Mary Wilson
Well-known member
February 20, 2023
DOI: 10.1056/NEJMoa2212537
Nicholas I. Paton, M.D., Christopher Cousins, M.B., Ch.B., Celina Suresh, B.Sc., Erlina Burhan, M.D., Ka Lip Chew, F.R.C.P.A., Victoria B. Dalay, M.D., Qingshu Lu, Ph.D., Tutik Kusmiati, M.D., Vincent M. Balanag, M.D., Shu Ling Lee, B.Sc., Rovina Ruslami, Ph.D., Yogesh Pokharkar, M.Sc., et al., for the TRUNCATE-TB Trial Team[SUP]*[/SUP]
Abstract
BACKGROUND
Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear.
METHODS
In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin–linezolid and bedaquiline–linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points.
RESULTS
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 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin–linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline–linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, −3.4 to 5.1; noninferiority met). 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 incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups.
CONCLUSIONS
A strategy involving initial treatment with an 8-week bedaquiline–linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns.
https://www.nejm.org/doi/full/10.1056/NEJMoa2212537
DOI: 10.1056/NEJMoa2212537
Nicholas I. Paton, M.D., Christopher Cousins, M.B., Ch.B., Celina Suresh, B.Sc., Erlina Burhan, M.D., Ka Lip Chew, F.R.C.P.A., Victoria B. Dalay, M.D., Qingshu Lu, Ph.D., Tutik Kusmiati, M.D., Vincent M. Balanag, M.D., Shu Ling Lee, B.Sc., Rovina Ruslami, Ph.D., Yogesh Pokharkar, M.Sc., et al., for the TRUNCATE-TB Trial Team[SUP]*[/SUP]
Abstract
BACKGROUND
Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear.
METHODS
In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin–linezolid and bedaquiline–linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points.
RESULTS
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 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin–linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline–linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, −3.4 to 5.1; noninferiority met). 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 incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups.
CONCLUSIONS
A strategy involving initial treatment with an 8-week bedaquiline–linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns.
https://www.nejm.org/doi/full/10.1056/NEJMoa2212537