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, Annelies, De Vos, Elise, Costa, Emilyn, Verboven, Lennert, Ndebele, Felex, Heupink, Tim, Abrams, Steven, Maraba, Noriah, Makkan, Heeran, Beattie, Trevor, Sibeko, Zandile Rachel, Bohlela, S’thabiso, Segwaba, Pulane, Ogunbayo, Emmanuel Ayodeji, Mhlambi, Nomadlozi, Wells, Felicia, Rigouts, Leen, Maartens, Gary, Conradie, Francesca, Black, John, Potgieter, Sam, Fanampe, Boitumelo, Van der Spoel Van Dyk, Anneke, Charalambous, Salome, Churchyard, Gavin, Warren, Rob
Přispěvatelé: Van Rie, A, De Vos, E, Costa, E, Verboven, Lennert, Ndebele, F, Heupink, TH, ABRAMS, Steven, Fanampe, B, Van Dyk, AV, Charalambous, S, Churchyard, G, Warren, R, SMARTT team
Rok vydání: 2022
Předmět:
Zdroj: Trials
ISSN: 1745-6215
Popis: 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. Funding The trial is funded by the Research foundation Flanders (FWO) TBM (Applied Biomedical Research with a Primary Social finality) grant number T001018N and FWO Odysseus grant number G0F8316N. The funding body played no role in the design of the study and will not play any role in data collection, analysis, and interpretation of data and in writing the manuscript. Acknowledgements We would like to thank all MDR-TB doctors, MDR-TB nurses, and MDR-TB coordinators of the health districts of the Free State, Noor Zakhura, and Mothusi Masiba for their time and dedication to the study. We also want to thank Keertan Dheda, Gunar Gunther, and Marie-Christin Payen who volunteered to be a member of the data monitoring and safety board. We thank Kelly Dooley and Steven Callens for their contribution to the development of the treatment recommender. We thank Philippe Beutels for his advice on the health economics assessment of the intervention and Ruben Cartuyvels for the development of the treatment recommender web interface. SMARTT group authorship: Noriah Maraba1, Heeran Makkan1, Trevor Beattie1, Zandile Rachel Sibeko1, S’thabiso Bohlela1, Pulane Segwaba1, Emmanuel Ayodeji Ogunbayo2, Nomadlozi Mhlambi2, Felicia Wells3, Leen Rigouts4, Gary Maartens5, Francesca Conradie6, John Black7, Sam Potgieter8. 1Aurum Institute, Johannesburg, South Africa; 2Universitas Academic Laboratory, National Health Laboratory Service and Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; 3South 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; 4Unit of Mycobacteriology, Dept of Biomedical Sciences, Belgium, Institute of Tropical medicine, Antwerp, 5Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa; 6Clinical HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg; 7Department of Medicine, Livingstone Hospital, Port Elizabeth, South Africa; 8Department of Internal Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa Trial registration: ClinicalTrials.gov NCT05017324. Registered on August 23, 2021.
Databáze: OpenAIRE
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