Effectiveness and cardiac safety of bedaquiline-based therapy for drug-resistant tuberculosis: a prospective cohort study. Brust, J. C M, Gandhi, N. R, Wasserman, S., Maartens, G., Omar, S. V, Ismail, N. A, Campbell, A., Joseph, L., Hahn, A., Allana, S., Hernandez-Romieu, A. C, Zhang, C., Mlisana, K., Viljoen, C. A, Zalta, B., Ebrahim, I., Franczek, M., Master, I., Ramangoaela, L., te Riele, J., & Meintjes, G. A Clinical Infectious Diseases, Clin Infect Dis, apr, 2021.
Effectiveness and cardiac safety of bedaquiline-based therapy for drug-resistant tuberculosis: a prospective cohort study [link]Paper  doi  abstract   bibtex   
Background: Bedaquiline improves treatment outcomes in patients with rifampin-resistant TB (RR-TB) but prolongs the QT-interval and carries a black-box warning by the U.S. Food and Drug Administration. The World Health Organization recommends that all patients with RR-TB receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. Methods: We conducted an observational cohort study of RR-TB patients from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, including electrocardiograms (ECGs) performed in triplicate at four time points during bedaquiline therapy. Participants were followed until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT-prolongation, defined as any QTcF\textgreater500 ms or an absolute change from baseline (△ QTcF) \textgreater60 ms. Results: We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant (XDR) TB. Most participants (97%) received concurrent clofazimine. 74% of participants were cured or successfully completed treatment, and outcomes did not differ by HIV status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase of 23.7 (SD 22.7) ms from baseline to month 6. Four participants experienced a QTcF\textgreater500 ms and 19 experienced a △QTcF\textgreater60 ms. Older age was independently associated with QT-prolongation. QT-prolongation was neither more common nor severe in participants receiving concurrent lopinavir-ritonavir. Conclusions: Severe QT-prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close QT-monitoring may be advisable in older patients. Keywords: Bedaquiline; HIV; QT-interval; antiretroviral therapy; clofazimine; extensively drug-resistant tuberculosis; multidrug-resistant tuberculosis.
@article{Brust2021,
abstract = {Background: Bedaquiline improves treatment outcomes in patients with rifampin-resistant TB (RR-TB) but prolongs the QT-interval and carries a black-box warning by the U.S. Food and Drug Administration. The World Health Organization recommends that all patients with RR-TB receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. Methods: We conducted an observational cohort study of RR-TB patients from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, including electrocardiograms (ECGs) performed in triplicate at four time points during bedaquiline therapy. Participants were followed until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT-prolongation, defined as any QTcF{\textgreater}500 ms or an absolute change from baseline (△ QTcF) {\textgreater}60 ms. Results: We enrolled 195 eligible participants, of whom 40{\%} had extensively drug-resistant (XDR) TB. Most participants (97{\%}) received concurrent clofazimine. 74{\%} of participants were cured or successfully completed treatment, and outcomes did not differ by HIV status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase of 23.7 (SD 22.7) ms from baseline to month 6. Four participants experienced a QTcF{\textgreater}500 ms and 19 experienced a △QTcF{\textgreater}60 ms. Older age was independently associated with QT-prolongation. QT-prolongation was neither more common nor severe in participants receiving concurrent lopinavir-ritonavir. Conclusions: Severe QT-prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close QT-monitoring may be advisable in older patients. Keywords: Bedaquiline; HIV; QT-interval; antiretroviral therapy; clofazimine; extensively drug-resistant tuberculosis; multidrug-resistant tuberculosis.},
author = {Brust, James C M and Gandhi, Neel R and Wasserman, Sean and Maartens, Gary and Omar, Shaheed V and Ismail, Nazir A and Campbell, Angela and Joseph, Lindsay and Hahn, Alexandria and Allana, Salim and Hernandez-Romieu, Alfonso C and Zhang, Chenshu and Mlisana, Koleka and Viljoen, Charle A and Zalta, Benjamin and Ebrahim, Ismaeel and Franczek, Meghan and Master, Iqbal and Ramangoaela, Limpho and te Riele, Julian and Meintjes, Graeme A},
doi = {10.1093/cid/ciab335},
file = {:C$\backslash$:/Users/Claire/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Brust et al. - 2021 - Effectiveness and cardiac safety of bedaquiline-based therapy for drug-resistant tuberculosis a prospective cohort.pdf:pdf},
issn = {1058-4838},
journal = {Clinical Infectious Diseases},
keywords = {James C M Brust,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Neel R Gandhi,OA,PROBeX Study Team,PubMed Abstract,doi:10.1093/cid/ciab335,fund{\_}ack,original,pmid:33882121},
mendeley-tags = {OA,fund{\_}ack,original},
month = {apr},
pages = {ciab335},
pmid = {33882121},
publisher = {Clin Infect Dis},
title = {{Effectiveness and cardiac safety of bedaquiline-based therapy for drug-resistant tuberculosis: a prospective cohort study}},
url = {https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab335/6244470},
year = {2021}
}
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