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v2.1.4829.produseast1

Journal Article > Research

Nine-month, all-oral regimens for rifampin-resistant tuberculosis

Guglielmetti L, Khan U, Velasquez GE, Gouillou M, Abubakirov A, Baudin E, Berikova E, Berry C, Bonnet M, Cellamare M, Chavan V, Cox V, Dakenova Z, de Jong BC, Ferlazzo G, Karabayev A, Kirakosyan O, Kiria N, Kunda M, Lachenal N, Lecca L, McIlleron H, Motta I, Mucching-Toscano S, Mushtaque H, Nahid P, Oyewusi L, Panda S, Patil S, Phillips P, Ruiz J, Salahuddin N, Sanchez-Garavito E, Seung KJ, Ticona E, Trippa L, Vargas D, Wasserman S, Rich ML, Varaine F, Mitnick CD
Abstract

BACKGROUND

After a history of poor treatments for rifampin-resistant tuberculosis (RR-TB), recent advances have resulted in shorter, more effective treatments. However, they are not available to everyone and have shortcomings, requiring additional treatment options.


METHODS

endTB is an international, open-label, Phase 3 non-inferiority, randomized, controlled clinical trial to compare five 9-month all-oral regimens including bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C) and pyrazinamide (Z), to the standard (control) for treatment of fluoroquinolone-susceptible RR-TB. Participants were randomized to 9BLMZ, 9BCLLfxZ, 9BDLLfxZ, 9DCLLfxZ, 9DCMZ and control using Bayesian response-adaptive randomization. The primary outcome was favorable outcome at week 73 defined by two negative sputum culture results or by favorable bacteriologic, clinical and radiologic evolution. The non-inferiority margin was 12 percentage points.


RESULTS

Of 754 randomized patients, 696 and 559 were included in the modified intention to treat (mITT) and per-protocol (PP) analyses, respectively. In mITT, the control had 80.7% favorable outcomes. Regimens 9BCLLfxZ [adjusted risk difference (aRD): 9.5% (95% confidence interval (CI), 0.4 to 18.6)], 9BLMZ [aRD: 8.8% (95%CI, −0.6 to 18.2)], and 9BDLLfxZ [3.9% (95%CI, −5.8 to 13.6)] were non-inferior in mITT and in PP. The proportion of participants experiencing grade 3 or higher adverse events was similar across the regimens. Grade 3 or higher hepatotoxicity occurred in 11.7% of the experimental regimens overall and in 7.1% of the control.


CONCLUSIONS

The endTB trial increases treatment options for RR-TB with three shortened, all-oral regimens that were non-inferior to a current well-performing standard of care.

Countries
GeorgiaKazakhstanLesothoPakistanPeruSouth AfricaIndia
Subject Area
antibiotic resistancetuberculosisantimicrobial resistance
Collections
New tools and approaches to drug-resistant TBThe endTB project
DOI
10.1101/2024.01.29.24301679
Published Date
29-Jan-2024
Languages
English
Journal
medRxiv
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