Six-month regimen matches nine months for drug-resistant TB in South African trial

Drug-resistant tuberculosis has long meant longer, harsher treatment. A pragmatic phase 3 trial in South Africa has now tested whether a six-month, all-oral regimen can do the job of the nine-month standard-of-care — and found that it can, matching cure rates with a similar safety profile [s1]. The result, from the BEAT Tuberculosis trial published in the New England Journal of Medicine, is the kind of finding that shortens treatment for the people who find it hardest to complete [s1].

The trial

BEAT Tuberculosis was an open-label, pragmatic, randomized, controlled non-inferiority trial conducted in South Africa in people aged 6 years or older with pulmonary rifampicin-resistant tuberculosis [s1]. Participants were assigned either to a six-month regimen of bedaquiline, linezolid, delamanid, and levofloxacin or clofazimine or both — the trial-strategy group — or to the 9-month standard-of-care regimen that was then current in South Africa [s1].

"Pragmatic" is the operative word. The trial deliberately kept its population close to real-world clinics: people who were pregnant or breastfeeding and those with fluoroquinolone-resistant tuberculosis were included, and treatment in both groups was adjusted on the basis of second-line drug-susceptibility testing [s1].

The primary efficacy endpoint was a successful outcome — cure or completion of treatment — measured at the end of treatment and at 76 weeks after randomization, with a non-inferiority margin of 10 percentage points [s1]. The primary safety endpoint was an adverse event of grade 3 or higher [s1].

What it found

Among 432 people screened, 403 underwent randomization: 203 to the six-month trial strategy and 200 to the nine-month control [s1].

The two regimens were essentially tied. A successful outcome was observed in 174 of 202 participants (86.1%) in the trial-strategy group and in 172 of 200 (86.0%) in the control group [s1]. The adjusted risk difference was -0.2 percentage points (95% CI -6.9 to 6.5; P=0.001 for non-inferiority) — comfortably inside the pre-set 10-point margin [s1].

Safety was comparable, and if anything numerically favoured the shorter regimen. Grade 3 or higher adverse events during treatment occurred in 63 of 202 participants (31.2%) in the trial-strategy group and 74 of 200 (37.0%) in the control group [s1]. Ten participants died in each group [s1].

Why a shorter regimen matters

The burden the trial addresses is large and stubborn. WHO counts 1.23 million tuberculosis deaths in 2024 and an estimated 10.7 million people falling ill, and describes multidrug-resistant TB as a continuing public-health crisis and health-security threat [s2]. Crucially, only about 2 in 5 people with drug-resistant TB accessed treatment in 2024 [s2]. When treatment is long, toxic and hard to complete, fewer people finish it — and every month trimmed off a regimen lowers the barrier to a cure.

Three months shorter, with equivalent cure and no safety penalty, is therefore not a marginal convenience. It means less time on multiple drugs, fewer clinic visits, and a regimen that programmes can realistically deliver to more of the people currently going untreated. The all-oral composition also avoids the injectable agents that defined older drug-resistant TB regimens, which were associated with hearing loss and required repeated clinic attendance for administration.

The regimen tested here builds on a now-familiar backbone. Bedaquiline and linezolid anchor most modern drug-resistant TB regimens, and delamanid and a fluoroquinolone round out the combination the trial used [s1]. The pragmatic design is as important as the drugs: by enrolling pregnant and breastfeeding women and people with fluoroquinolone resistance — groups often excluded from registration trials — BEAT Tuberculosis tested the strategy in close to the full spectrum of patients a national programme actually treats, and adjusted therapy to drug-susceptibility results rather than holding every participant to one fixed regimen [s1]. That makes the result more directly transferable to routine care, even as it leaves open how each individual component contributed.

The limits

This was a single-country trial, conducted in South Africa, and its control arm was the nine-month regimen current there rather than every standard used elsewhere [s1]. Non-inferiority trials answer a specific question — is the new approach not meaningfully worse? — rather than whether it is superior, and the point estimate here was a statistical tie, not an improvement [s1]. The 403 randomized participants make this a moderately sized trial, enough to clear the margin but not to resolve rarer outcomes [s1]. The equal death toll of ten in each group is a reminder that drug-resistant TB remains dangerous even under trial conditions [s1].

What to watch

Whether national and WHO treatment guidelines move to adopt a six-month option for rifampicin-resistant disease on the strength of results like these, and whether the regimen holds up in other settings and health systems [s1]. The direction of travel in drug-resistant TB has been toward shorter, all-oral regimens; BEAT Tuberculosis adds pragmatic, randomized evidence that the shortening can be done without giving up the cure.

This article is informational and does not constitute medical advice.

Sources

• A Pragmatic Trial of a 6-Month Strategy for Rifampicin-Resistant Tuberculosis — New England Journal of Medicine, 25 June 2026
• Tuberculosis — Fact sheet — World Health Organization