Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial. Guglielmetti, L, Ardizzoni, E, Atger, M, Baudin, E, Berikova, E, Bonnet, M, Chang, E, Cloez, S, Coit, J M, Cox, V, de Jong, B C, Delifer, C, Do, J M, Dos Santos Tozzi, D, Ducher, V, Ferlazzo, G, Gouillou, M, Khan, A, Khan, U, Lachenal, N, LaHood, A N, Lecca, L, Mazmanian, M, McIlleron, H, Moschioni, M, O'Brien, K, Okunbor, O, Oyewusi, L, Panda, S, Patil, S B, Phillips, P P J, Pichon, L, Rupasinghe, P, Rich, M L, Saluhuddin, N, Seung, K J, Tamirat, M, Trippa, L, Cellamare, M, Velásquez, G E, Wasserman, S., Zimetbaum, P J, Varaine, F, & Mitnick, C D Trials, 22:651, BioMed Central, sep, 2021. ![Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.
@article{Guglielmetti2021,
abstract = {Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80{\%} power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12{\%}, against the control in both modified intention-to-treat and per protocol populations. The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.},
author = {Guglielmetti, L and Ardizzoni, E and Atger, M and Baudin, E and Berikova, E and Bonnet, M and Chang, E and Cloez, S and Coit, J M and Cox, V and de Jong, B C and Delifer, C and Do, J M and {Dos Santos Tozzi}, D and Ducher, V and Ferlazzo, G and Gouillou, M and Khan, A and Khan, U and Lachenal, N and LaHood, A N and Lecca, L and Mazmanian, M and McIlleron, H and Moschioni, M and O'Brien, K and Okunbor, O and Oyewusi, L and Panda, S and Patil, S B and Phillips, P P J and Pichon, L and Rupasinghe, P and Rich, M L and Saluhuddin, N and Seung, K J and Tamirat, M and Trippa, L and Cellamare, M and Vel{\'{a}}squez, G E and Wasserman, Sean and Zimetbaum, P J and Varaine, F and Mitnick, C D},
doi = {10.1186/S13063-021-05491-3},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Guglielmetti et al. - 2021 - Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB) study protocol for an adaptive.pdf:pdf},
issn = {1745-6215},
journal = {Trials},
keywords = {Biomedicine,Health Sciences,Medicine,Medicine/Public Health,OA,OA{\_}PMC,Statistics for Life Sciences,fund{\_}not{\_}ack,general,protocol},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,protocol},
month = {sep},
pages = {651},
pmid = {34563240},
publisher = {BioMed Central},
title = {{Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial}},
url = {https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05491-3},
volume = {22},
year = {2021}
}
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