A four-month regimen matches standard therapy for drug-susceptible TB

Design

Multicentre, open-label, randomised, proof-of-concept, non-inferiority phase 2b/c trial

Population

121 adults with newly diagnosed drug-susceptible pulmonary TB, South Africa

Primary outcome

Sputum culture conversion at end of treatment

Effect

Pooled regimen 96.0% vs standard 100%; difference −4.0% (80% CI −7.4 to 3.4)

A proof-of-concept phase 2b/c trial at six South African sites randomised 121 adults with newly diagnosed, drug-susceptible pulmonary tuberculosis to one of three doses of a four-month, all-oral regimen of quabodepistat, delamanid and bedaquiline, or to the standard six months of rifampicin-based therapy.

End-of-treatment sputum culture conversion was 96.0% with the pooled new regimen against 100% with standard care, meeting the non-inferiority margin (difference −4.0%, 80% CI −7.4 to 3.4). Grade 3 or higher adverse events were somewhat more common on the new regimen (11–20% across doses) than on standard therapy (5%), though none of the serious events were attributed to the trial drugs.

For a country carrying a large share of the world's tuberculosis, a shorter all-oral course would matter enormously — but this is early. The endpoint is culture conversion at the end of treatment, a surrogate for cure rather than durable, relapse-free outcome, and quabodepistat is investigational and not available. It is a signal to run the larger trial, not to change regimens.

• A four-month quabodepistat-delamanid-bedaquiline regimen was non-inferior to six months of standard therapy for culture conversion.
• Culture conversion was 96% with the new regimen versus 100% with standard care.
• Higher-grade adverse events were more frequent on the new regimen than on standard therapy.
• Treat this as a proof-of-concept signal, not a reason to shorten any patient's regimen now.

Why it matters

Shortening drug-susceptible TB treatment from six to four months would ease a huge burden — if a larger trial confirms durable cure.

Don't overread it

The endpoint is end-of-treatment culture conversion, a surrogate — it does not yet show the regimen prevents relapse, and the trial was small and open-label.

The statistics, in plain English

Non-inferiority within an 80% confidence interval is a weaker bar than the usual 95%, and culture conversion predicts but does not equal cure, so a positive result here is a reason to test further, not to adopt.

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