abstrakt: Background: Rifampicin-resistant tuberculosis (RR-TB) remains an important global health problem. Ideally, the complete drug-resistance profile guides individualized treatment for all RR-TB patients, but this is only practised in high-income countries. Implementation of whole genome sequencing (WGS) technologies into routine care in low and middle-income countries has not become a reality due to the expected implementation challenges, including translating WGS results into individualized treatment regimen composition.
Methods: This trial is a pragmatic, single-blinded, randomized controlled medical device trial of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Subjects are 18 years or older and diagnosed with pulmonary RR-TB in four of the five health districts of the Free State province in South Africa. Participants are randomized in a 1:1 ratio to either the intervention (a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB) or control (RR-TB treatment according to the national South African guidelines). The primary effectiveness outcome is the bacteriological response to treatment measured as the rate of change in time to liquid culture positivity during the first 6 months of treatment. Secondary effectiveness outcomes include cure rate, relapse rate (recurrence of RR-TB disease) and TB free survival rate in the first 12 months following RR-TB treatment completion. Additional secondary outcomes of interest include safety, the feasibility of province-wide implementation of the strategy into routine care, and health economic assessment from a patient and health systems perspective.
Discussion: This trial will provide important real-life evidence regarding the feasibility, safety, cost, and effectiveness of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Given the pragmatic nature, the trial will assist policymakers in the decision-making regarding the integration of next-generation sequencing technologies into routine RR-TB care in high TB burden settings.
Trial Registration: ClinicalTrials.gov NCT05017324. Registered on August 23, 2021.
(© 2022. The Author(s).)
Databáze: MEDLINE
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