TRUNCATE-TB trial: Shorter Eight-week drug regimen shows promise

The trial included patients with rifampin-susceptible pulmonary tuberculosis. They were randomly assigned to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first eight weeks) or a strategy involving initial therapy with an 8-week regimen, extended treatment.

There were four strategy groups with different initial regimes; noninferiority was evaluated in the two strategy groups with complete enrollment having initial regimens of high-dose bedaquiline–linezolid and rifampin–linezolid (each with ethambutol, pyrazinamide, and isoniazid). The primary outcome was a composite of ongoing treatment, death, or active disease at 96 weeks. The noninferiority margin was 12 percentage points.

The study led to the following findings:

• Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up.
• A primary-outcome event occurred in 3.9% of the standard treatment group, as compared with 11.4% in the strategy group with an initial rifampin–linezolid regimen (adjusted difference, 7.4 percentage points; noninferiority not met) and 5.8% in the strategy group with an initial bedaquiline–linezolid regimen (adjusted difference, 0.8 percentage points).
• The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin–linezolid strategy group, and 85 days in the bedaquiline–linezolid strategy group.
• The grade 3 or 4 adverse events and serious events were similar in the three groups.

'We showed that Initial treatment with an 8-week bedaquiline–linezolid regimen was noninferior to standard treatment for TB concerning clinical outcomes," the researchers wrote. "The strategy was linked with a shorter treatment duration and with no evident safety concerns."

Reference:

The study "Treatment Strategy for Rifampin-Susceptible Tuberculosis" was published online in the New England Journal of Medicine on February 20, 2023. DOI: 10.1056/NEJMoa2212537