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Open Access 01-12-2022 | Tuberculosis | Study protocol

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

Authors: Annelies Van Rie, Elise De Vos, Emilyn Costa, Lennert Verboven, Felex Ndebele, Tim H. Heupink, Steven Abrams, Boitumelo Fanampe, Anneke Van der Spoel Van Dyk, Salome Charalambous, Gavin Churchyard, Rob Warren, SMARTT team

Published in: Trials | Issue 1/2022

Abstract

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

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Title: Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial
Authors: Annelies Van Rie
Elise De Vos
Emilyn Costa
Lennert Verboven
Felex Ndebele
Tim H. Heupink
Steven Abrams
Boitumelo Fanampe
Anneke Van der Spoel Van Dyk
Salome Charalambous
Gavin Churchyard
Rob Warren
SMARTT team
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Tuberculosis
Mycobacterium Tuberculosis
Tuberculosis
Rifampicin
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06793-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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