Mycobacterial disease · Treating rifampicin-resistant TB
A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis
| Design | Open-label, randomised, controlled non-inferiority trial, terminated early |
|---|---|
| Treatment | 24-week all-oral regimen of bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM) |
| Control | Accepted standard care for rifampicin-resistant tuberculosis |
| Population | 301 patients in stage 2 with rifampicin-resistant pulmonary tuberculosis |
| Follow-up | 72 weeks |
| Primary endpoint | Composite unfavourable outcome of death, treatment failure, treatment discontinuation, loss to follow-up or recurrence |
| Result | In the modified intention-to-treat analysis, 11% of the BPaLM group and 48% of the standard-care group had a primary-outcome event — risk difference -37 percentage points (96.6% CI -53 to -22). In the per-protocol analysis the figures were 4% and 12%. Recruitment was terminated early. The regimen also had a better safety profile. Grade 3 or higher and serious adverse events were less frequent with BPaLM than standard care, 19% versus 59%. |
| Secondary endpoints | Safety, adverse events leading to discontinuation, culture conversion |
In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile.
The trial authors, in the published abstract
A 37 percentage point absolute difference is extraordinary, and reflects how poor standard care for rifampicin-resistant tuberculosis was — 48% of the control group had an unfavourable outcome. Together with Nix-TB and ZeNix it rewrote WHO guidance and ended the era of injectable aminoglycosides.
Nyang'wa BT, Berry C, Kazounis E, et al. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med 2022 Dec 22;387(25):2331-2343.