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v2.1.4829.produseast1

Journal Article > Protocol

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial

Patil SB, Tamirat M, Khazhidinov K, Ardizzoni E, Atger M, Austin A, Baudin E, Bekhit M, Bektasov S, Berikova E, Bonnet MMB, Caboclo R, Chaudhry M, Chavan VV, Cloez S, Coit JM, Coutisson S, Dakenova Z, De Jong BC, Delifer C, Demaisons S, Do JM, Dos Santos Tozzi D, Ducher V, Ferlazzo G, Gouillou M, Khan UT, Kunda M, Lachenal N, LaHood AN, Lecca L, Mazmanian M, McIlleron HM, Moreau M, Moschioni M, Nahid P, Osso E, Oyewusi L, Panda S, Pâquet A, Thuong Huu P, Pichon L, Rich ML, Rupasinghe P, Salahuddin N, Sanchez Garavito E, Seung KJ, Velásquez GE, Vallet M, Varaine FFV, Yuya-Septoh FJ, Mitnick CD, Guglielmetti L
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Abstract
BACKGROUND
Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients.

METHODS
endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. 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 324 participants across 2 arms affords at least 80% power to show the non-inferiority, 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.

DISCUSSION
This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen.
Countries
KazakhstanLesothoPakistanPeruViet NamIndia
Subject Area
antibiotic resistancetuberculosismodels of careantimicrobial resistance
Collections
The endTB project
DOI
10.1186/s13063-023-07701-6
Published Date
30-Nov-2023
PubMed ID
38037119
Languages
English
Journal
Trials
Volume / Issue / Pages
Volume 24, Issue 1, Pages 773
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