Use of an initial 8-week tuberculosis treatment strategy and continued use if ineffective is non-inferior to the standard 6-month regimen
Shorter tuberculosis treatment courses in those with rifampin susceptible disease involving an initial 8-week course containing bedaquiline and linezolid is non-inferior to the standard regimen, with respect to clinical outcomes, according to the TRUNCATE-TB trial investigators.
According to the World Health Organisation, in 2021, globally, an estimated 10.6 million people contracted tuberculosis, leading to an estimated 1.6 million deaths. Currently, treatment of drug susceptible pulmonary tuberculosis requires a 6-month rifampin-based regimen although this can affect adherence and ultimately lead to treatment failure. However, emerging evidence suggests that a 4-month rifapentine-based regimen containing moxifloxacin was non-inferior to the standard 6-month regimen. In the current study, researchers wondered if an initial 8-week treatment regimen, which could be extended for persistent clinical disease with follow-up after treatment and prompt re-treatment for those who relapse, may be as effective as the current standard regimen.
The Two-Month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-Sensitive Tuberculosis (TRUNCATE-TB) trial, compared whether an initial regimen of either high-dose rifampin-linezolid or bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol) was non-inferior to the current standard regime of rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks. Individuals were randomised to either the standard regime or a strategy of an 8-week regimen (rifampin-linezolid or bedaquiline-linezolid) with extended treatment if required. The primary outcome was a composite of death, ongoing treatment, or active disease at week 96 and the non-inferiority margin set at 12%.
Tuberculosis treatment strategy outcomes
A total of 674 participants were included and randomised to the different strategies.
The primary outcome event occurred in 3.9% of those in the standard regime and 11.4% in the rifampin-linezolid regimen (adjusted difference, AD = 7.4%, 95% CI 1.7 – 13.2%), hence non-inferiority was not met. In contrast, the primary outcome occurred in 5.8% of those assigned to bedaquiline-linezolid regimen (AD = 0.8%, 95% CI -3.4 to 5.1%), hence the criterion for non-inferiority (12%) was met with this regimen.
In fact, the mean total duration of treatment was 180 days in the standard-treatment group but only 85 days in the bedaquiline-linezolid strategy group, with a similar incidence of grade 3 or 4 adverse and serious events across the three groups.
The authors concluded that use of an 8-week regimen with bedaquiline-linezolid proved to be non-inferior to the standard regimen and with no apparent safety concerns.
Paton NI et al. Treatment Strategy for Rifampin-Susceptible Tuberculosis. N Eng J Med 2023