Clinical trial results published today in the New England Journal of Medicine show that a shorter, all-oral treatment regimen for drug-resistant tuberculosis (TB) is more effective and safer than standard care.
The phase 2/3 TB-PRACTECAL trial, the results of which were initially presented in October 2021 at a conference prior to peer review, compared outcomes and adverse events in rifampicin-resistant TB patients who were randomly assigned to receive the 6-month BPaLM (bedaquiline, pretomanid, linezolid, and moxifloxacin) regimen or the 9- to 20-month standard-care regimen. Patients 15 years or older at seven sites in Belarus, South Africa, and Uzbekistan were enrolled.
The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or TB recurrence) at 72 weeks at randomization. The noninferiority margin was 12 percentage points.
The trial enrolled 552 patients, 301 of whom were included in the final analysis. In the modified intention-to-treat analysis, 7 of 62 patients (11%) in the BPaLM group had an unfavorable status at 72 weeks, compared with 32 of 66 patients (48%) in the standard-care group. With an unadjusted risk difference of –37 percentage points, the BPaLM regimen was both noninferior and superior to the standard-care treatment. The incidence of adverse events of grade 3 or higher or serious adverse events was significantly lower in the BPaLM group than in the standard-care group (19% vs 59%).
BPaLM is one of two shorter, all-oral regimens that were recently recommended by the World Health Organization for treating patients who have multidrug-resistant or rifampicin-resistant TB, based on data from TB-PRACTECAL and other trials.
"This publication will provide deeper evidence to policymakers and treatment providers deciding to use the TB PRACTECAL regimen," chief trial investigator Bern-Thomas Nyang'wa, medical director for trial sponsor Doctors Without Borders/Medecins Sans Frontieres (MSF), said in a press release. "Now it is essential that the new treatment is made available to everyone who needs it."
MSF says five countries have begun implementing the BPaLM regimen, and eight are set to implement it next year.