Article and Study Summary:

Article:

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis

Published in:

N Engl J Med. 2025;392(5):468–482. https://www.nejm.org/doi/full/10.1056/NEJMoa2400327

Authors:

Guglielmetti L, Khan U, Velásquez GE, et al.

Summary

The endTB trial was a phase 3, multinational, open-label, randomized, controlled, noninferiority trial that assessed the efficacy and safety of five 9-month, all-oral regimens for treatment of rifampin-resistant, fluoroquinolone-susceptible tuberculosis (TB) in Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa. People ≥15 years of age were enrolled if they had fluoroquinolone-susceptible, rifampin-resistant pulmonary TB and were randomized to receive standard therapy per the World Health Organization (WHO) recommendations or one of five experimental regimens using Bayesian response-adaptive randomization. The experimental regimens were administered over 39 weeks (9 months) and contained combinations of the following drugs: bedaquiline (B), delamanid (D), clofazimine (C), linezolid (L), levofloxacin (Lfx), moxifloxacin (M), and pyrazinamide (Z). The regimen combinations were BLMZ, BCLLfxZ, BDLLfxZ, DCLLfxZ, and DCMZ. The primary efficacy endpoint was a favorable outcome at week 73, defined as the absence of an unfavorable outcome and either two consecutive negative cultures or favorable bacterio­logic, radiologic, and clinical evolution. The noninferior­ity margin was set at −12 percentage points. A modified intention-to-treat population (n=699) was used for the main noninferiority analysis, and three regimens (BLMZ, BCLLfxZ and BDLLfxZ) were found to be consistently noninferior to standard therapy. There were no new safety concerns identified in the experimental groups. In August 2024, the WHO endorsed the use of these three regimens (BLMZ, BCLLfxZ and BDLLfxZ) over the longer (>18 months) regimens, expanding options for effective, simple, all-oral treatment for adults and children with this disease.

Full Synopsis:

>>>> For the full synopsis, please see the PDF version available in English. French, Spanish, and Portuguese coming soon.)

Please share your thoughts and experiences with us in the comments section below.

Discussion Questions:

1) How could the findings in this study impact policy where you work?

2) What would it take to implement the study regimens in the programs you work with? Do you have any experiences to share?

Articles of Note:

Efficacy of dolutegravir plus lamivudine in treatment-naive people living with HIV without baseline drug-resistance testing available (D2ARLING): 48-week results of a phase 4, randomised, open-label, non-inferiority trial

Safety, tolerability, and acceptability of long-acting injectable cabotegravir for HIV prevention in cisgender female adolescents (HPTN 084-01): a single-arm, open-label, phase 2b trial

Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother–infant pairs (MTN-043): a phase 3B, open-label, randomised trial

Impact of an international HIV funding crisis on HIV infections and mortality in low-income and middle-income countries: a modelling study