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The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens

BACKGROUND: At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability...

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Autores principales: Khan, Uzma, Huerga, Helena, Khan, Aamir J., Mitnick, Carole D., Hewison, Catherine, Varaine, Francis, Bastard, Mathieu, Rich, Michael, Franke, Molly F., Atwood, Sidney, Khan, Palwasha Y., Seung, Kwonjune J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701145/
https://www.ncbi.nlm.nih.gov/pubmed/31429722
http://dx.doi.org/10.1186/s12879-019-4378-4
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author Khan, Uzma
Huerga, Helena
Khan, Aamir J.
Mitnick, Carole D.
Hewison, Catherine
Varaine, Francis
Bastard, Mathieu
Rich, Michael
Franke, Molly F.
Atwood, Sidney
Khan, Palwasha Y.
Seung, Kwonjune J.
author_facet Khan, Uzma
Huerga, Helena
Khan, Aamir J.
Mitnick, Carole D.
Hewison, Catherine
Varaine, Francis
Bastard, Mathieu
Rich, Michael
Franke, Molly F.
Atwood, Sidney
Khan, Palwasha Y.
Seung, Kwonjune J.
author_sort Khan, Uzma
collection PubMed
description BACKGROUND: At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens. METHODS: This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries. DISCUSSION: The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments. TRIAL REGISTRATION: This study was registered on 24 August 2017 at clincaltrials.gov (Registration number: NCT03259269). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4378-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-67011452019-08-26 The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens Khan, Uzma Huerga, Helena Khan, Aamir J. Mitnick, Carole D. Hewison, Catherine Varaine, Francis Bastard, Mathieu Rich, Michael Franke, Molly F. Atwood, Sidney Khan, Palwasha Y. Seung, Kwonjune J. BMC Infect Dis Study Protocol BACKGROUND: At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens. METHODS: This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries. DISCUSSION: The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments. TRIAL REGISTRATION: This study was registered on 24 August 2017 at clincaltrials.gov (Registration number: NCT03259269). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4378-4) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-20 /pmc/articles/PMC6701145/ /pubmed/31429722 http://dx.doi.org/10.1186/s12879-019-4378-4 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Khan, Uzma
Huerga, Helena
Khan, Aamir J.
Mitnick, Carole D.
Hewison, Catherine
Varaine, Francis
Bastard, Mathieu
Rich, Michael
Franke, Molly F.
Atwood, Sidney
Khan, Palwasha Y.
Seung, Kwonjune J.
The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
title The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
title_full The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
title_fullStr The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
title_full_unstemmed The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
title_short The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
title_sort endtb observational study protocol: treatment of mdr-tb with bedaquiline or delamanid containing regimens
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701145/
https://www.ncbi.nlm.nih.gov/pubmed/31429722
http://dx.doi.org/10.1186/s12879-019-4378-4
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