TRUNCATE-TB trial: Shorter Eight-week drug regimen shows promise
Singapore: Findings from a randomized trial have shown that a strategy involving initial treatment with an 8-week regimen of high bedaquiline and linezolid doses is noninferior to the standard, 6-month rifampin-based tuberculosis (TB) treatment concerning clinical outcomes, with no evident safety concerns.
According to results of the multicenter TRUNCATE-TB trial, truncating the duration of treatment to 2 months using a bedaquiline-linezolid regimen was noninferior to the standard 6-month regimen in patients with pulmonary tuberculosis (TB) in terms of clinical outcomes.
In the study, published in the New England Journal of Medicine, the researchers mentioned the participants' responses that were more motivated to adhere to the initial course of 8 weeks than the standard treatment.
A 6-month rifampin-based regime is the standard treatment for tuberculosis. However, there needs to be more clarity on whether a strategy involving shorter initial treatment may provide similar outcomes. Considering this, Nicholas I. Paton from Yong Loo Lin School of Medicine in Singapore and colleagues compared a standard 6-month rifampin-based TB treatment to a strategy involving shorter initial treatment with extended therapy for persistent clinical disease, monitoring and retreatment for relapse in an adaptive, open-label, noninferiority trial.
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
