A six-month, all-oral treatment strategy for rifampicin-resistant TB (RR-TB) achieved outcomes comparable to longer standard therapy in a pragmatic phase 3 trial conducted in South Africa, according to findings published in The New England Journal of Medicine.1 The results may expand treatment options for patients who have historically faced prolonged, burdensome regimens and could be particularly important for children and pregnant patients, populations often underrepresented in TB drug trials.1
The BEAT Tuberculosis trial enrolled 403 patients with pulmonary RR-TB, including people living with HIV, those who were pregnant or breastfeeding, and patients with fluoroquinolone-resistant disease. Participants were randomly assigned to receive either a six-month regimen consisting of bedaquiline, linezolid, delamanid, and levofloxacin or clofazimine (or both), or the current standard of care regimen in South Africa, which generally lasts nine months or longer.
Investigators led by Francesca Conradie, MB, BCh, of the Isango Lethemba TB Research Unit at the University of the Witwatersrand, Gqeberha, South Africa, designed the study as a noninferiority trial, with successful treatment defined as cure or treatment completion at the end of therapy and sustained through 76 weeks after randomization.
A successful outcome was achieved by 86.1% of patients in the six-month treatment group and 86.0% of those receiving standard therapy. The adjusted risk difference was -0.2 percentage points (95% CI, -6.9 to 6.5), meeting the trial’s predefined noninferiority criterion.
The investigators concluded that the findings show a shorter treatment strategy could achieve outcomes similar to those of longer standard regimens.
Study investigator Patrick PJ Phillips, PhD, Associate Professor of Biostatistics at the University of California, San Francisco at the Center for Tuberculosis, said one of the more striking findings was the overall success rate achieved in a study designed to closely reflect routine clinical practice.
“Despite this being a pragmatic trial with broad eligibility criteria—only 6.7% of participants screened were not enrolled—and many aspects of patient management and trial procedures embedded within routine care, the proportion of participants with a successful outcome was high,” Dr. Phillips said. “The broad eligibility of the trial means that the results have wide generalizability, and this is reflected in the [World Health Organization] recommendations that are not as restrictive as some other TB regimen recommendations.”
Importantly, Dr. Phillips noted that the efficacy appeared consistent across major subgroups, including HIV status and fluoroquinolone susceptibility, although the trial was not powered to detect subgroup-specific differences.
Safety outcomes were also similar between the treatment arms. Grade 3 or higher adverse events during treatment occurred in 31.2% of patients receiving the six-month regimen, and 37.0% of those receiving standard therapy. Ten participants in each group died during treatment or follow-up. Investigators found no meaningful differences across major safety end points.
As expected, linezolid-related toxicity remained a significant concern. Anemia was the most common serious adverse event and frequently required temporary treatment interruption; some patients required blood transfusions. Peripheral neuropathy and optic neuropathy also occurred, leading to permanent discontinuation of linezolid in a minority of participants.
“This is a challenge with current [drug-resistant] TB linezolid-based regimens,” Dr. Phillips said. “Linezolid is the drug that is targeted for replacement in ongoing and future clinical trials of new drugs.”
Despite these toxicities, most patients receiving the experimental regimen completed the planned 24 weeks of therapy. Among those who completed treatment, nearly 80% did so without interruptions in study drug dosing.
Beyond the clinical outcomes, the shorter regimen could make a substantial difference for patients.
“A six-month standardized treatment strategy that is suitable for both [fluoroquinolone]-resistant and [fluoroquinolone]-susceptible TB means that patients can start treatment as soon as the [rifampin] resistance result becomes available and can finish treatment much sooner than the older nine- or 18-month regimens.”
The findings may be particularly relevant in populations for whom pretomanid-containing regimens are not currently recommended. The delamanid-based strategy evaluated in the study was designed to provide an alternative for such populations. All enrolled participants younger than 18 years achieved successful outcomes, and all pregnancies resulted in live births.
References
1. Conradie F, Badat T, Poswa A, et al. A pragmatic trial of a 6-month strategy for rifampicin-resistant tuberculosis. N Engl J Med. 2026;394(24):2429-2439. doi:10.1056/NEJMoa2503687
