A MAJOR trial assessing shortened tuberculosis treatments has found that, while some 8-week drug combinations are promising, they remain less effective than the current standard therapy.
The TRUNCATE-TB trial was a multi-arm, multi-stage, open-label randomised controlled study designed to test the efficacy and safety of 8-week regimens for treating rifampicin-susceptible pulmonary tuberculosis in adults aged 18–65 years. Participants were randomised to receive either the WHO-recommended 24-week standard regimen or one of four novel 8-week regimens, all of which included five drugs with variations in rifampicin dosage or substitutions such as bedaquiline, linezolid, clofazimine, or rifapentine. The regimens were part of the broader TRUNCATE strategy, which includes post-treatment monitoring and re-treatment where needed. Efficacy, defined as the proportion with an unfavourable outcome (mainly relapse), and safety were analysed using Bayesian methods in an intention-to-treat population.
A total of 674 participants were included in the analysis, with two of the four regimens progressing to full enrolment. Unfavourable outcomes occurred in 4% (7/181) of those receiving standard treatment. This rose to 25% (46/184) in the high-dose rifampicin and linezolid group, with an adjusted difference of 21.0% (95% Bayesian credible interval [BCI]: 14.3–28.1), and 14% (26/189) in the bedaquiline and linezolid group (adjusted difference 9.3% [BCI: 4.3–14.9]). Safety outcomes showed Grade 3–4 adverse events in 14% of the standard group, 11% of the high-dose rifampicin-linezolid group, and 12% of the bedaquiline-linezolid group, indicating comparable tolerability across regimens.
While shortened regimens may offer logistical and adherence advantages, they currently show higher relapse rates than standard treatment. Even the most promising 8-week option, bedaquiline with linezolid, should be considered only within a structured management strategy, including close monitoring and the option for re-treatment.
Reference
Paton NI et al; TRUNCATE-TB Trial Team. Efficacy and safety of 8-week regimens for the treatment of rifampicin-susceptible pulmonary tuberculosis (TRUNCATE-TB): a prespecified exploratory analysis of a multi-arm, multi-stage, open-label, randomised controlled trial. Lancet Infect Dis. 2025; DOI:10.1016/S1473-3099(25)00151-3.
